Pain
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We investigated the effects of acute and of chronic morphine treatment on T-lymphocyte function and natural killer (NK) cell activity in rats receiving chronic constriction injury (CCI) of the sciatic nerve. T-Lymphocyte function was evaluated based on concanavalin-A (ConA)- and phytohemagglutinin (PHA)-induced splenocyte proliferation. The effects of morphine on thermal hyperalgesia were also assessed by measuring paw withdrawal latency (PWL) in rats. ⋯ No tolerance to the suppression of NK cell activity and splenocyte proliferation was observed after chronic morphine treatment. These data suggest that both acute and chronic morphine treatment can cause a dose-dependent reversal of thermal hyperalgesia and inhibition of NK cell activity and splenocyte proliferation in rats with sciatic CCI, without concomitant development of tolerance. Opioid therapy for chronic neuropathic pain should be used cautiously, especially in immune-compromised cases.
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The hypothesis that the pain and allodynia associated with post-herpetic neuralgia (PHN) is maintained by a combination of input from preserved primary afferent nociceptors and sensitization of central pain transmitting neurons was examined in 17 subjects with PHN. Pain, allodynia, thermal sensory function, cutaneous innervation, and response to controlled application of 0.075% capsaicin were measured. ⋯ In three of the 'capsaicin responders' the area of allodynia expanded into previously non-allodynic and non-painful skin that had normal sensory function and cutaneous innervation. These observations support the hypothesis that allodynia in some PHN patients is a form of chronic secondary hyperalgesia maintained by input from intact and possibly 'irritable' primary afferent nociceptors to a sensitized CNS.
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Clinical Trial Controlled Clinical Trial
Effect of tonic muscle pain on short-latency jaw-stretch reflexes in humans.
The modulation of human jaw-stretch reflexes by experimental muscle pain was studied in three experiments. Short-latency reflex responses were evoked in the masseter and temporalis muscles by fast stretches (1 mm displacement, 10 ms ramp time) before, during and 15 min after a period with tonic pain. In Expt. ⋯ These results indicate that experimental jaw-muscle pain facilitates the short-latency (8-9 ms), probably monosynaptic, jaw-stretch reflex as revealed by both sEMG and imEMG. This effect could not be accounted for by variability in pre-stimulus EMG activity. An increased sensitivity of the fusimotor system at this level of static muscle excitation is suggested as a possible mechanism, which could contribute to an increased stiffness of the jaw-muscles during pain.
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Clinical Trial
Intradermal injection of norepinephrine evokes pain in patients with sympathetically maintained pain.
Tissue injuries, with or without involvement of nerves, may lead to ongoing pain and hyperalgesia to external stimuli. In a subset of patients, the pain is maintained by sympathetic efferent activity (SMP). We investigated if the peripheral administration of the alpha-adrenergic agonist, norepinephrine (NE), in physiologically relevant doses resulted in pain in patients with SMP. ⋯ Two of the three patients who did not receive pain relief following phentolamine infusion also did not report pain to the NE injections. We conclude that NE injections produce pain in SMP patients at doses that are at the threshold for producing vasoconstriction. These studies support a role for cutaneous adrenoceptors in the mechanisms of sympathetically maintained pain.
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The ability of pindolol, a beta-adrenoceptor blocker/5-hydroxytryptamine(1A/1B) antagonist, to enhance the clinical antidepressant response to selective serotonin re-uptake inhibitors is generally attributed to a blocking of the feedback that inhibits the serotoninergic neuronal activity mediated by somatodendritic 5-hydroxytryptamine (5-HT)(1A) autoreceptors. The current study examined the ability of pindolol to enhance the analgesic effect of tramadol, an atypical centrally-acting analgesic agent with relatively weak opioid receptor affinity and which, like some antidepressants, is able to inhibit the re-uptake of 5-HT in the raphe nuclei. ⋯ Moreover, (+/-)8-OH-DPAT (0.125-1 mg/kg, s.c.), a selective 5-HT(1A) agonist, reduces the analgesic effect of tramadol in the same tests. These results suggest an implication of the somatodendritic 5-HT(1A) receptors in the analgesic effect of tramadol and open a new adjuvant analgesic strategy for the use of this compound.