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Smoked cannabis for chronic neuropathic pain: a randomized controlled trial.
Ware MA, Wang T, Shapiro S, et al.
CMAJ. 2010 Oct 5;182(14):E694-701.
BACKGROUND: Chronic neuropathic pain affects 1%-2% of the adult population and is often refractory to standard pharmacologic treatment. Patients with chronic pain have reported using smoked cannabis to relieve pain, improve sleep and improve mood. METHODS: Adults with post-traumatic or postsurgical neuropathic pain were randomly assigned to receive cannabis at four potencies (0%, 2.5%, 6% and 9.4% tetrahydrocannabinol) over four 14-day periods in a crossover trial. Participants inhaled a single 25-mg dose through a pipe three times daily for the first five days in each cycle, followed by a nine-day washout period. Daily average pain intensity was measured using an 11-point numeric rating scale. We recorded effects on mood, sleep and quality of life, as well as adverse events. RESULTS: We recruited 23 participants (mean age 45.4 [standard deviation 12.3] years, 12 women [52%]), of whom 21 completed the trial. The average daily pain intensity, measured on the 11-point numeric rating scale, was lower on the prespecified primary contrast of 9.4% v. 0% tetrahydrocannabinol (5.4 v. 6.1, respectively; difference = 0.7, 95% confidence interval [CI] 0.02-1.4). Preparations with intermediate potency yielded intermediate but nonsignificant degrees of relief. Participants receiving 9.4% tetrahydrocannabinol reported improved ability to fall asleep (easier, p = 0.001; faster, p < 0.001; more drowsy, p = 0.003) and improved quality of sleep (less wakefulness, p = 0.01) relative to 0% tetrahydrocannabinol. We found no differences in mood or quality of life. The most common drug-related adverse events during the period when participants received 9.4% tetrahydrocannabinol were headache, dry eyes, burning sensation in areas of neuropathic pain, dizziness, numbness and cough. CONCLUSION: A single inhalation of 25 mg of 9.4% tetrahydrocannabinol herbal cannabis three times daily for five days reduced the intensity of pain, improved sleep and was well tolerated. Further long-term safety and efficacy studies are indicated. (International Standard Randomised Controlled Trial Register no. ISRCTN68314063).
Ware MA, Wang T, Shapiro S, et al.
CMAJ. 2010 Oct 5;182(14):E694-701.
BACKGROUND: Chronic neuropathic pain affects 1%-2% of the adult population and is often refractory to standard pharmacologic treatment. Patients with chronic pain have reported using smoked cannabis to relieve pain, improve sleep and improve mood. METHODS: Adults with post-traumatic or postsurgical neuropathic pain were randomly assigned to receive cannabis at four potencies (0%, 2.5%, 6% and 9.4% tetrahydrocannabinol) over four 14-day periods in a crossover trial. Participants inhaled a single 25-mg dose through a pipe three times daily for the first five days in each cycle, followed by a nine-day washout period. Daily average pain intensity was measured using an 11-point numeric rating scale. We recorded effects on mood, sleep and quality of life, as well as adverse events. RESULTS: We recruited 23 participants (mean age 45.4 [standard deviation 12. -
Reassessment of neuropathic pain in light of its revised definition: Possible implications and consequences.
Eisenberg E.
Pain. 2010 Aug 5.
Eisenberg E.
Pain. 2010 Aug 5. -
Racial disparity in analgesic treatment for ED patients with abdominal or back pain.
Mills AM, Shofer FS, Boulis AK, et al.
Am J Emerg Med. 2010 Apr 30.
