K30 case study: innovative K30 case study: innovative treatment approach to treatment approach to myofascial neck painmyofascial neck pain

Marc Brodsky, MDMarc Brodsky, MD

UCLA Center for East-West MedicineUCLA Center for East-West Medicine

May 27, 2008May 27, 2008

Patient presentationPatient presentation

24 yo female medical 24 yo female medical student with a one-student with a one-year h/o neck pain that year h/o neck pain that began during a time of began during a time of intense stress during a intense stress during a visit with her parentsvisit with her parents

DyspepsiaDyspepsia Constipation Constipation DysmenorrheaDysmenorrhea Dry, red eyesDry, red eyes Cold intoleranceCold intolerance InsomniaInsomnia

Mechanistic (parts, Mechanistic (parts, objects, contents)objects, contents)

Problems in Problems in isolationisolation

Analytical thinkingAnalytical thinking

Treatment aims to Treatment aims to block, stimulate, or block, stimulate, or replacereplace

Holistic (whole, Holistic (whole, relationships, relationships, patterns)patterns)

Problems of the Problems of the systemsystem

Principles of Principles of organizationorganization

Treatment Treatment emphasizes self-emphasizes self-healing healing

How is CAM classified?How is CAM classified?

ttp://nccam.nhih.gov/

Integrative MedicineIntegrative Medicine

Healing oriented medicine that takes account of the whole Healing oriented medicine that takes account of the whole person (body, mind and spirit) including all aspects of lifestyle. It person (body, mind and spirit) including all aspects of lifestyle. It emphasizes the therapeutic relationship and makes use of all emphasizes the therapeutic relationship and makes use of all appropriate therapies, both conventional and alternative.appropriate therapies, both conventional and alternative.

Curriculum in Integrative Medicine: A Guide for Medical EducatorsCurriculum in Integrative Medicine: A Guide for Medical Educators. 2003, Consortium of Academic Health . 2003, Consortium of Academic Health Centers for Integrative MedicineCenters for Integrative Medicine

Hands-on physical examHands-on physical exam

Locally tender point Locally tender point in taut band of in taut band of musclemuscle

Characteristic Characteristic radiation of pain radiation of pain with pressurewith pressure

Pressure can Pressure can produce twitch produce twitch responseresponseTravell, J.G., and Simons, D.G., Myofascial pain and dysfunction: the trigger point manual. 1983: Baltimore.

Standard of care for myofascial painStandard of care for myofascial pain

Trigger point Trigger point injectioninjection

Physical therapyPhysical therapy Medications Medications

(muscle relaxant, (muscle relaxant, NSAID, botox)NSAID, botox)

Lifestyle changes to Lifestyle changes to address factors that address factors that contribute to trigger contribute to trigger pointspoints

http://www.emedicine.com/pmr/topic84.htmhttp://www.emedicine.com/pmr/topic84.htm

Wellness treatment Wellness treatment planplan

http://www.ehcca.com/presentations/hitsummit2/5_01_3.pdf

What is quality of lifeWhat is quality of life

The World Health The World Health Organization Organization defined "quality of defined "quality of life" in its life" in its constitution in constitution in 1948 to include 1948 to include physical, mental, physical, mental, and social well-and social well-being, and not just being, and not just the absence of the absence of disease or illness.disease or illness.

Physical Health

Physical function

(10)

Physical function

(10)

Role –physical

(4)

Role –physical

(4)Pain (2)Pain (2)

General Health

(5)

General Health

(5)

SF-36: Physical healthSF-36: Physical health

Mental Health

Emotional Well-

Being (5)

Emotional Well-

Being (5)

Role- emotional

(3)

Role- emotional

(3)

Energy/ fatigue (4)Energy/

fatigue (4)

Social function

(2)

Social function

(2)

SF-36: Mental healthSF-36: Mental health

Integrative approach Integrative approach to patients with neck to patients with neck painpain Pilot data from a Pilot data from a

cohort of 50 cohort of 50 consecutive patients consecutive patients with neck pain with neck pain recruited for 2000-recruited for 2000-2010 Neck Pain Task 2010 Neck Pain Task ForceForce

Compare change in Compare change in health-related quality health-related quality of life (HRQOL) at of life (HRQOL) at baseline and after 6 baseline and after 6 weeks of treatmentweeks of treatment

Change in SF-36 scoresChange in SF-36 scores

34

36

38

40

42

44

46

PF Role-P Pain Gen H Energy Social Role-E EWB

Baseline

Followup

Score

Multi-item scales

Statistical significanceStatistical significance

DeltaDelta t-testt-test prob.prob.

PF-10PF-10 2.62.6 2.212.21 .0334.0334

RP-4RP-4 3.43.4 2.802.80 .0081.0081

BP-2BP-2 2.82.8 3.093.09 .0038.0038

GH-5GH-5 1.91.9 2.282.28 .0287.0287

EN-4EN-4 3.33.3 2.762.76 .0090.0090

SF-2SF-2 2.32.3 1.541.54 .1324.1324

RE-3RE-3 1.51.5 0.820.82 .4152.4152

EWB-5EWB-5 2.72.7 2.032.03 .0500.0500

Research interest: is capsaicin Research interest: is capsaicin an effective biologic treatment an effective biologic treatment for myofascial pain?for myofascial pain? Capsaicin binds to a vanilloid Capsaicin binds to a vanilloid

type I receptor (VR1) on a type I receptor (VR1) on a trigeminal non-myelinated trigeminal non-myelinated group C fibergroup C fiber

