© American Academy of Pain Medicine 1526-2375/02/$15.00/172 172–190

18th Annual AAPM Meeting Abstracts

PAIN MEDICINE

Volume 3

•

Number 2

•

2002

Clinical Research

24-HOUR APPLICATION OF THE LIDOCAINE PATCH 5% FOR 3 CONSECUTIVE DAYS IS SAFE AND WELL TOLERATED IN HEALTHY ADULT MEN AND WOMEN

Arnold R. Gammaitoni, PharmD, Endo Pharmaceuticals, Chadds Ford, PA; Nancy A. Alvarez, PharmD, Endo Pharmaceuticals, Chadds Ford, PA

Objective:

To determine the tolerability and evaluatethe pharmacokinetics and safety of continuous 24-hourapplication of the lidocaine patch 5% (Lidoderm®), asite-specific general analgesic that relieves pain by reduc-ing peripheral nociceptive impulse generation.

Background:

The lidocaine patch 5% currently has anFDA-approved indication for the treatment of posther-petic neuralgia (maximum dose: 3 patches for 12 h/d). Arecent study reported no significant safety findings, labo-ratory abnormalities, or adverse effects of 4 lidocainepatches applied for an 18-hour period on 3 consecutivedays. The present study was designed to determine thesafety and tolerability of 4 patches applied for 24 hourseither once daily or every 12 hours on 3 consecutive days.

Methods:

In this open-label study, 20 healthy subjectswere randomized to apply 4 patches either QD or BIDto the upper back for 3 consecutive days. Plasma druglevels, local anesthetic effect, and occurrence of adverseeffects were evaluated.

Results:

The maximal plasma lidocaine concentrationswere 212.3 and 231.0 ng/mL for the QD and BID regi-mens, respectively, representing approximately 1/6 thelevel required for cardiac activity (1500 ng/mL) and 1/20that for toxicity (5000 ng/mL). Adjusted area under thecurve values were 4099.8 and 4703.5 ng

�

h/mL and half-life values were 6.8 and 7.9 hours with QD and BID use,respectively. Sensory examination (light touch and pinprick) revealed no loss or alteration of sensation at theapplication site in any subject. Erythema, which oc-curred in 14 subjects and was very slight (n

�

12) tomoderate (n

�

2), did not result in any discontinuations.There were no reports of edema at any application sitesthroughout the study. No reports of systemic adverseevents related to study medication were noted.

Conclusions:

Continuous 24-hour application of 4lidocaine patches produced plasma lidocaine levels wellbelow those associated with cardiac activity/toxicity.There was no reported alteration in sensation at any ap-plication site, demonstrating that continuous 24-hourapplication of the lidocaine patch 5% still did not pro-duce a local anesthetic effect in the skin underlying patch

application. Both dosing regimens (4 patches QD andBID) were well tolerated and no systemic adverse eventsrelated to the study medication were reported.

Research

THE END-STAGE CANCER PATIENT: A DESCRIPTIVE ANALYSIS OF FINAL LONG-ACTING OPIOID DOSE DISTRIBUTION AMONG HOSPICE PATIENTS

Susannah Hall, ExcelleRx Inc., Rollin M. Gallagher, MCP Hahnemann School of Medicine, Calvin Knowlton, ExcelleRx Inc., Terri Maxwell, Thomas Jefferson University, and Douglas Weschules, ExcelleRx, Inc

A long-acting opioid is often the cornerstone of the anal-gesic regimen for hospice patients. The final weeks oflife may be associated with increased analgesic needs re-lated to disease progression and the effective titration oflong-acting opioids can be crucial to the enhancement ofquality of life for these patients. A large range of opioiddoses is reported in the literature for this population.This analysis will describe the distribution of final long-acting opioid doses among a population of these pa-tients. This is a retrospective analysis of all hospice pa-tients with the primary diagnosis of cancer admitted to aNorth American palliative care specialty pharmacy be-tween 4/1/00 and 3/31/01. The final opioid dose was de-fined as the last long-acting opioid prescription writtenprior to death. Patients who were prescribed sustainedrelease oral morphine or oxycodone or transdermal fen-tanyl were included in the analysis. A total of 7201 pa-tients met the inclusion criteria for the analysis. At thetime of death, 30.1% of the morphine SR patients and24.9% of the oxycodone SR patients were prescribedoral long-acting opioid doses that were lower than thelowest available transdermal fentanyl product. Morphineequivalent doses

�

120mg/day were prescribed for67.2% of patients. Morphine equivalent doses

�

300mg/day were prescribed for 9.7% of patients with 3.9% ofpatients prescribed doses

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600mg/day. Age, but notgender, was independently associated with morphineequivalent dose. A descriptive analysis of primary cancersite within subpopulations will be presented, includingthose patients prescribed

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600mg/day (N

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280).

Research (clinical or experimental)

A MULTI-CENTER TRIAL OF PERCUTANEOUS NEUROMODULATION THERAPY FOR LOW BACK

Abstracts

173

PAIN PATIENTS WITH A SUBACUTE DURATION OF LOWER EXTREMITY PAIN

Joseph Condon, MD, Southern California Orthopedic Institute; Joanne Borg-Stein, MD, Spaulding Rehabilitation-Wellesley; John Revord, MD, NeuroSpine Center of Wisconsin; Susan Schmitt, MD, The Everett Spine Center; Jerel Glassman, DO, St. Mary’s Hospital and Spine Center; Elizabeth Bensen, MD, Agnesian Healthcare; Eric Leep, DO, Hastings Orthopedic Clinic; Jeffery Fitzthum, MD, Northwest Hospital; Richard Seroussi, MD MSc; Bradford Fowler, MSc, Vertis Neuroscience.

Introduction:

We performed a prospective multi-centertrial of percutaneous neuromodulation therapy (PNT)for low back pain patients (LBP) with a subacute durationof radiating pain. PNT is a more standardized method ofdelivering percutaneous electrical stimulation, previouslyvalidated for chronic LBP patients in randomized, con-trolled crossover trials [JAMA 1999; 281:818–23].

Methods:

Our study involved a multi-center study with83 enrolled patients. Patients were recruited from clini-cal practice or advertisement, with inclusion criteria of:1) buttock and/or leg pain duration of 1–6 months, and2) pain intensity of at least 4/10 on a visual analog scale(VAS). PNT was administered once a week for at least 4weeks, and consisted of 30-minute sessions with the pa-tient prone, receiving electrical stimulation through 5percutaneous electrode pairs deployed 3 centimeters intothe lumbar paraspinal tissues. Outcome measures in-cluded VAS scores for pain, sleep and activity, as well asan Oswestry Disability Questionnaire.

Results:

At 5-week follow-up, leg/buttock pain scoresimproved from 6.6

�

1.7 to 4.0

�

2.6 (p

�

0.001), activ-ity levels improved from 6.0

�

2.2 to 3.6

�

2.2 (p

�

0.001), sleep scores improved from 4.8

�

3.0 to 3.1

�

2.5 (p

�

0.001), and Oswestry scores improved from 43

�

15 to 33

�

16 (p

�

0.001). 63% of patients had

�

30%improvement in leg/buttock pain scores.

Conclusion:

PNT appears promising for treating LBPpatients with a subacute duration of radiating pain.November 16, 2001.

Clinical (includes case reports)

ANALGESIC USE, PAIN EXPERIENCE, AND HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH OSTEOARTHRITIS OF THE HIP AND/OR KNEE PRESCRIBED ORAL OPIOID ANALGESICS

Gale Morrissey-Harding, MA,

1

Daniel A. Ollendorf, MPH,

1

Ellen Dukes, PhD,

2

Deborah Hoffman, PhD,

2

Erin G. Richardson, BA,

1

Gerry Oster, PhD

1

1

Policy Analysis, Incorporated,

2

Pudue Pharma LP

Background:

Analgesic use, pain experience, and health-related quality of life among patients with osteoarthritisof the hip and/or knee who have been prescribed oralopioid analgesics have not been well characterized. Weexamined these issues in a patient survey.

Methods:

Study subjects were patients with osteoarthri-tis of the hip and/or knee who had been prescribed oralopioid analgesics; they were recruited from the offices ofa random sample of US internists and family practitio-ners. Data were collected via mail survey. Measures ofinterest included dosage, frequency, and duration of useof oral opioids and other analgesic medications, pain in-tensity and interference with activities, and satisfactionwith pain medication, and health-related quality of life asassessed on a standard 100 point utility thermometer.

Results:

A total of 229 patients returned completed sur-veys. Study subjects reported moderate to severe levelsof pain and interference with activities, and low levels ofhealth-related quality of life. Approximately one-third(31%) reported that they were not currently using opi-oids; among remaining patients, only 9% of patients re-ported using a long-acting opioid. Use of over-the-counter (OTC) pain relievers was widespread. One-thirdof those who reported using an OTC pain reliever con-taining acetaminophen also took prescription productscontaining acetaminophen.

Conclusions:

Many patients with osteoarthritis of thehip and/or knee who have been prescribed oral opioidanalgesics nonetheless report significant pain, activity in-terference, and impaired quality of life. Our findings sug-gest that the prescribing of an opioid analgesic is not afinal step in pain management; continued medical man-agement is needed to ensure acceptable health outcomes.

BOTULINUM TOXIN TYPE A (BOTOX®) IN THE TREATMENT OF REFRACTORY MYOFASCIAL CERVICOTHORACIC PAIN: A PROSPECTIVE TRIAL

Dorene Taqi, Ian Gunyea, PA-C, Bhadresh Bhakta, MD, Venkatesh Movva, MD, Sameh Ward, MD, Mike Jenson, PA-C, CPP, Mike Royal, MD

Pain Evaluation and Treatment Center, 5801 East 41

st

Street, Suite 1000, Tulsa, OK 74135(918) 622-3888; fax: (918) 828-9050; email: royal@tulsapain.com

Myofascial pain syndrome (MPS) is a common chronicpain syndrome defined by the presence of trigger pointsand referred pain (Travell, Simons, 1983). A prospectivestudy of patients with MPS involving the upper trapeziusand levator scapulae muscles refractory to conservativetherapy was performed to evaluate the effects of volumeof diluent used with Botulinum toxin Type A (BT

A

,Botox®, Allergan, Inc., Irvine, CA). A total of 90 pa-tients are planned in this double-blind, prospective trial,

174

Abstracts

however only 45 have completed the 24 week observa-tion period. We have not broken the blind, but wish toreport interim prospective data on responses to BT

A

. Allpatients who entered had only short-term responses totrigger point injections and were randomized to threevolume groups (200u/cc, 100u/cc and 50u/cc in saline).Algometry, tenderness, spasm scores, VAS scores, McGillshort form pain questionnaire scores, and global re-sponses were followed at 2, 4, 6, 8, 12, and 24 weeks.The injections were performed as trigger point injec-tions by palpation directly into the trigger point with25u/site. The total patient dose was 75–150 units for 3–6trigger points into the affected muscles. Global re-sponses were graded on a 4- to 4

scale. Pressure algo-metry was performed in the standard fashion. Musclespasm and tenderness was graded on a 4 point scale. Ofthe 45 patients, 33 were responders with at least a 1

subjective response and 23/45 showed at least a 3

re-sponse lasting for 24 weeks. Algometry scores nearlydoubled in this group and significant drops in McGill,tenderness, spasm and VAS scores were seen as well.The injections were well tolerated with no significantside effects noted. Botulinum toxin injection appears tobe a promising method for managing refractory MPS.

Travell JG, Simons DG.