OBJECTIVE: Research on how race affects access to analgesia in the emergency department (ED) has yielded conflicting results. We assessed whether patient race affects analgesia administration for patients presenting with back or abdominal pain. METHODS: This is a retrospective cohort study of adults who presented to 2 urban EDs with back or abdominal pain for a 4-year period. To assess differences in analgesia administration and time to analgesia between races, Fisher exact and Wilcoxon rank sum test were used, respectively. Relative risk regression was used to adjust for potential confounders. RESULTS: Of 20 125 patients included (mean age, 42 years; 64% female; 75% black; mean pain score, 7.5), 6218 (31%) had back pain and 13 907 (69%) abdominal pain. Overall, 12 109 patients (60%) received any analgesia and 8475 (42%) received opiates. Comparing nonwhite (77 %) to white patients (23%), nonwhites were more likely to report severe pain (pain score, 9-10) (42% vs 36%; P < .0001) yet less likely to receive any analgesia (59% vs 66%; P < .0001) and less likely to receive an opiate (39% vs 51%; P < .0001). After controlling for age, sex, presenting complaint, triage class, admission, and severe pain, white patients were still 10% more likely to receive opiates (relative risk, 1.10; 95% confidence interval, 1.06-1.13). Of patients who received analgesia, nonwhites waited longer for opiate analgesia (median time, 98 vs 90 minutes; P = .004). CONCLUSIONS: After controlling for potential confounders, nonwhite patients who presented to the ED for abdominal or back pain were less likely than whites to receive analgesia and waited longer for their opiate medication.
Mills AM, Shofer FS, Boulis AK, et al.
Am J Emerg Med. 2010 Apr 30.
OBJECTIVE: Research on how race affects access to analgesia in the emergency department (ED) has yielded conflicting results. We assessed whether patient race affects analgesia administration for patients presenting with back or abdominal pain. METHODS: This is a retrospective cohort study of adults who presented to 2 urban EDs with back or abdominal pain for a 4-year period. To assess differences in analgesia administration and time to analgesia between races, Fisher exact and Wilcoxon rank sum test were used, respectively. Relative risk regression was used to adjust for potential confounders. RESULTS: Of 20 125 patients included (mean age, 42 years; 64% female; 75% black; mean pain score, 7.5), 6218 (31%) had back pain and 13 907 (69%) abdominal pain. Overall, 12 109 patients (60%) received any analgesia and 8475 (42%) received opiates. -
Oxycodone improves pain and quality of life in anticonvulsant-pretreated spinal cord-injured patients with neuropathic pain
Barrera-Chacon JM, Mendez-Suarez JL, Jáuregui-Abrisqueta ML, et al.
Spinal Cord. 2010 Sep 7.
Study design:A 3-month follow-up, observational, prospective, multicenter, study in traumatic spinal cord-injured (SCI) patients with neuropathic pain (NP).Objectives:To assess the effectiveness and safety of oxycodone treatment in SCI patients with anticonvulsants-refractory NP.Setting:'Spinal injury follow-up units' throughout Spain.Methods:Data regarding NP characteristics were collated from male and female adults with traumatic SCI and difficult-to-control central NP of moderate-to-severe intensity (visual analog scale (VAS) >/=4) persisting >/=1 month, who had been para- or tetraplegic for >/=2 months, had been previously treated with anticonvulsants and were now treated with oxycodone.Results:In all, 54 out of the 57 patients recruited were assessable. A total of 81% were men and the mean age was 46.4. Patients were treated with oxycodone, 83% combined with anticonvulsant. Pain intensity (VAS: 7.1+/-1.3-4.3+/-1.7) and Lattinen total score (13.2+/-3-7.7+/-3.4) decreased significantly (P<0.001) along the study. No patient got worse regarding pain impact on physical activity and on sleep (Lattinen scale). EQ-5D VAS showed a trend to increase (P=0.061) and the index of preference values increased significantly from baseline to month 3 (0.26-0.62; P<0.001). A total of 53.7% patients showed at least one treatment-related adverse event, with constipation being the most frequent one (33.3%).Conclusion:Oxycodone treatment, mostly in combination with anticonvulsants, in SCI patients with NP decreases pain intensity, improves health-related quality of life and diminishes the impact of pain on physical activity and sleep.Sponsorship:This study has been sponsored by Mundipharma, SL, Madrid, Spain.Spinal Cord advance online publication, 7 September 2010; doi:10.1038/sc.2010.101.
Barrera-Chacon JM, Mendez-Suarez JL, Jáuregui-Abrisqueta ML, et al.
Spinal Cord. 2010 Sep 7.
