Pain
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Randomized Controlled Trial Multicenter Study
Alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist for the treatment of opioid-induced bowel dysfunction: results from a randomized, double-blind, placebo-controlled, dose-finding study in subjects taking opioids for chronic non-cancer pain.
Our objective was to investigate the efficacy and safety of alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist, in subjects with non-cancer pain and opioid-induced bowel dysfunction (OBD), and to identify at least one treatment regimen that improves OBD. Following a 2-week baseline period, 522 subjects reporting <3 spontaneous bowel movements (SBMs)/week (with >or=25% accompanied by a sensation of incomplete evacuation, straining, or lumpy hard stools), requiring analgesia equivalent to >or=30 mg oral morphine/day were randomized to alvimopan 0.5mg twice daily (BID), 1mg once daily (QD), 1mg BID, or placebo for 6 weeks. Compared with placebo, there was a statistically and clinically significant increase in mean weekly SBM frequency over the initial 3 weeks of treatment (primary endpoint) with alvimopan 0.5mg BID (+1.71 mean SBMs/week), alvimopan 1mg QD (+1.64) and alvimopan 1mg BID (+2.52); P<0.001 for all comparisons. ⋯ The alvimopan 0.5mg BID regimen demonstrated the best benefit-to-risk profile for managing OBD with alvimopan in this study population, with a side effect profile similar to that of placebo. There was no evidence of opioid analgesia antagonism. Competitive peripheral antagonism of opioids with alvimopan can restore GI function and relieve OBD without compromising analgesia.
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Multicenter Study
A patient-based national survey on postoperative pain management in France reveals significant achievements and persistent challenges.
We carried out a national survey on postoperative pain (POP) management in a representative sample (public/private, teaching/non-teaching, size) of 76 surgical centers in France. Based on medical records and questionnaires, we evaluated adult patients 24h after surgery, concerning information: pre and postoperative pain, evaluation, treatment and side effects. A local consultant provided information about POP management. ⋯ Epidural (1.5%) and peripheral (4.7%) nerve blocks were under used. Evaluation (63.4%) or treatment (74.1%) protocols were not available for all patients. This national, prospective, patient-based, survey reveals both progress and persistent challenges in POP management.
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Randomized Controlled Trial
Changes in morphine analgesia and side effects during daily subcutaneous administration in healthy volunteers.
Tolerance to the anti-nociceptive effects of opioids develops rapidly in animals. In contrast, humans with chronic pain show little or no loss of pain relief in prospective opioid trials of 4-8 weeks duration. Employing the Brief Thermal Sensitization model to induce transient cutaneous secondary hyperalgesia, we tested the hypothesis that opioid analgesic tolerance would develop rapidly. ⋯ During 4 days of twice-daily injections, the decline in anti-hyperalgesic effects of morphine did not reach statistical significance (p=0.06) compared to placebo. Morphine side effects did not correlate with anti-hyperalgesic effects and withdrawal symptoms did not emerge. As 4 days is the threshold for demonstrating analgesic tolerance to twice-daily morphine in animal models, a longer period of opioid exposure in healthy volunteers might be needed to detect analgesic tolerance.
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Spinal cord injury (SCI) results in deafferentation and the onset of neuropathic pain in a substantial proportion of people. Based on evidence suggesting motor cortex activation results in attenuation of neuropathic pain, we sought to determine whether neuropathic SCI pain could be modified by imagined movements of the foot. Fifteen subjects with a complete thoracic SCI (7 with below-level neuropathic pain and 8 without pain) were instructed in the use of movement imagery. ⋯ Two subjects without a history of pain or non-painful phantom sensations had onset of dysesthesia while performing imagined movements. This study reports exacerbation of pain in response to imagined movements and it contrasts with reports of pain reduction in people with peripheral neuropathic pain. The potential mechanisms underlying this sensory enhancement with movement imagery are discussed.
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This study examined within- and across-session consistency of visual analog scale (VAS) pain intensity and unpleasantness ratings of contact heat stimuli in 64 subjects (32 male). Subjects participated in four sessions over 14 days, with three stimulus series per session. Two levels of painful heat (pain-lo: rated 40, and pain-hi: rated 70 on a 0-100 VAS) were delivered in randomized order during each series, with temperatures selected on an individual subject basis to equalize pain perception across subjects. ⋯ Across- and within-session CVs were significantly negatively correlated with individual ratings of the stimuli, but were not correlated with demographic or psychosocial factors. Furthermore, sex did not impact consistency of ratings, demonstrating that neither sex is more variable in ratings than the other over time. Taken together, these findings suggest that VAS ratings of painful contact heat are relatively stable over time but the variability of these ratings is significantly impacted by the perceived intensity of the stimulus.