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Welcome to issue 57 of Pain Management Research Review.The first research paper selected for this issue found that combining three nonopioid analgesics with morphine for postoperative analgesia provided better analgesia with significant morphine-sparing over 48 hours postsurgery when compared with morphine alone. An oromucosal spray containing THC (Δ9-tetrahydrocannabinol) and cannabidiol was found to be effective and well tolerated when used as add-on treatment for refractory chronic pain, with the effect particularly promising in neuropathic pain. A prospective 2-year trial has addressed the question of opioid efficacy for chronic noncancer pain, finding limited effectiveness as long-term management. A post hoc analysis of the TOPCARE (Transforming Opioid Prescribing in Primary Care) study has identified reasons for opioid discontinuation and associated outcomes.

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Dr Tim Hotim.ho@researchreview.com.au

Multicentre, prospective, double-blind, randomised controlled clinical trial comparing different non-opioid analgesic combinations with morphine for postoperative analgesiaAuthors: Beloeil H et al., the OCTOPUS group

Summary: The OCTOPUS study randomised 237 hospital patients to receive intravenous paracetamol (acetaminophen), nefopam, ketoprofen, any combination (including all three) or saline 4 times per day for 48 hours as postoperative analgesia; rescue analgesia was provided as patient-controlled morphine. Recipients of all three analgesics had significantly lower median morphine consumption over 24 hours compared with saline and nefopam monotherapy recipients (5 vs. 27 and 21mg, respectively [p<0.05]), with similar results at 48 hours postsurgery, and less pain compared with saline, nefopam monotherapy and paracetamol monotherapy recipients; the incidences of morphine-related side effects did not differ significantly.

Comment: This is a multicentre double-blind RCT (n=237) of patients undergoing a variety of major surgeries showing improved analgesia and significant reductions in morphine consumption in the combined adjuvants group (paracetamol 4 g/24h, nefopam 80 mg/24h and ketoprofen 200 mg/24h) versus the control group and the single adjuvant groups at 48 hours. Nefopam is a nonsedative benzoxazocine central-acting analgesia with noradrenaline (norepinephrine)/serotonin, dopamine-reuptake inhibition and anticonvulsant action. It is not available in Australia. I note that the recruitment for each group was low (25–32) resulting in lower power. RCTs on the efficacy of multi-adjuvant therapy in acute pain settings are scarce; however, this study is validating. I look forward to further high-powered RCTs.

Reference: Br J Anaesth 2019;122:98–106Abstract

Greater analgesic effect with intermittent compared with continuous mode of lumbar plexus block for total hip arthroplastyAuthors: Ueshima H et al.

Summary: Adults scheduled for THA (total hip arthroplasty) were randomised to perioperative analgesia with a 6 mL/hour continuous infusion of 0.125% levobupivacaine in lumbar plexus block (n=20) or 12mL infusions of 0.125% levobupivacaine every 2 hours in lumbar plexus block (n=20). Compared with continuous levobupivacaine infusions, intermittent infusions were associated with lower cumulative fentanyl consumption for rescue analgesia (primary outcome; 81.5 vs. 438µg [p<0.001]), lower numbers of demanded and delivered fentanyl boluses for rescue analgesia (p<0.001) and lower VAS pain scores except at postoperative hours 1 and 12 (p<0.05). Intermittent infusions were associated with constant sensory blockade, but the extent gradually narrowed with continuous infusions.

Comment: This is a randomised double-blind study (n=40) of THA patients showing significantly lower rescue fentanyl demand in the intermittent infusion group (12mL bolus 0.125% levobupivacaine every 2 hours) versus the continuous lumbar plexus block (6 mL/h 0.125% levobupivacaine) at 48 hours. Sensory block was checked using dermatomes rather than individual nerves. Perhaps in the case of lumbar plexus block, the spread of the larger volume bolus of local anaesthetics in a fascial compartment better covers the relevant lumbar plexus nerves (i.e., femoral, obturator and lateral femoral cutaneous nerve distribution). However, it would be interesting to compare the outcome to a single bolus block with that of liposomal bupivacaine, given this would negate potential catheter-related complications.