Study design:A 3-month follow-up, observational, prospective, multicenter, study in traumatic spinal cord-injured (SCI) patients with neuropathic pain (NP).Objectives:To assess the effectiveness and safety of oxycodone treatment in SCI patients with anticonvulsants-refractory NP.Setting:'Spinal injury follow-up units' throughout Spain.Methods:Data regarding NP characteristics were collated from male and female adults with traumatic SCI and difficult-to-control central NP of moderate-to-severe intensity (visual analog scale (VAS) >/=4) persisting >/=1 month, who had been para- or tetraplegic for >/=2 months, had been previously treated with anticonvulsants and were now treated with oxycodone.Results:In all, 54 out of the 57 patients recruited were assessable. A total of 81% were men and the mean age was 46.4. -
Outcomes associated with opioid use in the treatment of chronic noncancer pain in older adults: a systematic review
Papaleontiou M, Henderson CR Jr, Turner BJ, et al.
J Am Geriatr Soc. 2010;58(7):1353-69.
This systematic review summarizes existing evidence regarding the efficacy, safety, and abuse and misuse potential of opioids as treatment for chronic noncancer pain in older adults. Multiple databases were searched to identify relevant studies published in English (1/1/80-7/1/09) with a mean study population age of 60 and older. Forty-three articles were identified and retained for review (40 reported safety and efficacy data, the remaining 3 reported misuse or abuse outcome data). The weighted mean subject age was 64.1 (mean age range 60-73). Studies enrolled patients with osteoarthritis (70%), neuropathic pain (13%), and other pain-producing disorders (17%). The mean duration of treatment studies was 4 weeks (range 1.5-156 weeks), and only five (12%) lasted longer than 12 weeks. In meta-analyses, effect sizes were -0.557 (P<.001) for pain reduction, -0.432 (P<.001) for physical disability reduction, and 0.859 (P=.31) for improved sleep. The effect size for the Medical Outcomes Study 36-item Health Survey was 0.191 (P=.17) for the physical component score and -0.220 (P=.04) for the mental component score. Adults aged 65 and older were as likely as those younger than 65 to benefit from treatment. Common adverse events included constipation (median frequency of occurrence 30%), nausea (28%), and dizziness (22%) and prompted opioid discontinuation in 25% of cases. Abuse and misuse behaviors were negatively associated with older age. In older adults with chronic pain and no significant comorbidity, short-term use of opioids is associated with reduction in pain intensity and better physical functioning but poorer mental health functioning. The long-term safety, efficacy, and abuse potential of this treatment practice in diverse populations of older persons remain to be determined.
Papaleontiou M, Henderson CR Jr, Turner BJ, et al.
J Am Geriatr Soc. 2010;58(7):1353-69.
This systematic review summarizes existing evidence regarding the efficacy, safety, and abuse and misuse potential of opioids as treatment for chronic noncancer pain in older adults. Multiple databases were searched to identify relevant studies published in English (1/1/80-7/1/09) with a mean study population age of 60 and older. Forty-three articles were identified and retained for review (40 reported safety and efficacy data, the remaining 3 reported misuse or abuse outcome data). The weighted mean subject age was 64.1 (mean age range 60-73). Studies enrolled patients with osteoarthritis (70%), neuropathic pain (13%), and other pain-producing disorders (17%). The mean duration of treatment studies was 4 weeks (range 1.5-156 weeks), and only five (12%) lasted longer than 12 weeks. In meta-analyses, effect sizes were -0.557 (P<.001) for pain reduction, -0. -
Systematic review: treatment agreements and urine drug testing to reduce opioid misuse in patients with chronic pain.
Starrels JL, Becker WC, Alford DP, et al.
Ann Intern Med. 2010 Jun 1;152(11):712-20.