Myofascial pain and dysfunction:the trigger point manual. Vol. I.

Baltimore, MD: Williams& Wilkins; 1983.

BOTULINUM TOXIN TYPE B (MYOBLOC™) IN THE TREATMENT OF REFRACTORY MYOFASCIAL PAIN

Dorene Taqi, Ian Gunyea, PA-C, Bhadresh Bhakta, MD, Venkatesh Movva, MD, Sameh Ward, MD, Mike Jenson, PA-C, CPP, Mike Royal, MD

Pain Evaluation and Treatment Center, 5801 East 41

st

Street, Suite 1000, Tulsa, OK 74135(918) 622-3888; fax: (918) 828-9050; email: royal@tulsapain.com

Myofascial pain syndrome (MPS) is a common chronicpain syndrome defined by the presence of trigger pointsand referred pain (Travell, Simons, 1983). Myobloc™(Botulinum toxin type B [BTB], Elan Pharmaceuticals)was FDA-approved last year for the treatment of cervicaldystonia. A retrospective review of 32 patients who re-ceived BTB for treatment of refractory MPS was per-formed. These data were added to an additional 8 pa-tients who received BTB in a prospective fashion as partof a phase I study evaluating BTB in lower back myofas-cial pain. Forty patients (32 retrospective, 8 prospective;25F: ages 34–78y/15M: ages 35–81y) received BTB in-jections into affected muscles, e.g., cervical/thoracic (22),lumbar (12), and piriformis (6). The injections were per-formed as standard trigger point injections by palpation

using Myobloc™ 500–2500 units/site in 0.5–2 ml (0.5%bupivacaine was used to dilute to the desired concentra-tion). Patients received up to 18,000 units total dose. Pa-tient global response rates, McGill short form pain ques-tionnaire, VAS scores and side effects were monitored.No significant side effects were noted. Response to in-jection was defined as poor (

�

30% symptom reduction),fair (30–49% reduction), good (50–69% reduction), andexcellent (

�

70% reduction). Twenty-three patients re-ported good (12/40) to excellent (11/40) pain relief last-ing an average of 3.3 months. An additional 8 patientsreported fair responses. During the response phase, thepatients who responded well to Myobloc™ were able totolerate a more aggressive therapeutic exercise program.Controlled prospective trials of BTB in myofascial painwould be desirable.

Travell JG, Simons DG.

Myofascial pain and dysfunction:the trigger point manual. Vol. I.

Baltimore, MD: Williams& Wilkins;1983.

The prospective study was supported by a research grantfrom Elan.

Clinical

BOTULINUM TOXIN TYPE B INJECTION FOR A PATIENT WITH MYOFASCIAL PAIN

Howard Smith, Joseph Audette, Ranjan Dey, Sajid Khan, Zahid Bajwa

Beth Israel Deaconess Medical CenterBoston, MA

Botulinum toxin type B (BoNT-B; Myobloc) has beenproven safe and effective for managing patients with cer-vical dystonia. The basis for the effectiveness of botuli-num toxin in dystonic conditions is related to its abilityto produce a localized paralysis in injected muscles. Thismechanism as well as other potential theoretical mecha-nisms may be responsible for its effectiveness in provid-ing significant and prolonged pain relief in these pa-tients. We treated a 38-year old female with myofascialpain with BoNT-B. The patient presented with chronicupper back/neck, bilateral shoulder pain, and occasionalmild frontal headaches that has been ongoing for thepast 12 years. The pain was reported to worsen with ac-tivities but was better with rest. Physical examinationfindings include: 7/10 for pain severity; trigger points inthe neck and upper back; mild decrease in range of mo-tion (ROM) in the neck; full ROM elsewhere. Past andpresent interventions include physical therapy/TENS,diazepam, nortriptyline, baclofen, Tylenol with codeine,tramadol, and motrin. We initiated the patient onBoNT-B injections, 5000 U divided equally over fivesites (1000 U/0.2 cc). Efficacy was determined by pa-

Abstracts

175

tient’s assessment of pain and ROM. Overall, the resultsof treatment with BoNT-B in our patient with myofas-cial pain were very good. At the 3-month follow-up, thepain was decreased to 2/10 and patient had full ROM.The patient experienced no complications, reported noadverse effects, and was overall very satisfied with thetreatment. It is conceivable that BoNT-B may be usefulfor the treatment of myofascial pain; further studies arewarranted. The mechanisms of action of muscle paralysisas well as analgesia for BoNT-B will be discussed and il-lustrated. A review of the literature will be presentedalong with other clinical situations in which BoNT-Bmay be worthwhile investigating. Support of Elan Phar-maceuticals is gratefully acknowledged.

Research (clinical)

CATEGORICAL VERSUS CONTINUOUSMEASURES OF PAIN: IMPLICATIONS FOR COMMUNITY-BASED RESEARCH

Jana Mossey, PhD, MSN, and Rollin M. Gallagher, MD, MPH, MCP Hahnemann University

Introduction:

The Parmelee adaptation of the McGillPain Questionnaire (PAMPQ), widely used in studies ofelderly, creates values ranging between 5 (‘no pain’) and25 (‘severe pain’). The scale, when treated as a continu-ous measure, is statistically efficient but difficult to inter-pret for values between 6 and 24. In longitudinal studies,change scores are conveniently calculated as the differ-ence between two consecutive pain assessments. Therange of change scores for the PAMPQ,

20 to

20,denotes direction of change but clinical ambiguity.Categorical classification provides an alternative. Usingtwo PAMPQ items tapping current pain and pain-relatedactivity limitations, individuals can be classified as: 1) Nopain; 2) pain without activity limitations; and 3) painwith activity limitations. The clarity of this three-levelmeasure is intuitively appealing. Change in pain can beidentified by cross-classifying individuals at consecutiveassessments, although these measures may mask smallchanges and restrict analytic options.

Method:

Longitudinal data on 353 community dwellingelders, based on the PAMPQ, permitted us to comparethe ability of categorical and continuous pain measuresto characterize cross-sectional pain levels and changeover two years.

Results:

Categorical cross-sectional analyses classifiedindividuals as: (1) no pain (41%); (2) pain without limita-tions (23%); and (3) pain with activity limitations (36%).Additional analyses showed statistically significant meandifferences between groups 1, 2 & 3 on the continuousform of PAMPQ. Substantial score overlaps occurredbetween pain groups (2 & 3): each had 51% with scores

between 10 and 16, making interpretation of individualscores difficult. Longitudinal comparisons revealed simi-lar difficulty.Continuous difference scores ranged from

19 to 16(mean .849; sd 4.639). Most experiencing a 2 levelchange on the pain classification variable had differencescores

�

(

/

4). Comparable change occurred in 45%changing 1 pain level and 25 % with no change.

Discussion

: These findings highlight differences be-tween continuous and categorical pain measures, withimplications for pain research.

Clinical

COMPLICATION RATE ASSOCIATEDWITH FACET JOINT RADIOFREQUENCY DENERVATION PROCEDURES

Craig A. Kornick, M.D., S. Scott Kramarich, M.D., B. Todd Sitzman, M.D., M.P.H., Kenneth A. Marshall, M.D., Juan Santiago-Palma, M.D., Tim J. Lamer, M.D.

Division of Pain Management, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224

Introduction:

Radiofrequency (RF) neural lesioning,also known as RF denervation or neurotomy, is a widelyutilized treatment for chronic cervical, thoracic and lum-bar facet joint-related back pain. Major complicationsare rare when facet joint RF neural lesioning protocolsare strictly adhered to. The objective of this study was todetermine the complication rate associated with facetjoint RF neural lesioning in patients undergoing theseprocedures at Mayo Clinic Jacksonville.

Methods:

Following Mayo Clinic IRB approval, com-plete data were collected using a retrospective chart re-view of all patients undergoing facet joint RF denerva-tion procedures over a five-year period (1996–2001). AllRF lesions were performed using a RFG-3CF LesionGenerator (Radionics, Inc.; Burlington, MA), utilizing astandardized lesioning protocol. An insulated 22G, 10cm Sluijter-Mehta cannula with a 5-mm active tip(SMK-C10; Radionics, Inc.) was placed near the ana-tomic target site (i.e., medial branch nerve of the dorsalprimary ramus innervating the target facet joint) usingfluoroscopic guidance. The RF electrode (RadionicsSMK-TC) was then inserted. When sensory stimulation(up to 1 volt at 50 Hz) and motor stimulation (up to 5volts at 2 Hz) failed to produce nerve root-mediated sen-sory and motor manifestations, RF lesioning (80

�

C for90 seconds) was performed. Post-procedural assessmentwas routinely performed through telephone follow-up in3 to 5 days and a scheduled return visit in 4 to 6 weeks.Data were recorded in a computerized data base and in-cluded: patient demographics, RF denervation level, to-tal number of RF lesions per patient, date of first return

176

Abstracts

visit, and presence of RF complication, if any. Types ofcomplications recorded included: local pain (includingmyofascial, symptomatic hematoma, non-neuritic) at RFsite

�

1 week duration, neuritic pain

�

2 weeks, neuriticpain

�

2 weeks, infection, new motor deficit, and newsensory deficit. The chart of every patient with post-RFcomplaints was reviewed and adjudicated by a panel offour physicians before being classified as a complication.Descriptive statistical analysis was performed and re-ported as mean

�

standard deviation and percentages.

Results:

A total of 629 RF denervation lesions, involving122 separate operative procedures, were performed on95 patients. Mean patient age was 66

�

13 years, with54% female. Each patient received on average 5

�

3 RFlesions per operative procedure (range 2 to 16). Facetjoint spinal levels involved were primarily lumbar (95%),followed by cervical (3%) and thoracic (2%). Mean re-turn visit follow-up was at 36 days. A total of 10 compli-cations were noted among 8 separate operative proce-dures, yielding an overall complication rate of 6.5% peroperative procedure. Complications included: 2 cases ofneuritic-type pain lasting

�

2 weeks, 5 with neuritic-typepain at RF site lasting

�

2 weeks, 2 with prolonged local-ized pain (non-neuritic), and 1 with prolonged musclespasm at the RF operative site. There were no reports ofinfection, new sensory deficits, or new motor deficits.

Conclusion:

Facet joint RF denervation procedures, whenperformed using appropriate lesioning protocol tech-niques, are associated with a 6.5%

minor

complication rate.

Clinical

CONTROLLED-RELEASE OXYCODONE RELIEVES MODERATE TO SEVERE PAIN IN A 3-MONTH STUDY OF PERSISTENT MODERATE TO SEVERE BACK PAIN

Patricia Richards, MD, PhD; Pinggao Zhang, PhD; Michael Friedman, PhD; Rahul Dhanda, PhD. (Purdue Pharma L.P.)

Introduction:

Opioids are frequently prescribed formanagement of persistent low back pain, however, effi-cacy has not been well documented, and concerns arethat opioids may impair physical functioning.

Objective:

To compare controlled-release oxycodone(CRO) with placebo in controlling pain and to observethe effect of CRO on quality of life and functionality.

Methods:

A double-blind, randomized, placebo-con-trolled, parallel-group study of 3 months duration wasconducted in 110 subjects (49 males, 61 females), meanage 48 years (19–80 years). Subjects had a 3- to 12-month history of moderate to severe persistent low backpain and were previously unresponsive to therapeuticdoses of NSAIDs, and/or low dose combination opioid

analgesics. At baseline 4% of subjects were on opioids,39% on NSAIDs, and 57% both NSAIDs and opioids.Subjects were treated with 10 mg CRO tablet or 10 mgoral placebo q12h, titrated to stable pain control. Exist-ing treatment regimens of acetaminophen, NSAIDs, ororal steroids were allowed to continue. The Brief PainInventory (BPI), the Roland Morris Functionality Ques-tionnaire, and the MOS 36-Item Short-Form HealthSurvey (SF-36) were the measures of pain intensity,functionality, and quality of life. Treatments were com-pared using repeated measures ANCOVA with baselinevalue as covariate.

