Articles: hyperalgesia.
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Aliment. Pharmacol. Ther. · Feb 2007
Randomized Controlled TrialNeurokinin-1 receptor antagonism in a human model of visceral hypersensitivity.
Substance P acting via the neurokinin-1 receptor is involved in the development of hyperalgesia, although studies using neurokinin-1 receptor antagonists (NK-1RA) in human somatic pain have been disappointing. ⋯ The lack of effect of NK-1RA on oesophageal pain threshold in our model does not support a role for Substance P in the development of acid-induced oesophageal allodynia.
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Sympathetically maintained pain could either be mediated by ephaptic interactions between sympathetic efferent and afferent nociceptive fibers or by catecholamine-induced activation of nociceptive nerve endings. We report here single fiber recordings from C nociceptors in a patient with sympathetically maintained pain, in whom sympathetic blockade had repeatedly eliminated the ongoing pain in both legs. We classified eight C-fibers as mechano-responsive and six as mechano-insensitive nociceptors according to their mechanical responsiveness and activity-dependent slowing of conduction velocity (latency increase of 0.5+/-1.1 vs. 7.1+/-2.0 ms for 20 pulses at 0.125 Hz). ⋯ Moreover, their activity-dependent slowing was typical for mechano-insensitive nociceptors. We conclude that sensitized mechano-insensitive nociceptors can be activated by endogenously released catecholamines and thereby may contribute to sympathetically maintained pain. No evidence for ephaptic interaction between sympathetic efferent and nociceptive afferent fibers was found.
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Clinical Trial
Clarification of developing and established clinical allodynia and pain-free outcomes.
The aim of this study was to determine whether clinical indicators of cutaneous allodynia predict the success of migraine therapy with sumatriptan using a brief questionnaire. ⋯ Headaches without allodynia were aborted when treated early or late, and headaches with allodynia were aborted only when allodynia was not present after treatment. These findings suggest that different mechanisms account for allodynia before and after treatment; a developing phase in which central sensitization depends on incoming pain signals from the peripheral nociceptors and an established phase in which the sensitization becomes independent of the pain signals that come from the dura.
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It is not known if a cytokine cascade develops during muscle inflammation and whether cytokines contribute to muscle inflammatory pain. We measured plasma and tissue cytokine concentrations, and behavioral responses to noxious mechanical stimuli, after inducing inflammation in the gastrocnemius muscle and the hind paw of rats. Tissue and plasma samples were taken 3, 6, or 24 h after carrageenan or saline injection into one of the 2 sites. Tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and cytokine-induced neutrophil chemoattractant 1 (CINC-1) concentrations were measured. Hyperalgesia was present 3 h after carrageenan injection into the hind paw and muscle. The TNF-alpha was elevated significantly in the inflamed hind paw tissue (P < .001) but not in inflamed muscle tissue. IL-1beta was elevated 6 h after carrageenan injection in the hind paw tissue but only 24 h in the muscle tissue (P < .001). The IL-6 was elevated 3 h after injection in the hind paw tissue but only after 6 h in the muscle tissue (P < .01). The CINC-1 in plasma, muscle, and hind paw was elevated from 3 h to 24 h after carrageenan injection (P < .01). The release of IL-1beta and IL-6, known to mediate hyperalgesia elsewhere, is delayed in muscle inflammation compared with cutaneous inflammation, whereas TNF-alpha is not elevated during muscle inflammation. ⋯ The quality and mechanisms of muscle pain are different from that of cutaneous pain. So too is the pattern of cytokine release during inflammation. Inhibiting TNF-alpha is unlikely to be effective in managing inflammatory muscle pain, but other cytokines, notably IL-1beta and CINC-1, may prove useful therapeutic targets.
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Fundam Clin Pharmacol · Feb 2007
Effect of resveratrol, a polyphenolic phytoalexin, on thermal hyperalgesia in a mouse model of diabetic neuropathic pain.
Diabetic neuropathic pain, an important microvascular complication in diabetes mellitus, has been recognized as one of the most difficult types of pain to treat. The underlying mechanisms of painful symptoms may be closely associated with hyperglycaemia but a lack of the understanding of its proper aetiology, inadequate relief, development of tolerance and potential toxicity of classical antinociceptives warrant the investigation of the newer agents to relieve this pain. The aim of the present study was to explore the antinociceptive effect of resveratrol on diabetic neuropathic pain and to examine its effect on serum tumour necrosis factor-alpha (TNF-alpha) and whole brain nitric oxide (NO) release. ⋯ Daily treatment with resveratrol (5, 10 and 20 mg/kg body weight; p.o.) for 4 weeks starting from the 4th week of STZ injection significantly attenuated thermal hyperalgesia. Resveratrol also decreased the serum TNF-alpha levels and whole brain NO release in a dose-dependent manner. These results point towards the potential of resveratrol in attenuating diabetic neuropathic pain.