BACKGROUND: Experts recommend opioid treatment agreements and urine drug testing to reduce opioid analgesia misuse, but evidence of their effectiveness has not been systematically reviewed. PURPOSE: To synthesize studies of the association of treatment agreements and urine drug testing with opioid misuse outcomes in outpatients with chronic noncancer pain. DATA SOURCES: MEDLINE, PsycINFO, EMBASE, Cochrane Central Register of Controlled Clinical Trials (January 1966 to June 2009), reference lists, and expert contacts. STUDY SELECTION: Original research addressing opioid medications, chronic pain, and treatment agreements or urine drug testing, with a sample size of 50 participants or more and published in English, Spanish, or French. DATA EXTRACTION: Two investigators independently identified eligible studies, extracted data, and assessed study quality. The outcome of opioid misuse was defined as drug abuse, drug misuse, aberrant drug-related behavior, diversion, or addiction. DATA SYNTHESIS: Of 102 eligible studies, 11 met inclusion criteria; 6 were in pain clinics and 5 were in primary care settings. Four primary care studies examined multicomponent strategies that included interdisciplinary support. All studies were observational and rated as poor to fair quality. In 4 studies with comparison groups, opioid misuse was modestly reduced (7% to 23%) after treatment agreements with or without urine drug testing. In the other 7 studies, the proportion of patients with opioid misuse after treatment agreements, urine drug testing, or both varied widely (3% to 43%). LIMITATIONS: Diversity of interventions and opioid misuse measures precluded meta-analysis. Most studies evaluated combinations of interventions. CONCLUSION: Relatively weak evidence supports the effectiveness of opioid treatment agreements and urine drug testing in reducing opioid misuse by patients with chronic pain. Further research on effective ways to monitor and reduce opioid misuse is needed, especially in primary care settings. PRIMARY FUNDING SOURCE: Substance Abuse and Mental Health Services Administration, National Institute on Drug Abuse, and Robert Wood Johnson Foundation.
Starrels JL, Becker WC, Alford DP, et al.
Ann Intern Med. 2010 Jun 1;152(11):712-20.
BACKGROUND: Experts recommend opioid treatment agreements and urine drug testing to reduce opioid analgesia misuse, but evidence of their effectiveness has not been systematically reviewed. PURPOSE: To synthesize studies of the association of treatment agreements and urine drug testing with opioid misuse outcomes in outpatients with chronic noncancer pain. DATA SOURCES: MEDLINE, PsycINFO, EMBASE, Cochrane Central Register of Controlled Clinical Trials (January 1966 to June 2009), reference lists, and expert contacts. STUDY SELECTION: Original research addressing opioid medications, chronic pain, and treatment agreements or urine drug testing, with a sample size of 50 participants or more and published in English, Spanish, or French. DATA EXTRACTION: Two investigators independently identified eligible studies, extracted data, and assessed study quality. -
Flushing following interlaminar lumbar epidural steroid injection with dexamethasone.
Kim CH, Issa MA, Vaglienti RM.
Pain Physician. 2010
BACKGROUND: Epidural steroid injections are commonly used in managing radicular pain. Most complications related to epidural injections are minor and self-limited. Flushing is considered as one such minor side effect. Flushing has been studied using various steroid preparations including methylprednisone, triamcinolone, and betamethasone but its frequency has never been studied using dexamethasone. OBJECTIVE: This study evaluates the frequency of flushing associated with fluoroscopy-guided lumbar epidural steroid injections using dexamethasone. STUDY DESIGN: Retrospective cohort design study. Patients presenting with low back pain were evaluated and offered a fluoroscopically guided lumbar epidural steroid injection using dexamethasone via an interlaminar approach as part of a conservative care treatment plan. SETTING: University-based Pain Management Center. INTERVENTION: All injections were performed consecutively over a 2-month period by one staff member using 16 mg (4 mg/mL) of dexamethasone. A staff physician specifically asked each participant about the presence of flushing following the procedure prior to discharge on the day of injection and again on follow-up within 48 hours after the injections. The answers were documented as "YES" or "NO." RESULTS: A total of 150 participants received fluoroscopically guided interlaminar epidural steroid injection. All participants received 16 mg (4 mg/mL) of dexamethasone with 2 mL of 0.2% ropiviciane. Overall incidence of flushing was 42 out of 150 cases (28%). Of the 42 participants who experienced flushing, 12 (28%) experienced the symptom prior to discharge following the procedure. Twenty-seven of the 42 (64%) were female (P < 0.05). All the participants who experienced flushing noted resolution by 48 hours. No other major side effects or complications were noted. LIMITATIONS: Follow-up data were solely based on subjective reports by patients via telecommunication. Follow-up time was limited to only 48 hours, which overlooks the possibility that more participants might have noted flushing after the 48 hour limit. CONCLUSIONS: Flushing is commonly reported following epidural steroid injections. With an incidence of 28%, injections using dexamethasone 16 mg by interlaminar epidural route appear to be associated with more flushing reaction than previously reported with other steroid preparations. Additionally, female participants are more likely to experience flushing though the reactions seem to be self-limiting with resolution by 48 hours.