Results:

CRO treatment was significantly superior to pla-cebo on the BPI average pain intensity and average percentpain relief scores overall (4.6 vs 5.4,

P

�

.03, and 47.2 vs36.3,

P

�

.05, respectively). Fewer CRO subjects discon-tinued because of inadequate pain control (

P

�

.001). Nosignificant differences between treatments were observedin either Roland Morris or SF-36 scores. Common adverseevents for CRO were nausea, constipation, somnolence,headache, and pruritus, consistent with opioid use.

Conclusions:

Three-month treatment with CRO pro-vides significant pain relief for subjects with persistentmoderate to severe back pain, without significantly im-pairing functionality and quality of life.

The support of Purdue Pharma L.P. for this researchproject is gratefully acknowledged.

Clinical

DICHOTOMY OF CORTICAL PAIN PROCESSING

Jahangir Maleki, Rollin M. Gallagher, Pain Medicine and Rehabilitation Center, MCP/Hahnemann School of Medicine

Introduction:

Functional MRI and PET studies of cor-tical pain processing indicate segregated pain pathwaysabove the thalamus. Although experimental pain may re-sult in multiple areas of altered cortical activity, it is pos-tulated that thalamic pain fibers known as the lateral sys-tem, projecting to sensory cortex, serve to localize pain,whereas medial pathways projecting to limbic cortex,process affective aspects of pain.

Case Study:

A 27 y/o female, with left upper extremitypain and severe allodynia from Complex Regional PainSyndrome, Type I (CRPS I / RSD), after receiving intra-pleural bupivacaine blocks developed an ipsilateral focal-onset secondary generalized tonic clonic seizure. Thiswas followed by one hour of post-ictal confusion. Simul-taneously she developed a dense left-sided motor andsensory deficit (Todd’s palsy) with a motor deficit resolv-ing in one day whereas a sensory deficit lasted 2 days.Throughout the duration of the sensory deficit she de-nied any left arm pain, although she continued to report

Abstracts

177

the same intensity of pain, but now localized to her epi-gastric region. Interestingly, despite the lack of sensoryperception on the left side, palpation of her left arm re-sulted in increased epigastric pain and suffering.

Discussion:

This case indicates a bifurcation of the painpathway between the thalamus and cortex. Due to focalseizure activity, the sensory cortex (i.e. lateral system)was transiently rendered dysfunctional, during whichtime the continued presence of pain and allodynia with-out appropriate localization likely resulted from pain con-duction, from the thalamus to functional limbic struc-tures such as Cingulum (i.e. via the medial fibre system).

Conclusion:

This case report strongly supports the hy-pothesis of medial and lateral pain conducting fibersbranching at the level of thalamus with medial sub-serv-ing the emotional aspects of pain by projection to limbiccortex, whereas lateral fibres project to sensory cortex,primarily serving a localizing function.

Clinical

DULOXETINE: A POTENTIAL NEWTREATMENT FOR DEPRESSED PATIENTS WITH COMORBID PAIN

David Goldstein, MD PhD; Smriti Iyengar, PhD; Craig Mallinckrodt, PhD; Yili Lu, PhD; Michael Detke, MD PhD; Mark Demitrack, MD

Eli Lilly & Company, Lilly Corporate Center, Indianapolis, IN 46285Pain is commonly comorbid with major depressive disor-der (MDD), but assessment of pain has been neglected instudies of MDD. Serotonin (5-HT) and norepinephrine(NE) have been implicated in both MDD pathophysiologyand analgesia mediated by descending pain pathways inbrain and spinal cord. Duloxetine hydrochloride is a potentand balanced reuptake inhibitor of 5-HT and NE. Atdoses consistent with 5-HT and NE reuptake inhibition invivo, recent animal studies have demonstrated duloxetineto be efficacious in reducing persistent and neuropathicpain. In the present double-blind, placebo-controlled clini-cal trials, the analgesic efficacy of duloxetine was assessedin patients with MDD using visual analogue scales. Inthese trials, duloxetine demonstrated statistically signifi-cant superiority to placebo on primary efficacy measures inthe treatment of depressed mood symptoms in MDD pa-tients and was superior to paroxetine on most efficacy out-comes. Moreover, duloxetine demonstrated significant su-periority over placebo in reducing overall pain severity, aswell as other pain measures, in patients with MDD. Du-loxetine was well tolerated, with dry mouth, headache, in-somnia, somnolence, and sweating as the most commonlyreported treatment-emergent adverse events. Collectively,these data suggest that duloxetine, a potent and balanced

reuptake inhibitor of 5-HT and NE, is a safe and effica-cious new treatment for MDD with comorbid pain.

Research

EFFICACY OF THE SELECTIVE SEROTONIN AND NOREPINEPHRINE REUPTAKE INHIBITOR, DULOXETINE, IN THE FORMALIN MODEL OF PERSISTENT PAIN

Smriti Iyengar, PhD; Frank Bymaster, MS; David Wong, PhD; Rosa Simmons, PhD; Laura Ahmad, PhD

Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, U.S.ASerotonin (5-HT) and norepinephrine (NE) are impli-cated in enhancing endogenous analgesic mechanismsvia descending inhibitory pain pathways in the brain andspinal cord. In vivo microdialysis studies have shown thatduloxetine is a potent and selective 5-HT and NE re-uptake inhibitor in brain. This study evaluated the ef-fects of duloxetine and other agents on late phase paw-licking behavior in the formalin model of persistent painin rats. Intrathecal, intracisternal, or intraperitoneal ad-ministration of duloxetine significantly attenuated for-malin-induced late phase paw-licking behavior in a dose-dependent manner. Duloxetine was more potent thanvenlafaxine, another dual 5-HT/NE reuptake inhibitor,in its ability to reverse formalin-induced late phase paw-licking behavior. Additionally, the reversal of late phaseformalin-induced behavior by amitriptyline and de-sipramine (other drugs used in the clinical managementof pain) occurred at doses that also caused neuromuscu-lar dysfunction in the rotorod test, in contrast to dulox-etine which demonstrated full effect at doses that did notcause neuromuscular dysfunction. Low doses of the se-lective 5-HT reuptake inhibitor paroxetine and the se-lective NE reuptake inhibitor thionisoxetine alone didnot have an effect in the formalin test, however, whencombined, showed significant effects on attenuating for-malin-induced late phase paw-licking behavior. Thesedata are consistent with the proposed role of 5-HT andNE in being key mediators of descending pain pathways.Moreover, 5-HT and NE reuptake inhibition by dulox-etine may offer a highly effective and safe alternative fortreatment of persistent pain states in man.

Clinical

EPIDUROGRAPHY: CHARACTERISTICS OF EPIDURALGRAMS PERFORMED DURING LESI

David C. Miller MD, DABPM Woodland Pain Center, Michigan City, INFluoroscopically guided, contrast enhanced lumbar epi-dural steroid injections are commonly performed for

178 Abstracts

persistent or sever lumbar radicular pain. An epidural-gram is a real-time fluoroscopic image of contrast in-jected into the epidural space prior to the injection of lo-cal anesthetic and steroid. This report details the resultsof one hundred consecutive epiduralgrams. The epiduralneedle was placed under continuous multiplainer fluoro-scopic guidance using ISIS protocol. Three ml. of Om-nipaque 300 were injected after initial insertion to obtainthe epiduralgram. This was followed by injection of 3ml. of Celestone diluted with 4 ml. of preservative-free1% lidocaine to obtain the epiduralgram. The epiduralneedle was placed at the predetermined spinal level andappropriate side 100% of the time. Needles were suc-cessfully placed into the epidural space on the first at-tempt in 95%. One needle was subarachnoid, one wasintra vascular, three were in tissue plains superficial tothe epidural space and were apparent only with contrastinjection. Three ml. of contrast flowed unilaterally in74% of lumbar epidural injections. The contrast flowedcephalad only in 20%, caudad only in 28%, and bidirec-tional in 52%. Contrast spread less than three spinal lev-els 64% of the time. The desired nerve root was visual-ized in 62%. Contrast was seen in the ventral epiduralspace on lateral views 88% of the time. Ventral spreadwas always fewer levels than the dorsal spread. Epi-durography provides essential information for the accu-rate performance of lumbar epidural steroid injections.One out of every twenty presumed epidural injectionswere inaccurately placed even by an experienced opera-tor. One out of every fifty was dangerously positionedand identified only by performance of an epiduralgram.

Clinical

EVALUATION OF BOTULINUM TOXIN TYPE B (MYOBLOC) FOR MYOFASCIAL PAIN: RESULTS OF A PRELIMINARY PATIENT SURVEY

Patrick N. Rhoades, MD

Stanislaus Center for Fitness and Optimal HealthBotulinum toxin type B (Myobloc; BoNT-B) is indicatedfor the treatment of cervical dystonia. The toxin pre-vents acetylcholine release presynaptically at the neuro-muscular junction, producing a dose-dependent degreeof paralysis in injected muscles. This effect has beenfound to alleviate symptoms, including pain associatedwith cervical dystonia, and suggests that BoNT-B maybe useful for the treatment of other painful conditions.We treated six patients (2 male; 4 female) with myofas-cial pain syndrome with BoNT-B injections (total dose5000–10,000 U), and report of the results of a follow-uptelephone survey conducted 4 to 16 weeks post-injec-tion. The four female patients had pain in the neck/shoulders and were injected in that region. The two male

patients were injected in the lower back muscles. Thesurvey included questions about the severity of pain pre-and post-injection (0–10 numeric rating scale), range ofmotion (ROM), need for use of pain medications, andchange in functioning. The severity of pain pre-injectionaveraged about 7/10. All patients had a very positive re-sponse to treatment. Following BoNT-B injection, painseverity decreased an average of 3.1/10. 5/6 patientshad improvements in ROM, and 4/6 patients reported adecrease in number of pain medications needed. Therewere improvements in the ability to perform certain ba-sic tasks (eg, brushing teeth) as well as other activities(eg, running). Overall, BoNT-B was well-tolerated.Some patients experienced flu-like symptoms that sub-sided after about 1 week. All patients indicated thattreatment was very helpful and would be interested in re-ceiving a re-injection. Our preliminary findings supportfurther investigation of BoNT-B in the treatment of my-ofascial pain. Support of Elan Pharmaceuticals is grate-fully acknowledged.

