The journal of pain : official journal of the American Pain Society
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Randomized Controlled Trial
Low-dose vaporized cannabis significantly improves neuropathic pain.
We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling medium-dose (3.53%), low-dose (1.29%), or placebo cannabis with the primary outcome being visual analog scale pain intensity. Psychoactive side effects and neuropsychological performance were also evaluated. Mixed-effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the 2 active dose groups' results (P > .7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo versus low-dose, 2.9 for placebo versus medium-dose, and 25 for medium- versus low-dose. As these NNTs are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well tolerated, and neuropsychological effects were of limited duration and readily reversible within 1 to 2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. ⋯ The analgesia obtained from a low dose of delta-9-tetrahydrocannabinol (1.29%) in patients, most of whom were experiencing neuropathic pain despite conventional treatments, is a clinically significant outcome. In general, the effect sizes on cognitive testing were consistent with this minimal dose. As a result, one might not anticipate a significant impact on daily functioning.
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Comparative Study
Comparison of opioid doctor shopping for tapentadol and oxycodone: a cohort study.
Obtaining opioids from multiple prescribers, known as doctor shopping, is 1 example of opioid abuse and diversion. The dual mechanism of action of tapentadol could make tapentadol less likely to be abused than other opioids. The aim of this retrospective cohort study was to compare the risk of shopping behavior between tapentadol immediate release (IR) and oxycodone IR. Subjects exposed to tapentadol or oxycodone with no recent opioid use were included and followed for 1 year. The primary outcome was the proportion of subjects who developed shopping behavior defined as subjects who had opioid prescriptions written by >1 prescriber with ≥1 day of overlap filled at ≥3 pharmacies. The opioids involved in the shopping episodes were assessed. A total of 112,821 subjects were exposed to oxycodone and 42,940 to tapentadol. Shopping behavior was seen in .8% of the subjects in the oxycodone group and in .2% of the subjects in the tapentadol group, for an adjusted odds ratio of 3.5 (95% confidence interval, 2.8 to 4.4). In the oxycodone group, 28.0% of the shopping events involved exclusively oxycodone, whereas in the tapentadol group, .6% of the shopping events involved exclusively tapentadol. Results suggest that the risk of shopping behavior is substantially lower with tapentadol than with oxycodone. ⋯ The risk of opioid doctor shopping, ie, obtaining opioid prescriptions from multiple prescribers, is lower with tapentadol than with oxycodone.
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Randomized Controlled Trial
Expectations modulate heterotopic noxious counter-stimulation analgesia.
The present study examined the contribution of expectations to analgesia induced by heterotopic noxious counter-stimulation (HNCS) in healthy volunteers assigned to a control group or 1 of 3 experimental groups in which expectations were either assessed (a priori expectations) or manipulated using suggestions (hyperalgesia and analgesia). Acute shock-pain, the nociceptive flexion reflex (RIII-reflex), and shock-related anxiety were measured in response to electrical stimulations of the right sural nerve in the baseline, HNCS, and recovery periods. Counter-stimulation was applied on the contralateral forearm using a flexible cold pack. A priori expectations were strongly associated with the actual magnitude of the analgesia induced by HNCS. In comparison to the control condition, suggestions of hyperalgesia led to an increase in RIII-reflex amplitude and shock-pain, while suggestions of analgesia resulted in a greater decrease in RIII-reflex amplitude, which confirms that the analgesic process normally activated by HNCS can be blocked or enhanced by the verbal induction of expectations through suggestions. Changes in shock-anxiety induced by these suggestions were correlated to changes in shock-pain and RIII-reflex, but these changes did not emerge as a mediator of the association between manipulated expectations and HNCS analgesia. Overall, the results demonstrate that HNCS analgesia is modulated by expectations, either from a priori beliefs or suggestions, and this appears to be independent of anxiety processes. ⋯ This study demonstrates that a priori and manipulated expectations can enhance or block HNSC analgesia. Results also suggest that expectations might influence responses to analgesic treatments by altering descending modulation and contribute to observed deficit in pain inhibition processes of chronic pain patients.
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Fear of injury has been posited as crucial in pain-related anxiety and in the development of chronic pain; however, research has only measured fear of injury indirectly through other constructs (eg, fear of illness and fear of movement). The current study tested fear of injury as an independent contributor to pain-related anxiety and impairment. Patients (n = 78; 37% women) in a work-hardening treatment program for chronic low back pain completed self-report measures of pain-related anxiety, anxiety sensitivity, fear of injury, current pain, and impairment. Behavioral measures of impairment included lifting capacity, treatment outcomes, and days absent from treatment. Structural equation modeling tested the role of fear of injury within contemporary theory. Fit for the theoretical model was excellent and superior to an alternative model. Variance accounted for in pain-related anxiety by fear of injury, anxiety sensitivity, and current pain was 64%, while pain-related anxiety and current pain predicted 49% of variance in latent impairment. Fear of injury directly predicted pain-related anxiety (β = .42) and indirectly predicted impairment through pain-related anxiety (β = .19). Fear of injury may warrant theoretical and clinical consideration as an important contributor to pain-related anxiety and impairment; however, research is needed to explore how it may be causally related with other constructs. ⋯ Fear of injury directly predicts pain-related anxiety and indirectly predicts self-reported and behavioral impairment. Fear of injury may warrant inclusion in contemporary theories of chronic pain. Clinicians may benefit from considering the construct in interventions for chronic pain.
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Spinal glial cells contribute to the development of many types of inflammatory and neuropathic pain. Here the contribution of spinal astrocytes and astrocyte gap junctions to oxaliplatin-induced mechanical hypersensitivity was explored. The expression of glial fibrillary acidic protein (GFAP) in spinal dorsal horn was significantly increased at day 7 but recovered at day 14 after oxaliplatin treatment, suggesting a transient activation of spinal astrocytes by chemotherapy. Astrocyte-specific gap junction protein connexin 43 (Cx43) was significantly increased in dorsal horn at both day 7 and day 14 following chemotherapy, but neuronal (connexin 36 [Cx36]) and oligodendrocyte (connexin 32 [Cx32]) gap junction proteins did not show any change. Blockade of astrocyte gap junction with carbenoxolone (CBX) prevented oxaliplatin-induced mechanical hypersensitivity in a dose-dependent manner and the increase of spinal GFAP expression, but had no effect once the mechanical hypersensitivity induced by oxaliplatin had fully developed. These results suggest that oxaliplatin chemotherapy induces the activation of spinal astrocytes and this is accompanied by increased expression of astrocyte-astrocyte gap junction connections via Cx43. These alterations in spinal astrocytes appear to contribute to the induction but not the maintenance of oxaliplatin-induced mechanical hypersensitivity. Combined, these results suggest that targeting spinal astrocyte/astrocyte-specific gap junction could be a new therapeutic strategy to prevent oxaliplatin-induced neuropathy. ⋯ Spinal astrocytes but not microglia were recently shown to be recruited in paclitaxel-related chemoneuropathy. Here, spinal astrocyte gap junctions are shown to play an important role in the induction of oxaliplatin neuropathy.