Kim CH, Issa MA, Vaglienti RM.
Pain Physician. 2010
BACKGROUND: Epidural steroid injections are commonly used in managing radicular pain. Most complications related to epidural injections are minor and self-limited. Flushing is considered as one such minor side effect. Flushing has been studied using various steroid preparations including methylprednisone, triamcinolone, and betamethasone but its frequency has never been studied using dexamethasone. OBJECTIVE: This study evaluates the frequency of flushing associated with fluoroscopy-guided lumbar epidural steroid injections using dexamethasone. STUDY DESIGN: Retrospective cohort design study. Patients presenting with low back pain were evaluated and offered a fluoroscopically guided lumbar epidural steroid injection using dexamethasone via an interlaminar approach as part of a conservative care treatment plan. SETTING: University-based Pain Management Center. -
The genetics of pain: implications for evaluation and treatment of spinal disease.
Kim DH, Schwartz, CE.
Spine J. 2010;10(9):827-840.
BACKGROUND CONTEXT: Variability in human pain experience appears to be at least partially determined by genetic inheritance. To the extent that awareness of individual pain sensitivity and the tendency to develop chronic pain after injury or surgery would be informative for clinical decision making, development and use of genetic testing for specific pain markers could contribute to improved outcomes in management of spinal disease. PURPOSE: To review important and illustrative results from both classical and modern pain genetics studies and to introduce readers to critical definitions and concepts necessary to interpret the growing body of genetics literature relevant to spinal disease. STUDY DESIGN/SETTING: Literature review and commentary. METHODS: A review was performed of published English language studies in which genetic techniques were used to analyze the molecular basis of nociceptive signaling or processing with a particular emphasis on studies addressing genetic determinants of interindividual variability in pain sensitivity or predisposition to chronic pain. RESULTS: There is compelling evidence indicating that interindividual differences in pain sensitivity and the risk of developing chronic pain syndromes are genetically determined. Despite a growing list of putative "pain genes," genetic association studies remain plagued with difficulty replicating initial findings in different cohorts.CONCLUSIONS: Genome-wide association studies are potentially powerful means of identifying clinically relevant genetic markers predicting disease susceptibility, severity, and treatment response. However, accurate results require rigorous study design with use of large homogeneous populations and precise phenotypes.
Kim DH, Schwartz, CE.
Spine J. 2010;10(9):827-840.
BACKGROUND CONTEXT: Variability in human pain experience appears to be at least partially determined by genetic inheritance. To the extent that awareness of individual pain sensitivity and the tendency to develop chronic pain after injury or surgery would be informative for clinical decision making, development and use of genetic testing for specific pain markers could contribute to improved outcomes in management of spinal disease. PURPOSE: To review important and illustrative results from both classical and modern pain genetics studies and to introduce readers to critical definitions and concepts necessary to interpret the growing body of genetics literature relevant to spinal disease. STUDY DESIGN/SETTING: Literature review and commentary. -
Determinants of fentanyl and other potent micro opioid agonist misuse in opioid-dependent individuals.
Cicero TJ, Ellis MS, Paradis A, Ortbal Z.
Pharmacoepidemiol Drug Saf. 2010 Jul 1.
PURPOSE: Based on preclinical and clinical abuse liability assessments, fentanyl and other potent micro opioid agonists (e.g., hydromorphone and morphine) should be the most misused opioids if accessibility in the real world were not an issue. Since the latter is seldom true, we postulated that there would be a significant mismatch between actual and predicted rates of misuse. METHODS: We recruited 1818 prescription-opioid dependent patients entering drug treatment programs to complete an anonymous survey, covering drug use and health related issues. RESULTS: Hydrocodone and oxycodone products were the drugs of choice in 75% of patients, whereas potent micro opioid agonists (fentanyl, hydromorphone, and morphine), with the greatest predicted abuse potential, were very rarely chosen (<5% each). Most unexpectedly, the rank order of the actual drug of choice and the preferred drug in an ideal world were highly correlated. The reason most commonly given for the failure to endorse fentanyl, for example, as an actual or preferred drug, was fear of toxicity and overdose. We found few differences in drug use patterns between a subset of high-risk, impaired health care professionals (N = 196), and all other patients other than source of drug (forged prescriptions and doctors more common and dealers much less common in the HC sample). CONCLUSIONS: These results indicate that it should not be assumed - particularly for new drug formulations - that a high potential for abuse will result in actual abuse; and, most importantly, that the hesitancy to use potent opioids because of fears of abuse may be misguided. Copyright (c) 2010 John Wiley & Sons, Ltd.