Clinical

EVALUATION OF MYOBLOC (BOTULINUMTOXIN TYPE B) IN PATIENTS WITHPOST-WHIPLASH HEADACHES

Ciceron L. Opida, MD, Bon Secour Holy Family Hospital of Altoona

Altoona, PAMyobloc (botulinum toxin type B; BoNT-B) is a newbotulinum toxin serotype antigenically distinct from thetype A toxin. It acts to block the release of acetylcholineat the neuromuscular junction, resulting in a localizedparalysis when minute doses are injected. Studies in pa-tients with cervical dystonia have shown that BoNT-Beffectively reduces symptoms including pain associatedwith this disorder, and suggest that it may be effective inalleviating other painful syndromes, such as chronicheadaches. The purpose of this open-label study was toevaluate the efficacy of BoNT-B in the treatment of pa-tients with post-whiplash headaches. Thirty-one patientswere enrolled in the study. These patients were statuspost-whiplash after 6 months, had headaches that weredisabling after 4 weeks of injury, and were complainingof deep head pain that was radiating from the occipital tothe orbital and lasting for more than 5-months duration.Patients had restriction of head flexion, rotation, and/orside bending at the top of the neck. The numeric ratingscale (0–10) was used to rate the severity of symptoms.Pre-injection, most patients were at 10 on the NRS;none were below 8. Patients were injected with 1 ccBoNT-B (5000 U) divided among the suboccipital mus-cles (Recti capitis posteriors major and minor, obliqui

Abstracts 179

capitis inferior and superior). Of the 31 patients, 22(71%) reported improvements in their headache inten-sity and severity, and neck motion. Most patients were at0–2 on the NRS post-injection. Adverse effects were mi-nor, consisting mainly of dry mouth (40%) and pain atthe injection site lasting for only a few days. The resultsof our study suggest that BoNT-B may be an effectiveagent for the treatment of post-whiplash headaches; fur-ther studies are warranted. Support of Elan Pharmaceu-ticals is gratefully acknowledged.

Clinical Research

FLUOROSCOPIC AND ELECTROMYOGRAPHIC GUIDED INJECTION OF THE PIRIFORMIS MUSCLE WITH BOTULINUM TOXIN TYPE B

Paul V. Beck, BS1, Gagan Mahajan, MD1, Barth L. Wilsey, MD1,2, Paul G. Kreis, MD1, and Scott M. Fishman, MD1

Analgesic Research Program: 1Division of Pain Medicine, University of California, Davis 2Northern California Veterans Administration Pain ClinicsPiriformis syndrome (PS) is possibly an under-diagnosedform of buttock and leg pain involving irritability of thesciatic nerves, presumably related to effects from theoverlapping piriformis muscle. Spasm, inflammation, andhypertrophy of the muscle may compress the sciaticnerve, either between the muscle and the bony pelvis, orbetween inflamed fascicles of the muscle itself (Durraniand Winnie, 1991.) Injection of the muscle can be diffi-cult. We have developed a novel technique for needleguidance (Fishman et al 1999). Using an injectable 4–6inch EMG needle, we use EMG to locate the muscle im-mediately posterior to the ischium followed by fluoros-copy with radiopaque dye injection to confirm needleplacement in the piriformis muscle. This technique canbe used to deliver therapeutic drugs such as local anes-thetics and corticosteroids. Since piriformis spasm is aproposed mechanism for PS and recent reports have in-dicated superior efficacy for botulinum toxin injectionover corticosteroid in certain forms of myofascial painincluding PS (Porta, 2000), we have designed a test ofbotulinum toxin in PS. Several botulinum neurotoxinshave been isolated, but until recently, only botulinumtoxin type A (BOTOX™) has been available for this in-dication. Botulinum toxin type B (MYOBLOC™) is nowavailable for clinical uses. Since botulinum toxin type Boffers greater stability and ease of use (requires no re-constitution, stable at room temperature, stable withshaking/turbulence during injections etc), we chose it asthe active agent in this trial of 10 patients. We use a ran-domized placebo controlled enriched enrollment model.Patients are required to have been diagnosed with PS by

standard diagnostic criteria as well as have had tempo-rary relief from previous fluoroscopy guided piriformisinjection with local anesthetics with corticosteroid. Fivepatients are randomized to receive the placebo arm andfive to receive the active Botulinum Toxin Type B. Datacollection is ongoing and will be reported.

Clinical Research

IMPACT OF FENTANYL SHORTAGE ON POSTOPERATIVE EPIDURAL ANALGESIA: AN OUTCOME ANALYSIS

Senthilkumar Sadhasivam, Balachundhar Subramaniam, Vimal Akhouri, Carolyn Debeauport, Thomas Simopoulos, Christine Peeters-Asdourian, Robert I. Cohen. Arnold Pain Center, Beth Israel Deaconess Medical Center, Harvard Medical SchoolA nation-wide shortage of fentanyl increased the use ofepidural hydromorphone for postoperative analgesia inour hospital. Compared to fentanyl, the more hydro-philic hydromorphone is expected to achieve diffuse andmore than segmental analgesia. We aimed to evaluatethe analgesic efficacy and cost to manage postoperativepain with epidural fentanyl and hydromorphone. Withinstitutional approval, 1002 adult surgical in-patientswho required postoperative epidural analgesia (EA) werestudied. This retrospective review is based on the acutepain consultation and daily pain team follow-up reports,and chart review. The demographic data for age, genderand ASA status were comparable. The distribution ofcatheter placements was comparable [upper thoracic(T1-T6) (23% vs. 24%), lower thoracic (T6-T12) (54%vs. 49%) and lumbar (T12-L5) (23% vs. 27%) epiduralcatheters in the fentanyl and the hydromorphone respec-tively]. 525 patients received fentanyl 4�g/cc with 0.1%bupivacaine (F-group) and 477 patients received hydro-morphone 20�g/cc with 0.1% bupivacaine (H-group)epidurally. For the 757 patients with successful epiduralanalgesia who did not require supplementation with IV-PCA, the success rate was 75.4% and 75.7% respectivelyfor the F and the H groups. The success rate increased to96.0% and 95.2% for the F and the H groups when IVPCA analgesia was added (If IV-PCA started, epiduralsolution changed to bupivacaine 0.1% without opiate forboth groups). The percentage of patients who requiredIV-PCA was similar in the F- (20.6%) and the H-groups(19.5%, p�0.67). The mean rate of epidural analgesicinfusion was statistically lower in the H-group than in theF-group. The number of mean effective epidural analgesicdays was comparable in the F- and the H-groups. (Table)The number of surgically placed catheters was 21 (4%)(F) and 30 (6.3%) (H), comparable in both the groups(p�0.100). The success rate for surgically placed catheters

180 Abstracts

was comparable in the F- (67%) and the H- (73%) groups(p�0.607). The average cost per patient for the F- groupwas $23.4 and for the H- group was $22.5. Epidural hy-dromorphone has successfully taken over the place ofepidural fentanyl in the postoperative pain managementat our institution with comparable efficacy and safety.Epidural hydromorphone is as cost effective as fentanylin managing postoperative pain and with the fentanylshortage over, has remained the preferred analgesic solu-tion because of lower incidence of side effects (34% vs.42%, p�0.012).

Research (clinical)

INADEQUATE PAIN CARE FOR ELDERS: THE NEED FOR A PRIMARY CARE–PAIN MEDICINE COMMUNITY COLLABORATION

Rollin M. Gallagher, MD, MPH and Jana Mossey, PhD, MSN, MCP Hahnemann UniversityIntroduction: We conducted a 24 month longitudinalstudy of elderly with excellent healthcare access to inves-tigate the myth that pain is an inevitable consequence ofgrowing older, diminishing the importance of its treat-ment.Methods: Psychosocial and physical functioning, illnesslevel and pain (adaptation of the McGill Pain Question-naire) were measured in 232 older retirement commu-nity residents at 5 consecutive 6 month intervals. 185who completed at least 4 assessments were classified as:“no pain”; “pain without activity limitations”, or “painwith activity limitations”.Results: Only 2 (1.08%) denied pain at all assessments;conversely, 150 (64.7%) reported pain, with or withoutactivity limitations, at each assessment. 67 (36%) wereconsidered in the Chronic Pain (CP) group (CPG) by re-porting pain at each assessment and indicating at 3 ormore assessments that pain limited activities. The CPGdid not differ from those without CP in age, gender,schooling, marital status, social support and social ad-justment. CP individuals reported more medical con-

ditions, poorer physical function, and more depression.Although �80% of the CPG reported regular pain med-ication use, 65–75% described pain at its worst as “quite”to “extremely” bothersome at each assessment, and 25–48% said pain limited activities “quite a bit” or “ex-tremely”—all these figures indicate ineffective treat-ment. 42 (78%) reported pain at the same 2 or more sitesat every assessment.Discussion: The high prevalence (36%) of activity-lim-iting CP in elderly with excellent access to healthcare islikely conservative compared to rates in less affluent eld-erly. Several approaches appear promising. CP patientstypically make more physician visits—in our study, theCPG reported 1.33 times more. PCP gatekeepers can ef-fectively manage a large proportion of the elderly in painbut must be supported by pain medicine and communityrehabilitation services with appropriate access, educa-tion, mentoring programs.

Research

INTRATHECAL ZICONOTIDE EFFECT ON NEUROPATHIC SYMPTOMS AND POTENTIAL FOR ADJUNCTIVE USE WITH OPIATES: A RETROSPECTIVE REVIEW IN 25 PATIENTS

Dorene Taqi, Ian Gunyea, PA-C, Bhadresh Bhakta, MD, Venkatesh Movva, MD, Sameh Ward, MD, Mike Jenson, PA-C, CPP, Mike Royal, MD

Pain Evaluation & Treatment Center, Tulsa, OKAn ongoing, open-label, multicenter clinical trial to as-sess the long-term safety and tolerability of intrathecally(IT) administered ziconotide to patients with chronic,severe pain was initiated in November, 1998. As part ofthis study, we evaluated 52 patients with chronic intrac-table pain on IT ziconotide. Ziconotide is an N-type,voltage-sensitive calcium channel blocker with provenefficacy as an IT analgesic. In this trial, IT ziconotidewas initiated at a dose of 0.1mcg/hr, followed by long-term ziconotide infusion with titrations as needed within

Table Epidural Analgesia

Fentanyl Hydromorphone P-value

Total patients (%) 525 (52.4) 477 (47.6)# Half concentration opiate 2 28Successful EA (%) 396 (75.4) 361 (75.68) 0.926IV-PCA supplementing EA (%) 108 (20.6) 93 (19.5) 0.671Successful analgesia (%) 504/525 (96) 454/477 (95.2) 0.526Functional epidural/Failed analgesia (%) 21 (4) 23 (4.8) 0.526Mean infusion rate 9.6�2.2 8.8�2.1 �0.001*Epidural Analgesic days 3.3�1.5 3.1�1.3 0.080Initiate half concentration opioid (%) 2 (0.4) 29 (6.1) �0.001*Switch half concentration opioid (%) 6 (1.1) 25 (5.2) �0.001*

* Statistically significant for p � 0.05

Abstracts 181

study parameters. Efficacy was assessed using a visual an-alog scale. Of our 52 patients, 25 had primarily neuro-pathic pain symptoms and were on ziconotide for at least3 months. Following the change in IT therapy, 25 pa-tients were queried during the course of their treatmentwith ziconotide as to its effect on their neuropathicsymptoms (dysesthesia, allodynia, paresthesia, radiculo-pathic symptoms etc.) and queried after discontinuing zi-conotide, which was primarily due to adverse eventsfrom uptitration to cover any nociceptive pain compo-nent, on the relative effectiveness of their current ITopiate to IT ziconotide on their neuropathic symptomsand on their willingness to go back on lower dose zi-conotide with their present IT opiate in an attempt tomore effectively manage neuropathic symptoms. Most ofthe patients (18/25) observed that the neuropathic symp-toms improved at lower doses of ziconotide, but whenuptitration of dose was done to cover more of their pain,side effects occurred causing eventual discontinuation.These patients also observed that their IT opiate was lesseffective on these same neuropathic symptoms. Twenty-one of the 25 patients (84%) said they would like to tryziconotide with their opiate and 18 (72%) of them werequite sure that their neuropathic symptoms improveddramatically with the ziconotide at a dose much lowerthan their termination dose. Studies of low dose IT zi-conotide with morphine (and other opiates) are neededto determine if the risk-benefit of ziconotide-basedtreatment can be enhanced with IT drug combinations.