Reference: Reg Anesth Pain Med 2019;44:632–6Abstract

LBP = lower back pain; MCS = motor cortex stimulation;PNS = peripheral nerve stimulation; RCT = randomised clinical trial;THA = total hip arthroplasty; THC = Δ9-tetrahydrocannabinol;VAS = visual analogue scale.

Abbreviations used in this issue:

In this issue: > Different nonopioid analgesic combinations with morphine for postoperative analgesia

> Analgesia greater with intermittent- vs. continuous-mode lumbar plexus block in THA

> Percutaneous PNS for chronic neuropathic postamputation pain

> Add-on THC-cannabidiol oromucosal spray for severe chronic pain

> Opioid effectiveness in chronic noncancer pain

> Tonic vs. burst MCS in chronic neuropathic pain

> Emotional and attitudinal responses to simulated opioid-tapering advice

> Integrated functional-contextual framework for cognitive biases in pain

> Opioid discontinuation and subsequent unintended consequences in TOPCARE

> Cross-network connectivity in chronic pain

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Independent commentary by Dr Tim Ho, who is a rehabilitation and pain specialist at Inner West Pain Centre. Tim also works in work capacity centre and addiction medicine. His interests are chronic musculoskeletal pain, neuropathic pain, visceral pain and headache. His research interests are management of comorbid chronic pain and addiction, return-to-work programmes, osseointegration and nursing home resident pain management.

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Effectiveness of opioids for chronic noncancer painAuthors: Veiga DR et al.Summary: This 2-year study with propensity score matching evaluated long-term opioid effectiveness in chronic noncancer pain in a prospective cohort of 529 consecutive adults. The opioid prescribing rate was 59.7% at baseline and 70.3% at 2 years; 42.7% of opioid prescriptions were for strong opioids. Compared with opioid nonusers, opioid users reported no significant improvement in pain symptoms, physical function, emotional function or social/familiar disability. Opioid users did report greater satisfaction with care and outcomes at 1 year, but only satisfaction with outcomes was improved at 2 years.

Comment: There is insufficient evidence on the long-term efficacy of opioids for chronic noncancer pain. Previous studies have been limited by heterogeneity in study design, lack of functional data, small sample sizes and short-term follow-up (3–6 months). This is a multicentre, prospective cohort study of propensity score-matched cohorts (371 opioid users and 117 propensity score-matched nonopioid users) showing no improvement in functional outcome or quality of life in chronic noncancer pain patients prescribed opioids over 2 years of follow-up. Propensity score matching allows balanced conditional distribution of pretreatment characteristics, resulting in an unbiased comparison. Interestingly, patient satisfaction was higher in the opioid users at 12 months and 24 months. However, satisfaction is interpreted as a subjective evaluation of care rather than actual pain reduction or functional improvement. These data would be useful for clinical decision making and patient education.

Reference: J Pain 2019;20:706–15Abstract

Effectiveness of tonic and burst motor cortex stimulation in chronic neuropathic painAuthors: Sokal P et al.Summary: These authors reported on three patients with thalamic pain and three with facial pain who had undergone MCS (motor cortex stimulation) using both burst and tonic modes. The patients were asked to identify which mode was better for pain relief using VAS scores before replacement of the implanted pulse generator and after stimulation with tonic and burst modes. Five of the patients reported a preference for burst-mode MCS over the tonic mode. The baseline VAS score for patients who had ≥3 months depleted battery of tonic implanted pulse generator was 95mm, and after implantation of a new pulse generator, the respective mean VAS scores on tonic- and burst-mode stimulation were 72mm and 53mm.

