Articles: hyperalgesia.
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Clinical studies of transcutaneous electrical nerve stimulation (TENS) have used a variety of outcome measures to assess its effectiveness, with conflicting results. It is possible that TENS is effective on some measures of pain and not on others. The purpose of this study was to test the hypothesis that TENS reduces primary hyperalgesia of the knee induced by joint inflammation. ⋯ These data suggest that TENS inhibits primary hyperalgesia associated with inflammation in a time-dependent manner after inflammation has already developed during both acute and chronic stages.
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Using a new animal model of postoperative pain we recently developed, we investigated whether the selective cyclooxygenase-2 (COX-2) inhibitor parecoxib sodium, and the analgesic tramadol hydrochloride, attenuated mechanical primary hyperalgesia induced by minor surgery on the rat tail. ⋯ We have shown that the hyperalgesia in our model of postoperative pain is responsive to treatment with the analgesic tramadol, but it is not responsive to the selective COX-2 inhibitor parecoxib at the doses we used.
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Neuroimmunomodulation · Jan 2007
Role of histamine H3 and H4 receptors in mechanical hyperalgesia following peripheral nerve injury.
Histamine is a chemical mediator that acts at four known types of histamine receptors and has been widely implicated in the development of nociception and neuropathic pain. Blocking histamine H(1) and H(2) receptors has been shown to reduce hyperalgesia following nerve injury, but the role of histamine H(3) and H(4) receptors in neuropathic pain has not been studied. Here, we used blockers of histamine H(3) and H(4) receptors to assess their effects on neuropathic pain behavior and mast cell numbers following peripheral nerve injury. In addition, we assessed the effect of activating H(4) receptors on neuropathic pain behavior. ⋯ We propose that the increase in mechanical hyperalgesia produced by thioperamide and JNJ 7777120 and the decrease in mechanical hyperalgesia produced by VUF 8430 may represent a direct effect of these agents on mechanospecific primary afferents, or an indirect effect of these agents via injury-induced inflammation.
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Metamizol (dipyrone) and other nonsteroidal anti-inflammatory drugs (NSAIDs) induce antinociception by acting upon peripheral tissues and upon central nervous system structures, notably the periaqueductal grey matter (PAG) and the spinal cord. Inflammation-induced hyperalgesia is prevented by spinal application of NSAIDs before the inflammation, but once central sensitization is established the spinal effect of NSAIDs is uncertain. The present study examines whether the action upon the PAG contributes to the attenuation of inflammation-induced spinal hyperalgesia by NSAIDs. ⋯ More interestingly, microinjection of metamizol into PAG when hyperexcitability was fully developed depressed neuronal responses down to baseline for approximately 1 h. The effect of PAG metamizol was reversed by microinjection of a GABA(A) agonist into the rostral ventromedial medulla (RVM), which indicates that RVM relays the metamizol effect from PAG onto the spinal cord. These results suggest that, upon clinical administration of NSAIDs, a joint action upon PAG and spinal cord contributes to preventing the development of hyperalgesia but it is mainly the action upon PAG which contributes to reducing fully established hyperalgesia.
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Comparative Study
The voltage-gated sodium channel Na(v)1.9 is an effector of peripheral inflammatory pain hypersensitivity.
We used a mouse with deletion of exons 4, 5, and 6 of the SCN11A (sodium channel, voltage-gated, type XI, alpha) gene that encodes the voltage-gated sodium channel Na(v)1.9 to assess its contribution to pain. Na(v)1.9 is present in nociceptor sensory neurons that express TRPV1, bradykinin B2, and purinergic P2X3 receptors. In Na(v)1.9-/- mice, the non-inactivating persistent tetrodotoxin-resistant sodium TTXr-Per current is absent, whereas TTXr-Slow is unchanged. ⋯ Pain hypersensitivity elicited by intraplantar administration of prostaglandin E2, bradykinin, interleukin-1beta, capsaicin, and P2X3 and P2Y receptor agonists, but not NGF, is either reduced or absent in Na(v)1.9-/- mice, whereas basal thermal and mechanical pain sensitivity is unchanged. Thermal, but not mechanical, hypersensitivity produced by peripheral inflammation (intraplanatar complete Freund's adjuvant) is substantially diminished in the null allele mutant mice, whereas hypersensitivity in two neuropathic pain models is unchanged in the Na(v)1.9-/- mice. Na(v)1.9 is, we conclude, an effector of the hypersensitivity produced by multiple inflammatory mediators on nociceptor peripheral terminals and therefore plays a key role in mediating peripheral sensitization.