Clinical Research

LIDOCAINE PATCH 5% TREATS ALL NEUROPATHIC PAIN QUALITIES: RESULTS OF A RANDOMIZED CLINICAL TRIAL USING THE NEUROPATHIC PAIN SCALE

Bradley S. Galer, MD, University of Washington School of Medicine, Department of Neurology and Anesthesiology; Seattle, WA; Mark P. Jensen, PhD, University of Washington, Department of Rehabilitation Medicine, Seattle, WA; Tina Ma, PhD, Endo Pharmaceuticals, Inc, Department of Medical Affairs, Chadds Ford, PA; Pamela S. Davies, RN, MS, UCSF Pain Clinical Research Center, San Francisco, CA; Michael C. Rowbotham, MD, UCSF School of Medicine, Department of Clinical Neurology and Anesthesia, San Francisco, CAObjective: To assess the effect of the lidocaine patch5% (Lidoderm®) on distinct neuropathic pain qualities.Background: The lidocaine patch 5%, the only FDA-approved drug for the treatment of postherpetic neural-gia, is a site-specific general analgesic that relieves neu-ropathic pain by reducing peripheral nociceptive impulse

generation. Data from a vehicle-controlled trial were an-alyzed using the Neuropathic Pain Scale (NPS), whichwas designed to assess distinct pain qualities associatedwith neuropathic pain.Design/Methods: The NPS was administered to all 150subjects during a randomized, vehicle-controlled, clini-cal trial at baseline and at the end of the 3-week treat-ment period. Only patients with moderate-to-severepain at baseline (pain intensity �4/10 in at least 6 of the10 NPS items) were included in the analyses. In all, 96patients met these criteria and were included in the anal-yses.Results: The results demonstrated the statistical superi-ority of the lidocaine patch 5% compared with the vehi-cle patch as measured by: “NPS 10 Score,” a sum scoreincluding all 10 numeric NPS items (P � .043); “NPS 8Score,” a standardized average score of all 8 pain de-scriptors excluding “unpleasantness” and “global inten-sity” (P � .042); “NPS NA Score,” a standardized aver-age score of all 8 nonallodynic items (P � .022); and“NPS 4 Score,” a standardized average score of the painqualities not thought to be primarily related to periph-eral dermal pathophysiologic events, ie, “sharp,” “hot,”“dull,” and “deep” pains (P � .013).Conclusions: The lidocaine patch 5% was statisticallysuperior to the vehicle patch in reducing the intensity ofall common neuropathic pain qualities and may be effec-tive in neuropathic pain states when allodynia may notbe a prominent feature. This study further validates theNPS as a sensitive measure of treatment effects in ran-domized clinical trials.

Clinical Cases

MEDICAL-LEGAL CASES IN PAIN MANAGEMENT EMPHASIZE THE NEED FOR “STANDARD OF CARE” GUIDELINES FOR PAIN SPECIALISTS AS WELL AS PRIMARY CARE GIVERS

John H. Eisele Jr., MD and Scott M. Fishman, MD

Division of Pain Medicine, Department of Anesthesiology and Pain Management, University of California Davis, Sacramento, CA.Legal issues in pain management have historically beenrelated to over-prescribing or inappropriate prescribingof narcotics and other CNS-acting drugs. However, re-cently a case was adjudicated against a physician for notadequately treating reported pain. Complaints regardingpain practice come to the State Medical Board from phy-sicians, pharmacists, nurses, and from patients or pa-tients’ families. The complaints are usually issues ofhealth and safety or competence and/or negligence. Re-cently CA published guidelines for assessing and treatingchronic pain, however, they are not directed at pain

182 Abstracts

practitioners, particularly those who become overzealousin the application of new treatments. We present fourcases (A-D) that raise significant and common questionsregarding what is and is not prudent and acceptable care.Each of these cases is taken from requested reviews ofcommunity pain practices that are involved in legal ac-tions against them.Case A deals with the management of narcotics and adju-vant drugs in a demanding patient with failed back sur-gery syndrome, and who demonstrates behaviors consis-tent with addiction. This case emphasizes the importanceof setting clear guidelines for narcotic administration.Case B covers the practice of frequent office-based injec-tions of multiple trigger-points for myofascial pain, andthe associated use of multiple drug administrations in theoffice, both IM and IV, including narcotics. This casehighlights the signs of excessive intervention and the po-tential for reinforcing pain and pain behavior throughoffice visits for emergency analgesic treatments.Case C concerns the use of multiple and frequent invasiveprocedures in a chronic back pain patient who has mini-mal evidence of structural damage. This case under-scores the difficulties intrinsic to evaluating procedureswhen multiple blocks/injections are performed simulta-neously.Case D represents an aggressive treatment of a chronicmigraine headache with multiple narcotics, including acontinuous intra-thecal infusion. This case stresses theneed to carefully evaluate whether risks outweigh bene-fits when treatments become repetitive and unorthodox.As pain specialists, we must be able to reflect on our ownstandards of care, determine what is acceptable manage-ment and what is not, and self regulate or risk becomingfurther regulated.

Clinical

MEMANTINE IN THE TREATMENT OF DIABETICS WITH PAINFUL PERIPHERAL NEUROPATHY: A PLACEBO-CONTROLLED PHASE IIB TRIAL

Louis C. Kirby, MD: Peoria, AZ; The Memantine Study GroupInjured peripheral nerves induce the release of excitatoryamino acids in the dorsal horn of the spinal cord, causingexcitation of N-methyl-D-aspartate (NMDA) receptors.Continuous stimulation of NMDA receptors by C-fiberinput leads to central facilitation. The critical role ofNMDA receptors in the wind-up process suggests thatthey are a final common pathway for the induction ofneuropathic pain. Memantine, a moderate-affinity, un-competitive NMDA receptor antagonist, has been shownto reduce pain responses in rodent and primate chronicpain models. The objective of this 8-week multicenter,

randomized, dose-ranging, double-blind, placebo-con-trolled trial was to determine the analgesic efficacy andsafety of memantine in diabetic patients with painful pe-ripheral neuropathy (PPN). A total of 421 PPN patientsparticipated in the study (placebo n�86, 20 mg/day me-mantine n�171, 40 mg/day memantine n�164). Partici-pants had a pain visual analog score (VAS) of �30 mm,were on stable analgesics at least one month prior to en-rollment, and were stratified by narcotic use. Memantinetreatment was initiated at 10 mg/day and titrated to 20or 40 mg/day. The primary outcome measure was theweek 8 nocturnal peak pain intensity score, rated byVAS. Secondary measures included categorical pain in-tensity, sleep interference, patient pain relief and globalassessments. Paired group comparisons revealed a signif-icant difference in mean nocturnal VAS score at week 8between the 40 mg/day memantine and placebo groups(p�0.018). Patients in the 40 mg/day memantine groupalso had significant improvement in nocturnal categori-cal pain intensity (p�0.018) and sleep interference rat-ings (p�0.037) compared to placebo at week 8. Con-comitant narcotic use did not differentially influence theefficacy of memantine. Adverse events in memantine-treated patients were generally mild, and only dizzinessand nausea occurred more frequently compared withplacebo. Discontinuation rates due to adverse events weresimilar across the treatment groups. In conclusion, 40mg/day memantine was effective and well tolerated forthe treatment of diabetic PPN.

Research

MYOBLOC IN THE TREATMENT OF PIRIFORMIS SYNDROME—A DOSE-FINDING STUDY

Loren M. Fishman, M.D, Manhattan Physical Medicine and RehabilitationPiriformis syndrome (PS) occurs when the piriformismuscle compresses the sciatic nerve as it leaves the but-tock just below the greater sciatic foramen. Clinical signsfor PS include positive straight leg raise, weakened ab-duction of the flexed thigh, and tenderness at the inter-section of the muscle and nerve. Electrophysiological di-agnosis is made by comparing posterior tibial andperoneal H-reflexes elicited in the anatomical positionwith those obtained in flexion adduction and internal ro-tation (FAIR-test). Mean prolongation seen in normals is.01 milliseconds, (standard deviation � .62 millisec-onds). Taking three standard deviation prolongation ofthe H-reflex as the electrophysiological criterion for di-agnosis, along with two of the three clinical conditionscited above, four groups of five patients with piriformissyndrome were identified. Each patient agreed to anIRB-approved protocol in which initially five patients

Abstracts 183

were injected with 5000 units of Myobloc in four sepa-rate locations of the affected piriformis muscle underEMG guidance. Adverse effects and FAIR-tests werestudied at weeks 0, 2, 4, 8, and 12. Patients receivedphysical therapy twice weekly during that period. Afterone month surveillance, the second, third and fourthgroup were injected with 7500, 10,000 and 12,500 unitsof Myobloc in successive months. Side effect profile fordry mouth showed the most significant increase, from1.2 to 2.4 units of severity as dosage rose from 10,000units to 12,500 units of Myobloc. Patients’ visual ana-logue scale estimates of pain fell from an average of 6.7to 2.3 over the period, with H-reflex response in theFAIR-test showing parallel decline. These responseswere more dramatic at higher doses of Myobloc. Thisstudy suggests that physical therapy and 10,000 units ofMyobloc are a safe and effective treatment for PS, andsecondarily that the FAIR-test is an effective means ofdiagnosing PS and assessing its clinical improvement.

Research (Clinical)

OPIOID CONTRACTS AND PRIMARY CARE PHYSICIANS

Gagan Mahajan, MD1, Barth Wilsey, MD1,2, Sun Wong Jung, MD1,3 and Scott M. Fishman, MD1

1Division of Pain Medicine, University of California, Davis 2Northern CaliforniaVeterans Administration Pain Clinics 3Keimyung University, Taegu, Korea.Summary: The PCP was asked to collaborate with thepain specialist’s decision to use opioids by cosigning anopioid contract, with the understanding the PCP wouldassume the refills once the opioid regimen had becomestabilized. Preliminary analysis of the results stronglysuggests the opioid contract may be an effective way tonetwork specialty and primary care services in the deliv-ery of chronic opioid therapy.Methods: We conducted a retrospective chart review of 81patients with chronic non-malignant pain who were seen atour university Pain Clinic from November 1999–Septem-ber 2000. We asked those who signed the contract to de-liver it to their PCP for review. In cases where the patientdid not return the contract from the PCP, determining thereason(s) for this was attempted through a standardizedquestionnaire administered to the PCP via telephone.Results: Sixty-nine of the 81 patients (85%) signed thecontract. Forty-five (56% of the 81 enrolled patients;65% of the 69 signed contracts) were returned with thePCP’s signature. None of the 45 patients with a com-pleted contract encountered any difficulty in obtainingopioids upon discharge from the Pain Clinic. For the re-maining 24 (35%) incomplete contracts, we were able to

only contact 20 of the PCPs: 5 PCPs acknowledged re-ceiving the contract, and 15 did not. Among the latter,all claimed they would have signed the contract had theyreceived one.Discussion: Preliminary findings indicate many PCPs arewilling to collaborate with pain specialists in prescribingopioids long-term. A significant part of the failure in con-tracting resided with the patient. Reasons for unreturnedcontracts varied from patients not delivering it to theirPCP, to patients or PCPs misunderstanding what to dowith the contract after signing it. These data support theinclusion of the PCP in the contracting process as a prac-tical and accepted management strategy, particularly dur-ing and after the transition from specialty to primary care.