Comment: Long-term motor cortex tonic stimulation may be limited by habituation on stimulation, causing a diminished analgesic effect. Motor cortex tonic stimulation involves stimulation at a frequency of 10–50Hz and amplitude of 1–10mA, and efficacy is dependent on amplitude, diversification of cyclisation and diversification. Burst stimulation with 500Hz spike mode 40 times per second mimics thalamus burst firing in tinnitus and pain. MCS both with tonic and burst generally do not induce paraesthesia. This is a case series of patients with neuropathic pain (three with thalamic pain and three with trigeminal neuropathy) with habituation to tonic stimulation showing further pain reduction with burst stimulation at 4 weeks. I note the small sample size and lack of randomisation and blinding, which may affect reliability. Further validation study is warranted.

Reference: J Pain Res 2019;12:1863–9Abstract

Percutaneous peripheral nerve stimulation for the treatment of chronic neuropathic postamputation painAuthors: Gilmore C et al.Summary: Lower-extremity amputees with postamputation pain (n=28) underwent ultrasound-guided implantation of percutaneous PNS (peripheral nerve stimulation) leads and were randomised to receive PNS or placebo for 4 weeks, after which the placebo group were crossed over to PNS, with all participants receiving PNS for 4 additional weeks. Compared with the placebo group, PNS recipients achieved a ≥50% reduction in average postamputation pain during weeks 1–4 (primary efficacy endpoint; 58% vs. 14%) and also at 8 weeks (67% vs. 14%), at which time a significantly greater proportion of PNS recipients had also achieved a ≥50% reduction in pain interference (80% vs. 15%). Four of five PNS recipients who had completed 12-month follow-up at the time of reporting had achieved ≥50% pain relief.

Comment: This is a multicentre, randomised, placebo-controlled, partial crossover trial (n=28) of patients with chronic neuropathic pain after lower-limb amputation (stump and phantom) showing significant improvement in pain interferences/global impression of change, and opioid medication reduction and pain/functional improvement in the patients on opioid medication, for a reversible PNS group (tonic stimulation) at 8 weeks. The responder rate was 67% with an average pain reduction of 62% at 8 weeks for the PNS group (vs. a 14% responder rate for the placebo group). I note the reduction of opioid usage was 0.8% for the placebo group and 48% for the PNS group at 4 weeks (71% for the PNS group at 8 weeks). I look forward to further prospective follow-up long-term data of this study.

Reference: Reg Anesth Pain Med 2019;44:637–45Abstract

Effectiveness and tolerability of THC:CBD oromucosal spray as add-on measure in patients with severe chronic painAuthors: Ueberall MA et al.Summary: This exploratory analysis of real-world 12-week data from the German Pain e-Registry was undertaken to evaluate the effectiveness, tolerability and safety of an oromucosal spray containing THC and cannabidiol as add-on treatment for severe chronic pain. There were 800 patients included who received such treatment in 2017. Treatment with THC-cannabidiol was associated with a 39.0% improvement from baseline in ASR-9 (aggregated nine-factor symptom relief) after 12 weeks, with 15.4% of patients achieving a 50% improvement in all nine factors and 56.0% achieving a ≥50% improvement in ≥5 factors. Improvements were significantly better in patients with neuropathic pain than in those with mixed or nociceptive pain. The proportion of patients who reported ≥1 treatment-emergent adverse event was 19.9% (81.6% mild intensity), most frequently increased appetite (6.3%) and dysgeusia (2.9%). The proportion of patients who discontinued treatment due to treatment-emergent adverse events was 4.0%, and 14.1% discontinued because of inadequate pain relief, 74.1% of whom had nociceptive pain compared with 0.2% of those with neuropathic pain (p<0.001).

Comment: This is a cohort study of real-world data (pain treatment registry for the German Pain Association; n=800) of severe refractory chronic pain patients (average pain duration 2.7 years) of add-on therapy of THC-cannabidiol oromucosal spray (THC 2.7mg and cannabidiol 2.5mg at 8–12 sprays per day) showing significant improvements in full and partial ASR-9 responses (>50% improvement in nine factors), especially in neuropathic pain at 12 weeks. I note that 4% of discontinuations were due to reported side effects, and 14% were due to inadequate pain relief, mostly in patients with nociceptive pain. This is in contrast to some RCTs showing minor additional effects compared with placebo. The short-term data and the lack of a placebo or active control may present issues for its internal and external validity. Further RCTs are warranted to substantiate the results.

