The journal of pain : official journal of the American Pain Society
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Two lines of evidence about the association between the experience of pain and brain state (measured via electroencephalogram or EEG) have recently come to light. First, research from a number of sources suggests a link between brain EEG activity and the experience of pain. Specifically, this research suggests that the subjective experience of pain is associated with relatively lower amplitudes of slower wave (delta, theta, and alpha) activity and relatively higher amplitudes of faster wave (beta) activity. Second, there has been a recent increase in interest in interventions that impact the cortical neuromodulation of pain, including behavioral treatments (such as self-hypnosis training and neurofeedback) and both invasive and noninvasive brain stimulation. Although a direct causal link between experience of pain and brain activity as measured by EEG has not been established, the targeting of pain treatment at a cortical level by trying to affect EEG rhythms directly is an intriguing possibility. ⋯ Preliminary evidence suggests the possibility, which has not yet adequately tested or proven, that the experience of chronic pain is linked to cortical activity as assessed via an electroencephalogram. Support for this hypothesis would have important implications for understanding the mechanisms that underlie a number of pain treatments, and for developing new innovative treatments for chronic pain management.
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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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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.