Research (clinical)

PAIN REDUCTION WITH OPIOID ELIMINATION

Edward Covington, MD, Cleveland Clinic Foundation; Margaret Kotz, DO, Cleveland Clinic FoundationThe last decade has seen a reversal of the historical beliefthat chronic opioid therapy (COT) was inadvisable in non-malignant palm. Numerous studies demonstrate sustainedpain reduction with chronic opioid therapy; however, thereare clinical reports and animal models that suggest chronicopioids may at times exacerbate pain. Clearly, many pa-tients without apparent structural deficit have persistentpain and dysfunction despite high dose opioid therapy.Thus, while opioids have been shown to be safe in longterm use, the question of efficacy remains. Predictors ofsuccess in COT are not fully established. Studies of in-trathecal opioids suggest that high levels of patient satis-faction and retrospective reports of benefit may occurdespite minimal change in pain level and function. Thisraises the question of whether at times the purportedbenefits of long-term opioid therapy may be illusory.Consecutive admissions to a chronic pain rehabilitationprogram (n � 228) were studied. This program representsa biased population in that many referrals have dysfunc-tion that is discordant with pathology, inordinate suffer-ing and dysphoria, poorly explained pain, or substance useproblems. Of 228, 56 were taking � 100 mg p.o. mor-phine equivalents/d on admission (mean 456 mg/d). Dataare available on 46 of these receiving ‘high dose’ opioids.Patients participated in a rehabilitation program that in-cluded reconditioning, cognitive behavioral psychother-apy, adjuvant medications, and elimination of opioidsand benzodiazepines.43 (93%) experienced a reduction in pain with opioidelimination (from 7.2 to 4.0/10). Three experienced anincrease in pain. Depression and functional impairmentalso improved.Cases will be presented of patients who believed they

184 Abstracts

were benefiting from chronic opioid therapy, but im-proved after opioid elimination. They commonly described“getting myself back” after elimination of opioids. Physi-ological considerations and treatment implications willbe described.

Research

PHYSIOLOGIC ABNORMALITIES AS BIOLOGIC MARKERS IN SEVERE, INTRACTABLE PAIN

Forest Tennant, MD, Dr PH; Laura Herman RNBSN FNP

Veract Intractable Pain Centers, 338 S. Glendora Ave., West Covina, CA 91790It is recognized that biologic markers of severe, intracta-ble pain (SIP) can help distinguish degrees of pain andassist in monitoring treatment effectiveness. Fifty (50.0%)adult ambulatory SIP patients, at the time of referral de-scribed their pain as constant, excruciating, produced abed or house-bound state, and was uncontrolled by non-opioid medications and low dosages of the weak opioids,hydrocodone or codeine. Patients were treated with along-acting opioid preparation consisting of methadone,oxycodone, morphine, or transdermal fentanyl in addi-tion to a short-acting opioid for breakthrough pain.These patients were screened before treatment and afterthree months of opioid treatment by: (1) blood pressure;(2) pulse rate; (3) morning cortisol and pregnenolone se-rum concentrations; and (4) erythrocyte sedimentationrate (ESR). The percentage of patients with physiologicabnormalities before and after three months of treat-ment were as follows: (1) hypertension above 140/90mm/Hg; 28 (56.0%) vrs 14 (28.0%); (2) tachycardiaabove 84/minute; 21 (42.0%) vrs 9 (18.0%); (3) elevatedserum cortisol concentration; 12 (24.0%) vrs 2 (4.0%);(4) low serum cortisol serum concentration; 7 (14.0% vrs1 (2.0%); (5) low pregnenolone serum concentration; 18(36.0%) vrs 3 (6.0%); and (6) elevated ESR; 10 (20.0%)vrs 3 (6.0%) (p�.05). Mean blood pressure, pulse rate,ESR, and serum concentrations of cortisol and preg-nenolone in patients who demonstrated a physiologicabnormality all positively and significantly (p�.05) al-tered these markers toward normal. This study indicatesthat some physiologic abnormalities, particularly thoserelated to pituitary-adrenal over-stimulation with excessoutput of catecholamines and glucocorticoids, may serveas biologic markers which can help to identify SIP andmonitor treatment effectiveness.

Clinical Research

PREDICTORS OF 6-MONTH POST-TREATMENT CHANGES IN PAIN, DEPRESSION AND ACTIVITY

LEVEL FOLLOWING A MULTIDISCIPLINARY PAIN TREATMENT PROGRAM

Lisa M. Benrud-Larson, Barbara K. Bruce, Christopher D. Sletten, John E. Hodgson, and Jeffrey D. Rome, Mayo Clinic and Foundation, Rochester, MNDespite much evidence regarding the effectiveness ofmultidisciplinary pain treatment programs, limited dataexist on factors that predict relapse. The present studyinvestigated factors associated with 6-month follow-upchanges in pain severity, depression, and activity levelamong patients enrolled in a chronic pain rehabilitationprogram. Patients (N�101) with heterogeneous painconditions who entered the program between 1998 and2000 completed measures of pain severity, depression,activity level, physical function, and catastrophizing atadmission, discharge, and 6-month follow-up. Paired t-tests revealed significant pre-post treatment improve-ment in all variables. Mean scores on pain severity andcatastrophizing continued to improve from discharge tofollow-up, while treatment gains in depression and gen-eral activity remained stable and physical function de-creased. Hierarchical regression analyses revealed thatdischarge pain severity and catastrophizing indepen-dently predicted follow-up changes in depression aftercontrolling for discharge levels of depression (R2 �

26.5%; p � .001). Patients reporting greater pain sever-ity and catastrophizing at discharge were more likely toreport an increase in depression at 6 months post-treat-ment. Similarly, discharge pain severity and catastroph-izing independently predicted follow-up changes in gen-eral activity (R2 � 8%; p � .001) after controlling fordischarge activity level. Patients reporting greater painseverity and catastrophizing at discharge were morelikely to report a decrease in activity level at follow-up.Discharge physical function was the only independentpredictor of follow-up changes in pain severity after con-trolling for discharge pain severity (R2 � 10%; p �

.001). Patients reporting poorer physical function at dis-charge were more likely to report an increase in pain se-verity at follow-up. These results point to factors thatmay be important in predicting relapse following treat-ment for chronic pain. In addition to elevated pain sever-ity and low activity level, patients who are dischargedwith high levels of catastrophizing may be at heightenedrisk of relapse.

Research (Clinical)

PRE-OPERATIVE PAIN EDUCATION: CHILDREN AND PARENTS’ PERSPECTIVES

Margie Quinn-Crandall and Cathy R. Lammers, Department of Anesthesiology and Pain Medicine, University of California, Davis

Abstracts 185

Although proactive pain education and preparation forparents and children is mandated by regulatory agencies,little is known about what children and parents perceive asimportant for caregivers to learn about pain. The paucityof research on the effects that a proactive pain educationand preparation may have on the pain experience andmanagement of children’s pain provides little substantiveknowledge to guide the practice of nurses and physicians.An exploratory qualitative study was designed to explorewhat children and their parents perceive to be the mostimportant features of their pain prior to surgical proce-dures. A sample of twelve children (7 to 13 years) who hadexperienced a tonsillectomy and adenoidectomy were in-terviewed with their parents in the clinic setting. All par-ents and children described a need for preoperative paineducation. The majority of parents and children describeda need for specific pain education including location andduration of pain, specific pharmacological and nonphar-macological therapies, and preoperative introduction ofpain intensity scales. Children described concern abouteducation regarding the expected intensity of pain, angerwhen realistic pain education was withheld, and the needfor pain scales in the home. Although this research sup-ports previous studies that parents and children view paineducation as important and want a collaborative role intheir pain management (1,2,3), these findings offer spe-cific insights into what parents and children perceive asimportant components of pain education. Based on studyfindings, educational materials were developed and futureresearch will investigate the influence that proactive paineducation has on clinical pain outcomes.

1 Palmero T and Lambert S. A descriptive study of chil-dren’s beliefs concerning the use of analgesics in treat-ing postoperative pain. Children’s Health Care, 1997;26:1:47–59.

2 Bennett-Branson S and Craig K. Postoperative pain inchildren: Developmental and family influences onspontaneous coping strategies. Canadian Journal ofBehavioral Science, 1993; 25:3:355–383.

3 Alex M and Richie J. School-aged children’s interpre-tation of their experience with acute surgical pain.Journal of Pediatric Nursing, 1992; 7:3:171–180.

RETROSPECTIVE ASSESSMENT OF FREQUENCY OF DOSING OF SUSTAINED RELEASE OPIATE PREPARATIONS IN CHRONIC PAIN PATIENTS

D. Adams, I. Gunyea, B. Bhakta, V. Movva, S. Ward, M. Jenson, M. Royal

Pain Evaluation and Treatment Center, Tulsa, OKDepartments of Internal Medicine and Anesthesiology/Pain Management, Oklahoma University College of Medicine (Tulsa and Oklahoma City)A retrospective chart review of 258 patients (67 on Du-ragesic®/fentanyl patches, 58 on MS Contin®/sustainedrelease morphine, 57 on Kadian®/sustained release mor-

phine, and 76 on Oxycontin®/sustained release oxy-codone) was performed to evaluate the dosing frequencyof various sustained release (SR) opiate preparations inpatients with primarily chronic benign pain. Pain diag-noses included chronic degenerative conditions, arthrid-ities, fibromyalgia, spine-related conditions, abdomino-pelvic pain, complex regional pain syndromes, peripheralneuropathies, postherpetic neuralgia, radiculopathies, mul-tiple sclerosis, and HIV neuropathy. There was no sig-nificant difference in the distribution of pain syndromesin each group or in the age and sex distribution. Durage-sic® (25–500 mcg/h) was dosed q 72 h in 76.1% of pa-tients (51/67) and q 48 h in 23.9% (16/67). Breakthrough(BT) medication (immediate release opiate formulation)was used in 58.2% (39/67). MS Contin® (15–800mg/d)was dosed q.d., b.i.d., t.i.d. or q.i.d. in 1.7 (1/58), 27.6(16/58), 67.2 (39/58), and 3.4% (2/58) of patients, respec-tively. Dosing more frequently than b.i.d. was seen in70.6% and additional BT medication was required in56.9% (33/58). Kadian® (20–400mg/d) was dosed q.d.,b.i.d., t.i.d. or q.i.d. in 61.4 (35/57), 33.3 (19/57), 3.5 (2/57),and 1.8% (1/57) of patients. Dosing more frequentlythan b.i.d. was seen only in 5.3% and BT medication wasused in 42.1%. Oxycontin® (20mg-320mg/d) was dosedb.i.d., t.i.d., or q.i.d. in 13.2 (10/76), 59.2 (45/76) or 27.6%(21/76) of patients. Dosing more frequently than b.i.d.was seen in 86.8% and BT medication was required in56.6% (43/76). While there are many reasons for morefrequent dosing of SR opiates, nearly every patient inthis analysis reported perceived end-of-dose failure ofanalgesia as the reason for taking the medication morefrequently. Kadian® appeared to maintain a less frequentdosing schedule than other SR opiate preparations.