Reference: J Pain Res 2019;12:1577–604Abstract

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MINIMUM PRODUCT INFORMATION: PALEXIA® SR (tapentadol hydrochloride) INDICATION: SR (tapentadol hydrochloride) INDICATION: Moderate to severe chronic pain unresponsive to non-narcotic analgesia. CONTRAINDICATIONS: Known hypersensitivity to tapentadol or any component of PALEXIA SR; conditions in which mu-opioid receptor agonist activity is contraindicated Known hypersensitivity to tapentadol or any component of PALEXIA SR; conditions in which mu-opioid receptor agonist activity is contraindicated e.g. significant respiratory depression and acute or severe bronchial asthma or hypercapnia; confirmed or suspected paralytic ileus; acute intoxication with alcohol; hypnotics, e.g. significant respiratory depression and acute or severe bronchial asthma or hypercapnia; confirmed or suspected paralytic ileus; acute intoxication with alcohol; hypnotics, centrally acting analgesics or psychotropic drugs; patients who are receiving MAO inhibitors or who have taken them within the last 14 days. centrally acting analgesics or psychotropic drugs; patients who are receiving MAO inhibitors or who have taken them within the last 14 days. PRECAUTIONS: Monitor for signs of abuse and addiction; repeated administration may lead to tolerance; withdrawal symptoms could occur after abrupt discontinuation; not recommended in patients signs of abuse and addiction; repeated administration may lead to tolerance; withdrawal symptoms could occur after abrupt discontinuation; not recommended in patients with increased intracranial pressure, impaired consciousness, or coma and severe renal or severe hepatic impairment; caution in patients with impaired respiratory functions, with increased intracranial pressure, impaired consciousness, or coma and severe renal or severe hepatic impairment; caution in patients with impaired respiratory functions, patients with head injury, brain tumours, a history of seizures or any condition that increases risk of seizures, moderate hepatic impairment or biliary tract disease, including patients with head injury, brain tumours, a history of seizures or any condition that increases risk of seizures, moderate hepatic impairment or biliary tract disease, including acute pancreatitis. Use in pregnancy (Category C). Should not be used during breastfeeding. Not recommended for children <18 years old. May impair ability to drive or acute pancreatitis. Use in pregnancy (Category C). Should not be used during breastfeeding. Not recommended for children <18 years old. May impair ability to drive or operate machinery. INTERACTIONS: Care should be taken when combining with mixed opioid agonist/antagonists or partial mu-opioid agonists; additive CNS depression Care should be taken when combining with mixed opioid agonist/antagonists or partial mu-opioid agonists; additive CNS depression with concomitant administration of other mu-opioid receptor agonist analgesics, general anaesthetics, phenothiazines, other tranquilisers, sedatives, hypnotics or other CNS with concomitant administration of other mu-opioid receptor agonist analgesics, general anaesthetics, phenothiazines, other tranquilisers, sedatives, hypnotics or other CNS depressants (including alcohol and illicit drugs) – reduction of dose of one or both agents should be considered; contraindicated in patients who are receiving MAO inhibitors depressants (including alcohol and illicit drugs) – reduction of dose of one or both agents should be considered; contraindicated in patients who are receiving MAO inhibitors or who have taken them within the last 14 days; isolated case reports of serotonin syndrome when used in combination with serotonergic drugs (see full PI). or who have taken them within the last 14 days; isolated case reports of serotonin syndrome when used in combination with serotonergic drugs (see full PI). ADVERSE EFFECTS: Very common (≥1/10): dizziness, somnolence, headache, nausea, constipation; Common (1/10): dizziness, somnolence, headache, nausea, constipation; Common (≥1/100 to <1/10): Decreased appetite, anxiety, depressed mood, sleep disorder, nervousness, restlessness, disturbance in attention, tremor, muscle contractions involuntary, flushing, dyspnoea, vomiting, diarrhoea, dyspepsia, pruritus, hyperhidrosis, disorder, nervousness, restlessness, disturbance in attention, tremor, muscle contractions involuntary, flushing, dyspnoea, vomiting, diarrhoea, dyspepsia, pruritus, hyperhidrosis, rash, asthenia, fatigue, feeling of body temperature change, mucosal dryness, oedema. Postmarketing: suicidal ideation, angioedema, anaphylaxis and anaphylactic shock. rash, asthenia, fatigue, feeling of body temperature change, mucosal dryness, oedema. Postmarketing: suicidal ideation, angioedema, anaphylaxis and anaphylactic shock. DOSAGE AND ADMINISTRATION: To be taken orally twice daily, whole with sufficient liquid, approximately every twelve hours, with or without food. Initiation of therapy in To be taken orally twice daily, whole with sufficient liquid, approximately every twelve hours, with or without food. Initiation of therapy in patients currently not taking opioid analgesics: start with 50 mg PALEXIA SR twice daily. Initiation of therapy in patients currently taking opioid analgesics: nature, administration patients currently not taking opioid analgesics: start with 50 mg PALEXIA SR twice daily. Initiation of therapy in patients currently taking opioid analgesics: nature, administration and mean daily dose of previous medication should be taken into account. Titration and maintenance: titrate individually to a level that provides adequate analgesia and minimises and mean daily dose of previous medication should be taken into account. Titration and maintenance: titrate individually to a level that provides adequate analgesia and minimises side effects under close supervision of prescribing physician; titration regimen in increments of 50 mg twice daily every 3 days shown to be appropriate in most patients in side effects under close supervision of prescribing physician; titration regimen in increments of 50 mg twice daily every 3 days shown to be appropriate in most patients in clinical trials. Total daily doses > 500 mg not recommended. Discontinuation of treatment: taper dose gradually to prevent symptoms of withdrawal. Renal Impairment: clinical trials. Total daily doses > 500 mg not recommended. Discontinuation of treatment: taper dose gradually to prevent symptoms of withdrawal. Renal Impairment: not recommended in severe renal impairment. Hepatic Impairment: initiate at 50 mg once daily in moderate hepatic impairment; not recommended in severe hepatic not recommended in severe renal impairment. Hepatic Impairment: initiate at 50 mg once daily in moderate hepatic impairment; not recommended in severe hepatic impairment. Elderly patients more likely to have decreased renal and hepatic function – care in dose selection. Not recommended for use in children <18 years old. impairment. Elderly patients more likely to have decreased renal and hepatic function – care in dose selection. Not recommended for use in children <18 years old. Based on approved Product Information dated 27 March 2017Based on approved Product Information dated 27 March 2017. REFERENCES: 1. PALEXIA SR Approved Product Information. 2. Schug S. ANZCA Bulletin 2018. Not all opioids are the same. 3. Raffa RB. Curr Med Res OpinCurr Med Res Opin 2014: 30(12):2579–2584. Curr Med Res Opin 2014: 30(12):2579–2584. Curr Med Res Opin 4. Pergolizzi J et al. NEMA Research Group, Naples, Florida, USA 2017.5. Lange B et al. Adv Ther 2010; 27(6):381–399. et al. Adv Ther 2010; 27(6):381–399. et al. Adv Ther 6. Grünenthal, Data on File: GRT-UK-DOF-001. PALEXIA Grünenthal, Data on File: GRT-UK-DOF-001. PALEXIA® SR is a registered trademark of Grünenthal Pty Ltd. PALEXIA®