Cicero TJ, Ellis MS, Paradis A, Ortbal Z.
Pharmacoepidemiol Drug Saf. 2010 Jul 1.
PURPOSE: Based on preclinical and clinical abuse liability assessments, fentanyl and other potent micro opioid agonists (e.g., hydromorphone and morphine) should be the most misused opioids if accessibility in the real world were not an issue. Since the latter is seldom true, we postulated that there would be a significant mismatch between actual and predicted rates of misuse. METHODS: We recruited 1818 prescription-opioid dependent patients entering drug treatment programs to complete an anonymous survey, covering drug use and health related issues. RESULTS: Hydrocodone and oxycodone products were the drugs of choice in 75% of patients, whereas potent micro opioid agonists (fentanyl, hydromorphone, and morphine), with the greatest predicted abuse potential, were very rarely chosen (<5% each). -
Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS)
Maier C, Baron R, Tölle TR, et al.
Pain. 2010 Sep;150(3):439-450.
Neuropathic pain is accompanied by both positive and negative sensory signs. To explore the spectrum of sensory abnormalities, 1236 patients with a clinical diagnosis of neuropathic pain were assessed by quantitative sensory testing (QST) following the protocol of DFNS (German Research Network on Neuropathic Pain), using both thermal and mechanical nociceptive as well as non-nociceptive stimuli. Data distributions showed a systematic shift to hyperalgesia for nociceptive, and to hypoesthesia for non-nociceptive parameters. Across all parameters, 92% of the patients presented at least one abnormality. Thermosensory or mechanical hypoesthesia (up to 41%) was more frequent than hypoalgesia (up to 18% for mechanical stimuli). Mechanical hyperalgesias occurred more often (blunt pressure: 36%, pinprick: 29%) than thermal hyperalgesias (cold: 19%, heat: 24%), dynamic mechanical allodynia (20%), paradoxical heat sensations (18%) or enhanced wind-up (13%). Hyperesthesia was less than 5%. Every single sensory abnormality occurred in each neurological syndrome, but with different frequencies: thermal and mechanical hyperalgesias were most frequent in complex regional pain syndrome and peripheral nerve injury, allodynia in postherpetic neuralgia. In postherpetic neuralgia and in central pain, subgroups showed either mechanical hyperalgesia or mechanical hypoalgesia. The most frequent combinations of gain and loss were mixed thermal/mechanical loss without hyperalgesia (central pain and polyneuropathy), mixed loss with mechanical hyperalgesia in peripheral neuropathies, mechanical hyperalgesia without any loss in trigeminal neuralgia. Thus, somatosensory profiles with different combinations of loss and gain are shared across the major neuropathic pain syndromes. The characterization of underlying mechanisms will be needed to make a mechanism-based classification feasible.
Maier C, Baron R, Tölle TR, et al.
Pain. 2010 Sep;150(3):439-450.
Neuropathic pain is accompanied by both positive and negative sensory signs. To explore the spectrum of sensory abnormalities, 1236 patients with a clinical diagnosis of neuropathic pain were assessed by quantitative sensory testing (QST) following the protocol of DFNS (German Research Network on Neuropathic Pain), using both thermal and mechanical nociceptive as well as non-nociceptive stimuli. Data distributions showed a systematic shift to hyperalgesia for nociceptive, and to hypoesthesia for non-nociceptive parameters. Across all parameters, 92% of the patients presented at least one abnormality. Thermosensory or mechanical hypoesthesia (up to 41%) was more frequent than hypoalgesia (up to 18% for mechanical stimuli).
