Pain
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Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices, rather than using discontinuous events--such as number or proportion of patients with 50% pain relief. Because mean data inadequately describe information with a non-normal distribution, combining mean data in systematic reviews may compromise the results. Showing that dichotomous data can reliably be derived from mean data, at least in acute pain models, indicates that more meaningful overviews or meta-analysis may be possible. ⋯ Mean %maxTOTPAR correlated with the proportion of patients with > 50%maxTOTPAR (r2 = 0.90). The relationship calculated from all the 45 treatments predicted to within three patients the number of patients with more than 50% pain relief in 42 of 45 treatments, and 98.8% of 10,000 simulated treatments. For seven effective treatments, actual numbers-needed-to-treat (NNT) to achieve > 50%maxTOTPAR compared with placebo were very similar to those derived from calculated data.
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Pain experienced in a limb prior to amputation may influence the course of phantom limb pain many months later. Katz and Melzack (1990) found that 42% of their sample reported a 'somatosensory pain memory' which resembled the quality and location of a painful, or non-painful pre-amputation sensation. For many amputees, pain memories are vivid experiences which incorporate both emotional and sensory aspects of the pre-amputation pain (Katz 1992). ⋯ The present case study used a diary design to examine whether 'triggers' could be identified for somatosensory pain memories. Over a 9-month period, the patient reported daily experience of ongoing phantom limb pain, generally confined to the distal part of the limb, and 5 episodes of injury-related phantom limb pain, primarily experienced in the calf of the missing limb. A 'trigger' was identified for each of the episodes of injury-related phantom limb pain, and a significant finding in this study was that two episodes of injury-related phantom limb pain were associated with cognitive and/or emotional, rather than sensory 'triggers'.
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Behavioral and electrophysiological methods were used to investigate the hyperalgesia and allodynia, and functional changes in lumbar spinal dorsal horn neurons, in a model of neuropathic pain (Selzer et al. 1990) involving ligation of one-third to one-half of one sciatic nerve in rats. One and 5 weeks following ligation, there was a significant reduction in hind limb withdrawal latency to noxious radiant heat on the operated side and, to a lesser degree, on the unoperated side. By 16 weeks, heat withdrawal latencies were reduced about equally (approximately 40%) on both sides. ⋯ Mechanical receptive field areas were not significantly different between ipsi- and contralateral sides in the sham and 5-week post-ligation groups, or between sham and 5-week post-ligation groups. However, receptive field areas were significantly larger in the 16-week post-ligation group (both ipsi- and contralateral to ligation) compared to sham and 5-week post-ligation groups. The results suggest that allodynia may be associated with a chronic enhancement of neuronal mechanosensitivity, but that the thermal hyperalgesia is not associated with enhanced neuronal responsiveness or force of withdrawal.
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We have examined the interactions between NMDA receptors and opioid effects in isolated neonatal rat spinal cord. Electrical stimulation of a lumbar dorsal root evoked a nociceptive-related slow ventral root potential (sVRP) recorded at the corresponding ipsilateral ventral root. The kappa opiate receptor agonist U69,593 (2.5 nM-1 microM) depressed sVRP area by a maximum of 80%, EC50 was approximately 33 nM. ⋯ MK-801 co-applied with morphine blocked the rebound increase in sVRP area following naloxone. These results suggest that (1) both mu and kappa receptor agonists exert similar selective depressant effects on spinal nociceptive neurotransmission; (2) mu but not kappa agonists exert prolonged excitatory effects that oppose the depression; and (3) NMDA receptors play a role in determining opioid analgesic potency and naloxone-precipitated hyperresponsiveness. The results may be related to initial steps in the development of acute tolerance to mu opioids, and suggest that tolerance to kappa opioids may have a different mechanism.
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Randomized Controlled Trial Comparative Study Clinical Trial
Rectal afferent function in patients with inflammatory and functional intestinal disorders.
Chronic symptoms of abdominal pain and discomfort are reported by patients with inflammatory bowel disease (IBD) and functional disorders of the gut, such as Irritable Bowel Syndrome (IBS). It has recently been suggested that transient inflammatory mucosal events may result in long-lasting sensitization of visceral afferent pathways. To determine the effect of recurring intestinal tissue irritation on lumbosacral afferent pathways, and to identify a plausible mechanism that could account for the overlap in symptomatology between IBD and IBS, we compared rectal afferent mechanisms in patients with Crohn's disease (inflammation limited to the ileum) with those observed in patients with diarrhea-predominant IBS. ⋯ These findings demonstrate that chronic ileal inflammation is associated with increased thresholds for discomfort and greatly diminished systemic autonomic reflex responses. In contrast, IBS patients show lowered thresholds for discomfort associated with increased autonomic responses. The findings in Crohn's patients may result from descending bulbospinal inhibition of sacral dorsal horn neurons in response to chronic intestinal tissue irritation.