et al. NEMA Research Group, Naples, Florida, USA 2017.®

et al. NEMA Research Group, Naples, Florida, USA 2017. SR is distributed by

Seqirus (Australia) Pty Ltd under licence from Grünenthal Pty Ltd. Seqirus (Australia) Pty Ltd ABN 66 120 398 067, 63 Poplar Road Parkville, Victoria 3052. Seqirus (Australia) Pty Ltd under licence from Grünenthal Pty Ltd. Seqirus (Australia) Pty Ltd ABN 66 120 398 067, 63 Poplar Road Parkville, Victoria 3052. www.seqirus.com.au. Medical Information: 1800 642 865. Seqirus™ is a trademark of Seqirus UK Limited or its af� liates. Date of preparation: www.seqirus.com.au. Medical Information: 1800 642 865. Seqirus™ is a trademark of Seqirus UK Limited or its af� liates. Date of preparation: February 2019. SEQ/PALX/0119/0559. 15004.

PBS Information: Restricted bene� t. Chronic severe disabling pain not responding to non-narcotic analgesics. Authority required for increased maximum quantities and/or repeats. Refer to PBS schedule for full restricted bene� t and authority information.

Before prescribing, please review the Product Information available at www.seqirus.com.au/PIBefore prescribing, please review the Product Information available at www.seqirus.com.au/PI

ATYPICAL OPIOID1–4*

EVERYDAY BENEFITS1,5,6

• Strong^ pain relief as effective as oxycodone CR1,5#

• Significantly less constipation, nausea and vomiting vs. oxycodone CR1,5#

• Significantly greater improvement in functional outcomes† vs. oxycodone CR5,6#

*Analgesia not solely derived from opioid agonism. ^S8 analgesic. *Analgesia not solely derived from opioid agonism. ^S8 analgesic. #Meta-analysis to assess non-inferior ef� cacy and tolerability in moderate to #Meta-analysis to assess non-inferior ef� cacy and tolerability in moderate to severe pain (p<0.001 for all events) in patients with chronic knee osteoarthritis or low severe pain (p<0.001 for all events) in patients with chronic knee osteoarthritis or low back pain. †In Physical and Social Functioning and Role Physical (SF-36 outcomes, p ≤ 0.008).back pain. †In Physical and Social Functioning and Role Physical (SF-36 outcomes, p ≤ 0.008).

FOR PATIENTS WITH MODERATE TO SEVERE CHRONIC PAIN:1

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Reasons for opioid discontinuation and unintended consequences following opioid discontinuation within the TOPCARE trialAuthors: Husain JM et al.

Summary: Reasons for opioid discontinuation and outcomes following discontinuation were reported for participants from the TOPCARE study, which compared an intervention of nurse care manager support, an electronic registry, academic detailing and electronic tools (n=586) with controls (n=399); randomisation was by primary-care provider. The respective opioid discontinuation rates for the intervention and control groups were 14.2% and 10.5% (p=0.09). Opioid misuse was the reason for discontinuation in 65% of participants, mostly due to monitoring aberrancies, with no significant between-group difference. Primary-care provider follow-up was lower in intervention participants who discontinued opioids compared with controls (65% vs. 88% [p<0.01]). There was no significant between-group difference for pain-related emergency department visits, evidence of opioid use disorder or referral for opioid use disorder treatment following discontinuation.

Comment: This is a post hoc retrospective chart review (n=985) of patients who discontinued opioids in the TOPCARE intervention in the primary-care setting, showing 14% opioid discontinuations in the intervention arm and 10% in the control arm. Presumed opioid misuse accounted for the majority of opioid discontinuations. Interestingly, general practitioner follow-up in the intervention group who discontinued opioids was only 65% (compared with 88% in controls), suggesting poor engagement after deprescribing, which was unintended. Strategies to better engage patients following opioid discontinuation, such as pain management programmes and substance use treatment, are needed. Further study is warranted.

Reference: Pain Med 2019;20:1330–7Abstract

Somatotopically specific primary somatosensory connectivity to salience and default mode networks encodes clinical painAuthors: Kim J et al.

