The journal of pain : official journal of the American Pain Society
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Randomized Controlled Trial
Efficacy of Inhaled Cannabis on Painful Diabetic Neuropathy.
A randomized, double-blinded, placebo controlled crossover study was conducted in 16 patients with painful diabetic peripheral neuropathy to assess the short-term efficacy and tolerability of inhaled cannabis. In a crossover design, each participant was exposed to 4 single dosing sessions of placebo or to low (1% tetrahydrocannabinol [THC]), medium (4% THC), or high (7% THC) doses of cannabis. Baseline spontaneous pain, evoked pain, and cognitive testing were performed. Subjects were then administered aerosolized cannabis or placebo and the pain intensity and subjective "highness" score was measured at 5, 15, 30, 45, and 60 minutes and then every 30 minutes for an additional 3 hours. Cognitive testing was performed at 5 and 30 minutes and then every 30 minutes for an additional 3 hours. The primary analysis compared differences in spontaneous pain over time between doses using linear mixed effects models. There was a significant difference in spontaneous pain scores between doses (P < .001). Specific significant comparisons were placebo versus low, medium, and high doses (P = .031, .04, and <.001, respectively) and high versus low and medium doses (both P < .001). There was a significant effect of the high dose on foam brush and von Frey evoked pain (both P < .001). There was a significant negative effect (impaired performance) of the high dose on 2 of the 3 neuropsychological tests (Paced Auditory Serial Addition Test, Trail Making Test Part B. ⋯ This small, short-term, placebo-controlled trial of inhaled cannabis demonstrated a dose-dependent reduction in diabetic peripheral neuropathy pain in patients with treatment-refractory pain. This adds preliminary evidence to support further research on the efficacy of the cannabinoids in neuropathic pain.
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The study explored the analgesic effects of transcranial direct current stimulation (tDCS) over the motor cortex on postamputation phantom limb pain (PLP). Eight subjects with unilateral lower or upper limb amputation and chronic PLP were enrolled in a crossover, double-blind, sham-controlled treatment program. For 5 consecutive days, anodal (active or sham) tDCS was applied over the motor cortex for 15 minutes at an intensity of 1.5 mA. The 5-day treatment with active, but not sham, tDCS induced a sustained decrease in background PLP and in the frequency of PLP paroxysms, which lasted for 1 week after the end of treatment. Moreover, on each day of active tDCS, patients reported an immediate PLP relief, along with an increased ability to move their phantom limb. Patients' immediate responses to sham tDCS, on the contrary, were variable, marked by an increase or decrease of PLP levels from baseline. These results show that a 5-day treatment of motor cortex stimulation with tDCS can induce stable relief from PLP in amputees. Neuromodulation targeting the motor cortex appears to be a promising option for the management of this debilitating neuropathic pain condition, which is often refractory to classic pharmacologic and surgical treatments. ⋯ The study describes sustained and immediate effects of motor cortex stimulation by tDCS on postamputation PLP, whose analgesic action seems linked to the motor reactivation of the phantom limb. These results are helpful for the exploitation of tDCS as a therapeutic tool for the management of neuropathic pain.
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Although nonnoxious, high-frequency electrical stimulation applied segmentally (ie, conventional transcutaneous electrical nerve stimulation [TENS]) has been proposed to modulate pain, the mechanisms underlying analgesia remain poorly understood. To further elucidate how TENS modulates pain, we examined evoked responses to noxious thermal stimuli after the induction of sensitization using capsaicin in healthy volunteers. We hypothesized that sensitization caused by capsaicin application would unmask TENS analgesia, which could not be detected in the absence of sensitization. Forty-nine healthy subjects took part in a series of experiments. The experiments comprised the application of topical capsaicin (.075%) on the left hand in the C6 dermatome, varying the location of TENS (segmental, left C6 dermatome, vs extrasegmental, right shoulder), and assessing rating of perception (numeric rating scale: 0-10) and evoked potentials to noxious contact heat stimuli. The extrasegmental site was included as a control condition because previous studies indicate no analgesic effect to remote conventional TENS. Conventional TENS had no significant effect on rating or sensory evoked potentials in subjects untreated with capsaicin. However, segmental TENS applied in conjunction with capsaicin significantly reduced sensation to noxious thermal stimuli following a 60-minute period of sensitization. ⋯ The study indicates that sensitization with capsaicin unmasks the analgesic effect of conventional TENS on perception of noxious contact heat stimuli. Our findings indicate that TENS may be interacting segmentally to modulate distinct aspects of sensitization, which in turn results in analgesia to thermal stimulation.
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Injury- or disease-induced artemin (ARTN) signaling can sensitize primary afferents and contribute to persistent pain. We demonstrate that administration of an ARTN neutralizing antibody, anti-artemin (α-ARTN), can block the development of, and reverse already established, bladder hyperalgesia associated with cyclophosphamide-induced cystitis in mice. We further demonstrate that α-ARTN therapy blocks upregulation of TRPA1, an ion channel contributing to persistent bladder pain during cyclophosphamide-induced cystitis, and decreases phospho-ERK1/2 immunoreactivity in regions of the spinal cord receiving bladder afferent input. Thus, α-ARTN is a promising novel therapeutic approach for treatment of bladder hyperalgesia that may be associated with interstitial cystitis/painful bladder syndrome, as well as cystitis associated with antitumor or immunosuppressive cyclophosphamide therapy. ⋯ α-ARTN therapy effectively prevented and reversed ongoing bladder hyperalgesia in an animal model of cystitis, indicating its potential as an efficacious treatment strategy for ongoing bladder pain associated with interstitial cystitis/painful bladder syndrome.
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Randomized Controlled Trial Multicenter Study
The Contribution of Differential Opioid Responsiveness to Identification of Opioid Risk in Chronic Pain Patients.
The Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R) predicts increased risk of opioid misuse in chronic pain patients. We evaluated whether higher SOAPP-R scores are associated with greater opioid reinforcing properties, potentially contributing to their predictive utility. Across 2 counterbalanced laboratory sessions, 55 chronic low back pain sufferers completed the SOAPP-R at baseline and measures of back pain intensity, evoked pain responsiveness (thermal, ischemic), and subjective opioid effects after receiving intravenous morphine (.08 mg/kg) or saline placebo. Morphine effect measures were derived for all outcomes, reflecting the difference between morphine and placebo condition values. Higher SOAPP-R scores were significantly associated with greater desire to take morphine again, less feeling down and feeling bad, and greater reductions in sensory low back pain intensity following morphine administration. This latter effect was due primarily to SOAPP-R content assessing medication-specific attitudes and behavior. Individuals exceeding the clinical cutoff (18 or higher) on the SOAPP-R exhibited significantly greater morphine liking, desire to take morphine again, and feeling sedated; less feeling bad; and greater reductions in sensory low back pain following morphine. The SOAPP-R may predict elevated opioid risk in part by tapping into individual differences in opioid reinforcing effects. ⋯ Based on placebo-controlled morphine responses, associations were observed between higher scores on a common opioid risk screener (SOAPP-R) and greater desire to take morphine again, fewer negative subjective morphine effects, and greater analgesia. Opioids may provide the best analgesia in those patients at greatest risk of opioid misuse.