The journal of pain : official journal of the American Pain Society
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Repeated daily application of transcutaneous electrical nerve stimulation (TENS) results in tolerance, at spinal opioid receptors, to the antihyperalgesia produced by TENS. Since N-methyl-D-aspartate (NMDA) receptor antagonists prevent analgesic tolerance to opioid agonists, we hypothesized that blockade of NMDA receptors will prevent tolerance to TENS. In rats with knee joint inflammation, TENS was applied for 20 minutes daily at high-frequency (100 Hz), low-frequency (4 Hz), or sham TENS. Rats were treated with the NMDA antagonist MK-801 (0.01 mg/kg to 0.1 mg/kg) or vehicle daily before TENS. Paw withdrawal thresholds were tested before and after inflammation and before and after TENS treatment for 4 days. On day 1, TENS reversed the decreased mechanical withdrawal threshold induced by joint inflammation. On day 4, TENS had no effect on the decreased withdrawal threshold in the group treated with vehicle, demonstrating development of tolerance. However, in the group treated with 0.1 mg/kg MK-801, TENS significantly reversed the mechanical withdrawal thresholds on day 4, demonstrating that tolerance did not develop. Vehicle-treated animals developed cross-tolerance at spinal opioid receptors. Treatment with MK-801 reversed this cross-tolerance at spinal opioid receptors. In summary, blockade of NMDA receptors prevents analgesic tolerance to daily TENS by preventing tolerance at spinal opioid receptors. ⋯ Observed tolerance to the clinical treatment of TENS could be prevented by administration of pharmaceutical agents with NMDA receptors activity such as ketamine or dextromethorphan.
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The objective of the present study was to evaluate the time course of changes in peripheral nerve insulin receptor (IR) signaling and compare observed findings with behavioral responses to noxious mechanical and thermal stimuli in streptozotocin (STZ)-diabetic rats over 12 weeks of diabetes. Diabetic rats developed mechanical hyperalgesia, as indicated by decreased paw withdrawal thresholds to mechanical stimuli that were detectable after 2 weeks of diabetes; they also developed thermal hypoalgesia, as indicated by increased tail flick latencies to thermal stimuli that were detectable at 1 week of diabetes. Western blot analysis revealed decreased phosphorylated: total IR protein ratio that was detectable as early as 2 weeks of diabetes, whereas phosphorylated:total Akt protein ratio was decreased at 2 weeks and increased at 12 weeks of diabetes with unchanged PI-3K protein levels. To our knowledge, the present study is the first to demonstrate that impaired peripheral nerve IR signaling, as indicated by decreased phosphorylated:total IR protein ratio, coincides with early mechanical hyperalgesia and thermal hypoalgesia in STZ-diabetic rats. This finding may improve understanding of how altered pain sensation develops rapidly in this model. ⋯ This study examined peripheral nerve IR signaling during the early course of altered nociception in STZ-diabetic rats. In diabetic rats, impaired peripheral nerve IR signaling is observed shortly after STZ injection, as is altered nociception. This finding suggests a possible role of impaired IR signaling in diabetic sensory neuropathy.
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Women have a higher prevalence of fibromyalgia and myofascial pain than men, but sex differences in muscle pain are inconsistently detected. We examined sex differences in ratings and effects of recalled and experimentally-induced muscle pain. In study 1 (n = 188), participants completed a questionnaire about recalled muscle pain. In study 2 (n = 55), participants described muscle pain from an exercise stimulus across 3 days by telephone. Muscle pain ratings, self-care behaviors for muscle pain, and effects of muscle pain on activities were measured. No significant sex differences were found except that women tended to view exercise as more effective for decreasing muscle pain than men (F (1, 187) = 5.43, P = .02, eta(2) = .03), fewer women performed exercise for induced muscle pain than men, and women's activity interference was significantly higher than men's at the third day after exercise (F (2, 42) = 6.54, P = .01, eta(2) = .14). These findings support the absence of meaningful sex differences in muscle pain ratings. However, additional investigations are needed that consider the daily activities completed by people and the prevalence and incidence of performing a wide range of self-care behaviors for pain. ⋯ These studies support that sex differences are not present in recalled and experimentally-induced muscle pain ratings. Therefore, we must be cautious about generalizing the musculoskeletal pain literature to muscle pain. Additional research is needed to interpret potential sex differences in self-care behaviors for muscle pain and activity interference from muscle pain.
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Visceral injury has been shown to alter somatic sensitivity, but little is known about the effect of somatic insult on the viscera. In the present study, we examined (1) the effect of colon inflammation on somatic sensitivity and (2) the affect of hind paw incision on colon sensitivity. After intracolonic administration of trinitrobenzene sulfonic acid (TNBS) or zymosan, visceromotor responses to colorectal distension were increased to post-treatment day 8. Mechanical withdrawal thresholds in the hind paw were decreased in TNBS- and in zymosan-treated rats until post-intracolonic treatment day 2. There was no change in hind paw heat withdrawal latency in either group. Plantar incision of the hind paw resulted in a decrease in both hind paw mechanical withdrawal threshold and heat withdrawal latency and significantly increased the visceromotor response to colorectal distension from postincision days 1 to 8. The colon hypersensitivity was of longer duration than hyperalgesia at the site of hind paw incision. These results support the hypothesis that somatic injury and visceral inflammation can alter central processing of visceral and somatic inputs, respectively. ⋯ Surgical procedures are common and typically associated with hyperalgesia at and around the site of incision. This report establishes in a model of postsurgical pain and hyperalgesia that a long-lasting visceral hypersensitivity may also accompany postsurgical hyperalgesia.