Summary: Healthy adults and patients with chronic LBP (lower back pain; n=181) were evaluated at baseline and after performing physical manoeuvres that exacerbated pain to investigate the link between brain connectivity and clinical pain intensity. Compared with healthy adults, patients with chronic LBP showed greater connectivity between the functionally localised back representation in the primary somatosensory cortex and both the salience network and the default mode network. Pain exacerbation manoeuvres were associated with increased connectivity between functionally localised back representation in the primary somatosensory cortex and salience network regions, but connectivity to the default mode network was decreased; greater pain intensity increases were associated with greater shifts in these connectivity patterns. Connectivity between the default mode network and the anterior insula cortex (a cardinal node of the salience network), which correlated with increased postmanoeuvre pain, was only seen in patients with chronic LBP who reported high pain catastrophising.

Comment: This is a cohort study (n=181) of chronic LBP patients showing increased S1 (back) connectivity to both the salient network and default mode network on functional MRI. Pain exacerbation manoeuvres were shown to increase salient network connectivity, but reduced default mode network connectivity. High catastrophisation was shown to be associated with increased default mode network connectivity to the cardinal node of the salient network (anterior/middle insula). This suggests that the change in connectivity between S1 and the salient network (especially anterior insula) and default mode network likely further allocates attentional/affective coding to the somatic nociceptive coding. It will be interesting to see if a change in catastrophisation and pain reactivity (e.g. with a pain management programme) would influence this connectivity.

Reference: Pain 2019;160:1594–605Abstract

Time for change: an experimental investigation of chronic pain patients’ emotional and attitudinal responses to simulated opioid-tapering adviceAuthors: Ashton-James CE et al.

Summary: This research examined emotional and attitudinal responses to simulated opioid-tapering advice in 196 patients presenting to a tertiary pain clinic with chronic pain for the first time. The participants were randomised to view video footage of a standardised patient receiving one of the following three forms of treatment advice: i) stay on current medication; ii) change to a different pain medication; or iii) taper off pain medications and participate in a cognitive behavioural therapy-based pain self-management programme. The participants expressed positive emotional and attitudinal responses to simulated opioid-tapering advice more often than they did to simulated opioid-maintenance advice. Furthermore, their responses to simulated opioid-tapering advice and advice to change their opioid did not differ significantly. Participants with a longer history of chronic pain and opioid use generally provided less positive responses to simulated opioid-tapering advice.

Comment: This is a prospective cohort study (n=196) of chronic pain patients on opioid medications showing more positive emotional and attitudinal responses to simulated opioid tapering advice and an alternative approach than to simulated opioid maintenance advice. Furthermore, duration of opioid use and chronic pain predicted negative emotions/attitudes, such as anger/irritation to opioid-tapering advice. It is difficult to generalise the findings to advice that was delivered by the treating clinician (which may be more consequential). Negative emotion may be evoked by implementation of opioid tapering due to pessimism about the efficacy of the nonpharmacological approach, fear of opioid withdrawal and concern of abandonment. Further pragmatic study is warranted.

Reference: Pain 2019;160:1586–93Abstract

Cognitive biases in pain: an integrated functional-contextual frameworkAuthors: Van Ryckeghem DML et al.

Summary: These authors reviewed cognitive biases in the context of pain. They covered the state of the science with respect to the presence and impact of cognitive biases in pain. They also presented a comprehensive discussion on the importance of an integrated functional-contextual framework for understanding the cognitive biases, highlighting that they are both functional and dynamic phenomena, and inter-related. The review also discussed the future research agenda for cognitive bias research, and finished up discussing clinical implications.

Comment: This is a topical review by Dimitri Van Ryckeghem and colleagues discussing cognitive biases for chronic pain using an integrated functional-contextual framework. There is limited evidence suggesting that maladaptive cognitive biases, such as attention bias, interpretation bias and memory bias, perpetuating chronic pain and related disability. Cognitive biases are functional and dynamic phenomena and usually have an underlying mechanism of action, and flexible adaptation to the cognitive bias may occur with executive control (mental flexibility), which is driven by motivation in a personal context and influenced by pain-relevant goal pursuit. Hence, effective treatment should address cognitive bias in the functional and contextual framework. I look forward to further translational study on this topic.

Reference: Pain 2019;160:1489–93Abstract

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