Influx of sodium and calcium Influx of sodium and calcium ions results in depolarization, ions results in depolarization, which in turn opens voltage which in turn opens voltage gated sodium channels (VGSC) gated sodium channels (VGSC) and generates an action and generates an action potential along the nerve fiberpotential along the nerve fiber

Transmitter substances Transmitter substances including glutamate, including glutamate, Substance P (SP) und Substance P (SP) und Calcitonin Gene Related Calcitonin Gene Related Peptide (CGRP) transfers the Peptide (CGRP) transfers the signal to central neurons signal to central neurons responsible for the perception responsible for the perception of irritation and painof irritation and pain

Topical capsaicin and Topical capsaicin and analgesiaanalgesia

Diabetic and post-Diabetic and post-herpetic neuropathyherpetic neuropathy

OsteoarthritisOsteoarthritis Rheumatoid arthritisRheumatoid arthritis Post-mastectomy Post-mastectomy

pain pain

(Whittaker AL, Kennedy DT, Small (Whittaker AL, Kennedy DT, Small RE. Adjuvant agents for managing RE. Adjuvant agents for managing chronic pain. chronic pain. APS Bulletin.APS Bulletin. 1999:9) 1999:9)

What is a hydrogelWhat is a hydrogel

Polymer chains Polymer chains that are water-that are water-insolubleinsoluble

Can contain over Can contain over 99% water99% water

Natural or Natural or synthetic synthetic polymerspolymers

Capsaicin-containing Capsaicin-containing hydrogelhydrogel

Improve the Improve the permeability and permeability and patient compliance patient compliance of existing cream of existing cream dosage formsdosage forms

Hydrogels have Hydrogels have been investigated been investigated because of their because of their controlled-release controlled-release characterization and characterization and good tissue good tissue compatibilitycompatibility

Journal articleJournal article

Wang Y, Hong C, Chiu W, Fang Wang Y, Hong C, Chiu W, Fang J. In vitro and in vivo J. In vitro and in vivo evaluations of topically applied evaluations of topically applied capsaicin and nonivamide from capsaicin and nonivamide from hydrogels. International hydrogels. International Journal of Pharmaceutics 234 Journal of Pharmaceutics 234 (2001) 89-104.(2001) 89-104.

FDA guidelines to evaluate FDA guidelines to evaluate in vitro and in vivo in vitro and in vivo absorptionabsorption Permeation of Permeation of

stratum corneum stratum corneum (SC) is rate (SC) is rate limiting steplimiting step

Membrane to Membrane to assess in vitro assess in vitro release of drugrelease of drug

Dermato-Dermato-pharmacokinetics pharmacokinetics to assess in vivo to assess in vivo

Methods: in vitro skin Methods: in vitro skin permeationpermeation

Determined by Determined by Franz diffusion cellFranz diffusion cell

Skin of rat on a Skin of rat on a receptor receptor compartment with compartment with SC-side facing the SC-side facing the donor compartmentdonor compartment

Donor compartment Donor compartment filled with test drugfilled with test drug

In vitro permeation of In vitro permeation of capsaicin across rat capsaicin across rat skinskin

Capsaicin Capsaicin permeation permeation across rat skin across rat skin from study from study hydrogel is hydrogel is consistent with consistent with Dr. Fang’s Dr. Fang’s previous studies previous studies

Time (h)

0 10 20 30 40

Cumulative amount (

μ/g cm

2)

0

10

20

30

40

50

Methods: skin erythema Methods: skin erythema determinationdetermination

SC removedSC removed Mexemeter Mexemeter

placed on treated placed on treated skin surfaceskin surface

Result of Result of erythema was erythema was difference from difference from control value at control value at untreated siteuntreated site

Safety analysisSafety analysis

Skin condition Value ∆ Valuea

a* (skin erythema) -0.61±0.53

-1.28±2.13

Transepidermal water loss (g/m2/h)

13.19±2.42

1.23±2.47

a ∆ value indicates the value of patch-treated skin area minus the non-treated skin area (control).

Evaluation question and Evaluation question and standardstandard

Evaluation Evaluation QuestionQuestion

Does a topical Does a topical capsaicin 500 mcg capsaicin 500 mcg patch applied to 2 patch applied to 2 trigger points 12h trigger points 12h on and 12h off on and 12h off each day for 1 each day for 1 month improve month improve quality of life in quality of life in patients with patients with myofascial pain myofascial pain relative to a relative to a matched sample matched sample with placebowith placebo

StandardStandard

Statistically Statistically significant significant in in post-intervention post-intervention scores on quality scores on quality of life instrument of life instrument (global as well as (global as well as pain specific) and pain specific) and VAS relative to VAS relative to placeboplacebo

60 patients with chronic neck pain will be randomized into 2 groups of 30

Phase 1 Phase 2PLACEBO

TREATMENT

PLACEBO

TREATMENT

30 patients will apply gel without capsaicin 12h on 12h off x 4 weeks

30 patients will apply gel with capsaicin 12h on 12h off x 4 weeks

4- week wash out

30 patients will apply gel without capsaicin 12h on 12h off x 4 weeks

30 patients will apply gel with capsaicin 12h on 12h off x 4 weeks

McGill Pain Inventory, VAS, SF-36

McGill Pain Inventory, VAS, SF-36

McGill Pain Inventory, VAS, SF-36

McGill Pain Inventory, VAS, SF-36

Double-blinded, randomized controlled crossover design