Research Clinical

ROFECOXIB COMPARED TO OXYCODONE/ACETAMINOPHEN FOR POSTOPERATIVEDENTAL PAIN

James Fricke, DDS, MSD, PPD Development, Theodore Vassil, MS, Merck Research Laboratories, Paul Kotey, PhD, Merck Research Laboratories, Scott Korn, MD, Merck Research LaboratoriesBackground: Rofecoxib (ROF) is a selective cyclooxyge-nase-2(COX-2) inhibitor approved for the treatment ofacute pain and primary dysmenorrhea as well as osteoar-thritis. Aim: This single dose, double-blind, randomizedplacebo-controlled trial was undertaken to compare theanalgesic efficacy of ROF 50 mg (n�90), Oxycodone/Acetaminophen 5/325 mg (Oxy/APAP) (n�91) and pla-cebo (PBO) (n�31). Methods: Patients with moderateto severe pain following extraction of at least 2 third mo-lars (at least one bony impaction) were randomized tostudy medication, rated pain intensity and pain relief at

186 Abstracts

prescribed times over 24 hours, and recorded time to per-ceptible pain relief and time to meaningful pain relief bystopwatch. Primary comparisons were response to therapyover the first 6 hour time period based on recommendeddosing for Oxy/APAP. Results: Both ROF and Oxy/APAP were significantly greater than PBO in all measuresof onset, peak, duration, and overall analgesic effect, in-cluding TOPAR6 (Total Pain Relief Score over 6 hours)and global response to therapy at 6 hours. ROF dem-onstrated significantly greater efficacy than Oxy/APAPon all measures of overall analgesic effect, includingTOPAR6, TOPAR4 and global response to therapy at 6and 24 hours. Compared to Oxy/APAP, ROF had signifi-cantly greater overall and peak analgesic effect, signifi-cantly longer duration of analgesic effect, and similar timeto onset of analgesic effect. ROF and PBO had generallysimilar adverse experience profiles; compared to Oxy/APAP, ROF patients had significantly fewer episodes ofnausea (19% vs 40%) and vomiting (7% vs 23%). Con-clusion: Rofecoxib 50 mg was more effective than Oxyco-done/Acetaminophen 5/325 mg for relief of dental pain.

Clinical Research

SAFETY PROFILE AND ECONOMICS WITH THE USE OF FENTAYL AND HYDROMORPHONE AS POSTOPERATIVE EPIDURAL ANALGESICS

Senthilkumar Sadhasivam, Balachundhar Subramaniam, Vimal Akhouri, Carolyn Debeauport, Thomas Simopoulos, Christine Peeters-Asdourian, Robert I. Cohen. Arnold Pain Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MAA nation-wide shortage of fentanyl increased the use ofepidural hydromorphone for postoperative analgesia inour hospital. Compared to fentanyl, the more hydro-philic hydromorphone is expected to spread cephalad inCSF and achieve widespread analgesia with an increasedrisk of respiratory depression. We aimed to evaluate thesafety, side effect profile and costs to manage postopera-tive pain and associated side effects with epidural fenta-nyl and hydromorphone. With institutional approval,1002 adult surgical in-patients who required postopera-tive epidural analgesia were studied retrospectively basedon postoperative pain consultation and daily pain teamfollow-up reports, and chart review. The demographicdata and the distribution of catheter placements at upperand lower thoracic and at lumbar levels were compara-ble. 525 patients received epidural fentanyl 4�g/cc with0.1% bupivacaine (F-group) and 477 patients receivedepidural hydromorphone 20�g/cc with 0.1% bupiv-acaine (H-group). The epidural analgesic efficacy andthe number of effective epidural analgesic days werecomparable in both the groups. The incidences of side

effects including respiratory depression, drowsiness, hy-potension, nausea/vomiting, pruritus, confusion, motorweakness and ileus were comparable in the F- and theH-groups, but the cumulative incidence of all the side ef-fects was significantly less in the H-group (34%) thanthe F-group (42%, p�0.0016) (Table). Urinary reten-tion was not compared as �50% of patients had a uri-nary catheter as part of routine postoperative care. Thedirect cost of epidural analgesic solution, calculated bymultiplying mean epidural analgesic days, mean epiduralrate, and cost per unit of epidural analgesic solution was$23.4 in the F-group and $22.5 in the H-group. Epiduralhydromorphone has successfully taken over the place ofepidural fentanyl in the postoperative pain managementat our institution with comparable efficacy, safety andcosts for analgesia. With the fentanyl shortage over, hy-dromorphone has remained the preferred epidural anal-gesic as the patients in the H-group had less overall inci-dence of side effects and less severe nausea and vomiting(reflected by decreased antiemetic intervention). Thoughthe cost to treat PONV per patient was comparable(F-group $4.3 vs. H-group $4.8), less frequent need forantiemetics in the H-group has a cost saving potential.

Research

SELF-TREATMENT WITH ORAL TRANSMUCOSAL FENTANYL CITRATE TO PREVENT EMERGENCY ROOM VISITS

Forest Tennant, MD DR PH; Laura Herman, RN, BSN, FNP; Veract Intractable Pain Centers, West Covina, CA

Table Epidural opioid associated side effects

Associated Effect FentanylHydro-morphone P-Value

Total side effects (%) 219 (41.7) 162 (33.9) 0.01*Respiratory depression (%) 9 (1.7) 10 (2.1) 0.66Drowsiness (%) 40 (7.6) 48 (10.1) 0.19Hypotension (%) 52 (9.9) 36 (7.6) 0.18Pruritus (%) 57 (10.9) 62 (12.9) 0.33Nausea/Vomiting (%) 81 (15.4) 56 (11.7) 0.08Ileus (%) 6 (1.1) 3 (0.6) 0.38Motor weakness (%) 22 (4.2) 12 (2.5) 0.14Confusion (%) 9 (1.7) 6 (1.3) 0.55Dizziness (%) 7 (1.3) 4 (0.8) 0.20Inflamed site (%) 6 (1.1) 2 (0.4) 0.35Spinal migration (%) 1 (0.2) 2 (0.4) 0.93Catheter shear (%) 2 (0.4) 0 (0) 0.69Cardiac event (%) 6 (1.1) 1 (0.2) 0.16Respiratory distress/OSA (%) 2 (0.4) 1 (0.2) �0.99SE of treatment for NV (%) 0 (0) 2 (0.4) 0.55Side effects requiring treatment

Respiratory depression (%) 9 (1.71) 10 (2.1) 0.66Hypotension (%) 28 (5.3) 21 (4.4) 0.50Pruritus (%) 21 (4.0) 18 (3.8) 0.85Nausea/Vomiting (%) 38 (7.2) 18 (3.8) 0.02 *

* Statistically significant for p�0.05

Abstracts 187

Emergency room visits by chronic pain patients who ex-perience episodic pain flares are an expensive, time-con-suming public health problem. Available opioid agentsfor at-home, patient self-treatment consist of short-act-ing oral, suppository, or injectable compounds whichhave delayed, inconsistent, or unpredictable analgesic ef-fects. Oral transmucosal fentanyl citrate (OTFC) is anew potent, opioid preparation used by buccal or sub-lingual routes, and it produces potent analgesic effectsequal to intravenous morphine within 5 to 10 minutes.To determine if OTFC is effective and safe for at-hometreatment of emergency pain flares, 90 chronic pain pa-tients with a variety of painful conditions were treatedwith a long-acting opioid consisting of transdermal fen-tanyl, methadone, or a sustained release oxycodone ormorphine preparation. All additionally used a short-act-ing oral, suppository, or injectable opioid for self-treat-ment of emergency flares. All were given OTFC to al-ternatively substitute for their current opioid to self-treatemergency flares. Patients were surveyed after three ormore months of OTFC use, and 86 (95.6%) believedthey could safely and effectively treat their emergencypain flares with OTFC. Seventy-one (78.8%) believedOTFC had prevented the necessity to attend an emer-gency room or enter a hospital for pain control. Forty-five (50.0%) patients had collectively used OTFC for375 months and during this period could specifically es-timate, based on their previous experience, they hadavoided 474 emergency room and 220 hospital admis-sions. This translates to 1.26 emergency room and 0.6in-patient admissions per month per patient. There wereno emergency visits in the entire group during the studyperiod, and 76 (84.4%) preferred OTFC over their cur-rent emergency opioid. OTFC warrants further studyfor self-treatment of emergency flares to improve patientcare and reduce costs.

Clinical Research

THE CORRELATION BETWEEN THE FIBROMYALGIA IMPACT QUESTIONNAIRE AND THE HEALTH STATUS QUESTIONNAIRE: IMPLICATIONS FOR USE IN PAIN STUDIES

In recent years, there has been increased attention toquantifying psychosocial variables associated with fibro-myalgia and other pain populations. It is widely recog-nized that patient perception of functioning has a greatinfluence on overall adaptation to chronic pain and mo-tivation for rehabilitation. Two psychometric scales havebeen used for this purpose, the Fibromyalgia ImpactQuestionnaire (FIQ) and the Health Status Question-naire (HSQ). The FIQ was developed as a specific mea-sure of the impact of fibromyalgia has across several do-

mains. These include specific physical symptoms, physicalfunctioning, ability to work and perform activities ofdaily living, and emotional functioning. The FIQ hasgood psychometric properties and has been well vali-dated in a number of studies. By its nature however, itsuse is confined to this specific pain population. TheHSQ has been designed to be a measure of perceivedhealth and functioning in a more general medical popu-lation. In our experience with both of these measures itseemed that there would be significant overlap in themeasured constructs. This study compared the subscalesof the FIQ with the Physical Functioning Subscale andthe Mental Health Subscale from the HSQ. All compar-isons using a Pearson Correlation were significant at p �0.001. These results indicate a high degree of overlapbetween these two measures. This overlap further con-firms the construct validity of the FIQ. Further, sincethese two measures appear closely related, the use of theHSQ in other pain populations could be considered avalid measure of functioning and perceived health status.Both of these measures have adequate reliability andshow changes when used as treatment outcome variables.

Research

A DESCRIPTIVE ANALYSIS OF LONG-ACTING OPIOID USE IN END-STAGE CANCER PATIENTS: CORRELATION OF AGE, GENDER, AND PRIMARY SITE WITH DOSE

Susannah Hall, ExcelleRx, Inc, Rollin M. Gallagher, MCP Hahnemann School of Medicine, Calvin Knowlton, ExcelleRx, Inc, and Douglas Weschules, ExcelleRx, Inc.Long-acting opioids are considered to be the corner-stone of cancer pain treatment, especially in the hospicepatient. Increasing age has been associated with de-creased opioid requirements in cancer and post-opera-tive patients, although published reports do not agreeabout the age at which this decreased requirement ap-pears. In terminal cancer patients, there are mixed re-ports as to whether an association between gender andopioid dose exists. Possibly the presence of relativelymore or less painful gender-specific cancers contributedto those differing results. Some studies suggest that cer-tain primary cancer sites require higher opioid dosesthan others, but few have controlled for age. The objec-tive of this retrospective analysis is to describe the corre-lation of age, gender, and primary cancer site with long-acting opioid doses prescribed for hospice patients at theend of life, defined as the last long-acting prescriptionwritten prior to death. All hospice patients admitted to aNorth American palliative care specialty pharmacy be-tween 4/1/00 and 3/31/01 with the primary diagnosis of

188 Abstracts

cancer and who were prescribed transdermal fentanyl,sustained release oral morphine, or sustained release ox-ycodone were included in this analysis. A total of 7201patients met the inclusion criteria. Age was a highly sig-nificant determinate of dose (p � 0.0001) with patientsprescribed increasingly lower long-acting opioid doseswith each decade of life. The final morphine equivalentdose of long-acting opioid prescribed prior to death was� 60 mg/day in 25.7% of patients 40–49 years, 29.1% ofpatients 50–59 years, increasing to 57.8% of patients80–89 years, and 69.6% of patients � 90 year. The sexeswere compared for lung, colorectal, and pancreatic can-cer separately and no significant difference between thesexes was found by Chi-square test, nor by logistic re-gression with age controlled. The correlation of the pri-mary site of cancer with the final prescribed long-actingopioid dose will be presented.

