Articles: hyperalgesia.
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The CCR2/CCL2 system has been identified as a regulator in the pathogenesis of neuropathy-induced pain. However, CCR2 target validation in analgesia and the mechanism underlying antinociception produced by CCR2 antagonists remains poorly understood. In this study, in vitro and in vivo pharmacological approaches using a novel CCR2 antagonist, AZ889, strengthened the hypothesis of a CCR2 contribution to neuropathic pain and provided confidence over the possibilities to treat neuropathic pain with CCR2 antagonists. ⋯ Overall, this study strengthens the important role of CCR2 in neuropathic pain and highlights feasibility that interfering on this mechanism at the spinal level with a selective antagonist can provide new analgesia opportunities.
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Previous studies have shown that the TRPV1 ion channel plays a critical role in the development of heat hyperalgesia after inflammation, as inflamed TRPV1-/- mice develop mechanical allodynia but fail to develop thermal hyperalgesia. In order to further investigate the role of TRPV1, we have used an ex vivo skin/nerve/DRG preparation to examine the effects of CFA-induced-inflammation on the response properties of TRPV1-positive and TRPV1-negative cutaneous nociceptors. ⋯ Results obtained here suggest that increased heat sensitivity in TRPV1-negative CPM fibers alone following inflammation is insufficient for the induction of heat hyperalgesia. On the other hand, TRPV1-positive CH fibers appear to play an essential role in this process that may include both afferent and efferent functions.
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The UV-B pain model utilizes ultraviolet light to induce a small area of inflammation allowing assessment of mechanical and thermal thresholds. Pharmacologic testing has mainly focused on reduction of primary hyperalgesia, although the effect of analgesics on secondary hyperalgesia has also been investigated. The model requires an instrument to precisely generate controlled UV-B tissue hyperalgesia. ⋯ Tissue is then assessed for inflammation using color Doppler imaging or flare measurements. Heat pain thresholds and pain tolerance are often evaluated using a commercially available thermal sensory testing device. Analgesics can be administered to determine the influence on these clinical endpoints.
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Am. J. Physiol. Gastrointest. Liver Physiol. · Jan 2010
Transient receptor potential ankyrin-1 has a major role in mediating visceral pain in mice.
The excitatory ion channel transient receptor potential ankyrin-1 (TRPA1) is prominently expressed by primary afferent neurons and is a mediator of inflammatory pain. Inflammatory agents can directly activate [e.g., hydroxynonenal (HNE), prostaglandin metabolites] or indirectly sensitize [e.g., agonists of protease-activated receptor (PAR(2))] TRPA1 to induce somatic pain and hyperalgesia. However, the contribution of TRPA1 to visceral pain is unknown. ⋯ Direct activation of TRPA1 causes visceral hyperalgesia, and TRPA1 mediates PAR(2)-induced hyperalgesia. TRPA1 deletion markedly reduces colitis-induced mechanical hyperalgesia in the colon. Our results suggest that TRPA1 has a major role in visceral nociception and may be a therapeutic target for colonic inflammatory pain.
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Although cold hypersensitivity is a well-documented phenomenon in animals and humans with inflammatory and neuropathic pain, little is known about the presence of cold hyperalgesia after surgery. Therefore, we studied primary cold hyperalgesia after a surgical incision in mice. ⋯ The present data give strong evidence that a surgical incision does not cause cold hyperalgesia. Furthermore, a lack of cold hyperalgesia in unrestrained male and female mice after incision was not due to increased skin temperature after incision. Finally, we demonstrated that in contrast to a surgical incision, inflammation and nerve injury generate intense cold hyperalgesia and an increase in skin temperature, suggesting that different mechanisms are involved in surgical and inflammatory or neuropathic pain.