Pain
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Randomized Controlled Trial Clinical Trial
Phase III evaluation of nortriptyline for alleviation of symptoms of cis-platinum-induced peripheral neuropathy.
Tricyclic antidepressants have been reported to relieve the paresthesiae associated with peripheral neuropathies of many etiologies. We designed a randomized, double-blind, placebo-controlled, crossover trial to establish the efficacy of nortriptyline in the treatment of cis-diamminedichloroplatinum (CDDP)-induced paresthesiae. The study included 51 evaluable patients with CDDP-induced peripheral neuropathy and painful paresthesiae. ⋯ In summary, nortriptyline failed to demonstrate strong evidence of any effect on paresthesia or pain. The presence of a potential effect which appeared in the second period of the crossover design is questionable due to the observed carryover effect. Cross-validation sensitivity analysis of results support the conclusion that nortriptyline provides modest improvement at best over placebo in terms of chemotherapy-related neuropathy.
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Little research has examined the role of patient cognitive and behavioral responses, including catastrophizing, in adjustment to chronic pain associated with spinal cord injury (SCI). The objective of this study was to examine the associations of catastrophizing and specific pain coping strategies with pain intensity, psychological distress, and pain-related disability among individuals with chronic pain and SCI, after controlling for important demographic and SCI-related variables that might affect outcomes. Participants in this study were 174 community residents with SCI and chronic pain who completed a mailed questionnaire that included the SF-36 Mental Health scale, Coping Strategies Questionnaire, and Graded Chronic Pain Scale. ⋯ The coping and catastrophizing scales accounted for an additional 30% of the variance in psychological distress (P<0.001) and 11% of the variance in pain-related disability (P<0.001), after controlling for pain intensity and demographic and SCI variables. Catastrophizing, but not any other single pain coping strategy, was consistently strongly and independently associated with the outcome measures. Potentially, the assessment and treatment of catastrophizing may reduce psychological distress and pain-related disability among individuals with chronic pain and SCI.
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Although activation of alpha(2)-adrenoceptors is known to play an important role in mediating antinociception, the contribution of various alpha(2)-adrenoceptor subtypes in modulating trigeminal nociception remains unknown since subtype specific agonists and antagonists are not available. The present study investigated the functional role of alpha(2)-adrenoceptor subtypes in modulating the N-methyl-D-aspartate-induced nociceptive behavior in the medullary dorsal horn by using antisense oligodeoxynucleotides to selectively knock-down the receptor subtypes. Microinjection of N-methyl-D-aspartate (2 nmol in 10 microl) through a cannula implanted dorsal to the medullary dorsal horn produced a total of 164.9+/-8.8 scratches in the facial region (n=14), and the scratching behavior lasted for 77.8+/-5.2s (n=14). ⋯ Antisense treatment reduced alpha(2A) and alpha(2C) receptor immunoreactivity in the medullary dorsal horn compared to the sense and the vehicle-treated animals. Quantitative image analysis revealed a significant decrease in pixel intensity following the antisense treatment. These results indicate that activation of alpha(2A) adrenoceptor plays an important role in mediating the antinociceptive effect of clonidine in the medullary dorsal horn in the rat.
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Microelectrode recordings of impulse activity in nociceptive C fibres were performed in cutaneous fascicles of the peroneal nerve at the knee level in healthy human subjects. Mechano-heat responsive C units (CMH), mechano-insensitive but heat-responsive (CH) as well as mechano-insensitive and heat-insensitive C units (CM(i)H(i)) were identified. A subgroup of the mechano-insensitive units was readily activated by histamine. ⋯ In conclusion, we have shown that ATP injections at high concentrations activate C-nociceptors in healthy human skin, without preference for mechano-responsive or mechano-insensitive units. ATP did not sensitise human C fibres for mechanical or heat stimuli. We discuss how various mechanisms might contribute to the observed responses to ATP.
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Recent studies indicate that sustained opioid administration produces increased expression of spinal dynorphin, which promotes enhanced sensitivity to non-noxious and noxious stimuli. Such increased "pain" may manifest behaviorally as a decrease in spinal antinociceptive potency. Here, the possibility of similar mechanisms in the antinociception of spinal cannabinoids was explored. ⋯ Daily MK-801 pretreatments, prior to WIN 55,212-2 injection, also produced a significant block of antinociceptive tolerance. These data suggest that like opioids, repeated spinal administration of a cannabinoid CB1 agonist elicits abnormal pain, which results in increased expression of spinal dynorphin. Manipulations that block cannabinoid-induced pain also block the behavioral manifestation of cannabinoid tolerance.