THE PHARMACOKINETICS (PK) AND SAFETY OF ORAL TRANSMUCOSAL FENTANYL CITRATE (OTFC®) ADMINISTERED TO HEALTHY VOLUNTEERS AS TWO 400 �g ACTIQ® DOSES OR AS A SINGLE 800 �g ACTIQ® DOSE

Talmage Egan, MD, Steven E. Kern, PhD, University of Utah, University Hospital, Salt Lake City, UT, Kiumars Q. Vadiei, PhD, RPh, FCP, Medical Affairs, Cephalon, Inc., West Chester, PABackground: Breakthrough pain (BTP) is a transientexacerbation of pain that occurs on top of a backgroundof stable but persistent pain. ACTIQ® (oral transmu-cosal fentanyl citrate; OTFC®) is a novel product de-signed to deliver rapid analgesia for the treatment ofBTP. ACTIQ is available in 6 dosage strengths (200–1600 �g) to allow individualization of dosing. The effec-tive dose is determined by titration and, an efficient ti-tration process can maximize patient satisfaction. Titra-tion could be expedited and made more efficient bysimultaneously dosing with two units instead of a singleequivalent higher dosage unit. This study evaluated thePK and safety of simultaneous administration of twoACTIQ 400 �g doses compared with a single 800 �gdose.Methods: An open-label, randomized, 2-period, cross-over study was conducted in 12 healthy opioid-naïve vol-unteers. Treatments, separated by a 1-week washout pe-riod, were: two simultaneous ACTIQ 400 �g doses and asingle 800 �g dose. Venous fentanyl blood concentra-tions (serum) were assayed by validated LC/MS/MS.Results: The disposition of fentanyl did not differ be-tween treatments, as supported by the following PK pa-rameters for the 2�400 �g and 1�800 �g ACTIQdoses, respectively: mean (� sem) Cmax (ng/mL) 1.090 (�0.228) vs. 1.097 (� 0.508); median Tmax (hr) 0.582 vs.

0.510; and AUC0–24h (ng�hr/mL) 6.911 (� 2.558) vs.6.123 (� 2.452). The incidence of the most common ad-verse events (asthenia, vasodilatation, headache, nausea,and somnolence) was similar between treatments. No se-rious AEs were reported.Conclusion: The PK and safety of ACTIQ adminis-tered as two simultaneous 400 �g doses are comparableto a single 800 �g dose. These results support expeditingtitration of ACTIQ by allowing patients to use two dosessimultaneously to match the effect derived from anequivalent single higher dose. This may allow morerapid and efficient management of BTP.

Support: This study was supported by Cephalon, Inc.,West Chester, PA.

Clinical Cases

THE SUCCESSFUL APPLICATION OF MEDITATIVE PRINCIPLES TO TREATMENT REFRACTORYPAIN CONDITIONS

Daniel M. Rockers, Ph.D. University of California, Davis, Sacramento, CAThe potential psychological mechanisms mediating phys-ically expressed pain are investigated through separateyet related means in case studies. In case 1, pt BI sufferedfrom RSD/CRPS I and was treated with GSR and ther-mal, while in case 2 TT experienced a number of diffi-cult conditions including biofeedback sciatica, acid reflux,breast soreness, anxiety and headaches and was treatedwith hypnotically induced meditation and self-inducedmeditation. At three months into treatment, BI had re-duced pain ratings by 40%, increased sleep time by afactor of two. At four months into treatment, TT haddecreased pain ratings by 40% and decreased pain medi-cations intake by 50%.Although the treatment modalities themselves appeardisparate, they both involve the common underlyingtheme of regulating attentional thought processes froman intentional and conscious perspective. As applied topain states this is useful because each thought, feeling,idea or perception involves some type of physical orphysiological response. Uncontrolled and unregulatedthought process of the mind can create (and through ha-bituation maintain) offensive physiological conditions.Extant examples include angina, hypertension, and ten-sion headache. Specific methodology applied to theabove cases involved training in elements of Hinduist1,Buddhist2 and Taoist3 meditative principles with the goalbeing the increase in and volitional directing of atten-tion. This involved quieting the thought processes of themind and was accomplished in a variety of ways, includ-ing the utilization of external devices such as biofeedback

Abstracts 189

instruments, through breathing exercises4, and examina-tion of thought processes.1 Easwaran, Eknath. (1987). The Upanishads. Tomales,California: Nilgiri Press1 Easwaran, Eknath. (1985). The Dhammapada. Tomales,California: Nilgiri Press1 Evans-Wentz, W.Y. (2000). The Tibetan Book of theGreat Liberation: The method of knowing nirvana throughknowing the mind. New York: Oxford University Press.1 Lamrimpa, G. (1995). Calming the Mind: Tibetan Bud-dhist Teachings on Cultivating Meditative Quiescence. Ith-aca, NY: Snow Lion Press1 Walker, B. (1992). Hua Hu Ching: The Teachings of LaoTzu. Clark City Press.1 Rama, S., Ballentine, R., & Hymes, A. (1998). The Sci-ence of Breath.

Experimental Research

TOXICITY AND EFFICACY OF INTRATHECAL MIDAZOLAM

Mary J. Johansen, William C. Satterfield, Walter B. Baze, Tamara Lee Gradert, Samuel J. Hassenbusch, The University of Texas M. D. Anderson Cancer CenterMidazolam (MDZ) administration by continuous in-traspinal (IS) infusion is an effective treatment strategyfor chronic pain. While intrathecal MDZ doses of 0.3––12 mg/day administered alone or in combination withother agents (morphine, clonidine, and bupivacaine)have been well tolerated in humans, neurotoxicity hasbeen reported in rats and rabbits administered species-equivalent doses within this range. To further investi-gate the toxicity and efficacy of a preservative-free in-trathecal MDZ HCl preparation, we conducted a studyin sheep and pigs delivering MDZ using implanted infu-sion systems (pumps plus silicone catheters). Thesepumps delivered preservative-free 0.9% saline for 5–7days prior to treatment. Sheep were randomized to re-ceive MDZ 5 mg/day (n�4) or 15 mg/day (n�7) � 43days, or saline control (n�2) � 43 days. Behavior andneurological function were documented daily and anal-gesia was evaluated by response to an acute pain stimulusproduced by a mechanical device attached to the foreleg.Pigs were evaluated for toxicity only and were adminis-tered doses of 5 (n�1) or 15 (n�1) mg/day, or salinecontrol (n�1). Histological evaluations of spinal cordtissue, and CSF chemistry and cytology were performedon all animals. No clinical signs of toxicity were observedin any animal. In sheep, MDZ doses of 5 and 15 mg/dayincreased pain tolerance 75% and 45%, respectively,versus control. Gross and microscopic evaluation of spi-nal tissue revealed mild inflammation surrounding the

catheter tract in all animals in both treated and controlgroups. This inflammation was likely attributable to themechanical presence of the catheter. Elevation of CSFtotal protein was observed in one animal administered 5mg/day. Overall, these data demonstrate that continuouslong-term IS infusion of preservative-free MDZ at dosesof 5–15 mg/day is both efficacious and well tolerated.(Sponsored by M. D. Anderson Cancer Center andMedtronic, Inc.)

Clinical

TREATMENT WITH BOTULINUM TOXIN TYPE B (MYOBLOC) INJECTIONS IN THREE PATIENTS WITH MYOFASCIAL PAIN

Srinivas Nalamachu, MDMid-America Physiatrists PAOverland Park, KSBotulinum toxin type B (BoNT-B; Myobloc) is an anti-genically distinct botulinum toxin serotype that is effec-tive for managing patients with cervical dystonia. Studiesshow that BoNT-B significantly reduces the pain associ-ated with this disorder. The mechanism by which it pro-vides pain relief may be related to chemodenervation aswell as other potential theoretical mechanisms. We re-port the results of three patients (2 female; 1 male) withmyofascial pain who were treated with BoNT-B injec-tions. Patients were between 30–40 years of age and havefailed treatment with oral anti-inflammatories and mus-cle relaxants, and have not had good results with physicaltherapy or conventional modalities, such as ultrasoundand TENS. Pain was measured on a VAS scale pre- andpost- injection. Patients were injected with a 5000-Udose of BoNT-B into an average of 5 muscles with anequal dose of 1000 U into each injection site. Muscles in-jected include cervical paraspinals, trapezii, supraspina-tus, and infrapsinatus. Prior to injection, patients were 8/10, 8/10, and 10/10 in pain severity. Results of treatmentwith BoNT-B in our three patients with myofascial painwere very good. At the 1-week and 1-month follow-up,patients reported significant improvements in pain se-verity: 2/10, 2/10, and 3/10, respectively. They also re-ported a decreased need in the medications that theywere taking for pain control. One patient has returnedfor re-injection and to date has received a total of 2 in-jections, supporting a positive and continuous responseto treatment. Overall, BoNT-B was very well-tolerated.One patient reported flu-like symptoms 12 hours afterthe first injection that lasted for 24 hours, but this eventdid not recur with further injections. The two other pa-tients have reported no side effects. Based on our find-ings, further studies of BoNT-B in the treatment of my-ofascial pain are warranted.

190 Abstracts

Clinical

UNINTENTIONAL OVERDOSE WITH INTRATHECAL ZICONOTIDE

Steven G. Charapata MD, Research Medical Center, Kansas City, MO; David Ellis MD, PhD, Elan Pharmaceuticals, South San Francisco, CAZiconotide is a novel, N-type, voltage-sensitive calciumchannel (VSCC) blocker, with well-documented efficacyas an intrathecal (IT) analgesic. Ziconotide has been ad-ministered to over 1000 chronic pain patients in nineclinical trials. Over 350 patients have been on ziconotideIT therapy for more than three months in a long-termsafety and tolerability study. Common adverse events forziconotide include dizziness, nausea, nystagmus, abnor-mal gait, constipation, urinary retention, somnolence,postural hypotension, vomiting, confusion and abnormalvision. Ziconotide adverse events are recognizable, re-versible and manageable, by dose adjustment and slowdose titration. Case reports of unintentional overdose insix chronic pain patients treated with IT ziconotide arepresented. These unintentional overdoses were attribut-

able to pump programming or dilution errors; none werelethal. The patient who received the highest overdosewas administered 31 mcg/hr over 24 hours, or nearly 750mcg ziconotide, total. This hourly dose rate is 300-foldthe current recommended initial dose rate of 0.1 mcg/hr.This patient was sedated, but arousable; vital signs werestable and patient had no change in blood pressure. Hissymptoms resolved within 24 hours. His Visual AnalogScore of Pain Intensity (VASPI) was reduced from 82 atbaseline to 2.5 at the end of the titration period. The pa-tient elected to continue in the long-term IT ziconotidestudy. The other 5 cases of inadvertent overdose wereless severe, with dose rate at 5 mcg/hr or less. Associatedadverse events also resolved within 24-hours of discon-tinuing ziconotide infusion. Unlike an unintentionaloverdose with IT morphine, which slows respiration andcould potentially lead to hypoxia, coma or death; zi-conotide does not produce respiratory depression. Notolerance to the analgesic effect of ziconotide, or with-drawal symptoms after discontinuation of the drug havebeen reported. Ziconotide has a wide margin of safety asan IT analgesic.