Pain
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CGRP(8-37) is a truncated version of calcitonin gene-related peptide (CGRP) that binds to the CGRP receptor with similar affinity but does not activate the receptor and is a highly selective CGRP receptor antagonist. CGRP and activation of its receptor appear to play a role in peripheral inflammatory and neuropathic models of pain although there is considerable controversy. The aim of this study was to examine possible anti-nociceptive effects of CGRP(8-37) on a model of chronic central neuropathic pain known to develop weeks after spinal hemisection. ⋯ The sham control groups demonstrated no statistically significant difference at any dose of CGRP(8-37) when compared to pre-surgical baseline values. In conclusion, CGRP(8-37) is effective in abolishing mechanical and thermal allodynia produced by spinal hemisection. Consequently, the CGRP receptor may play a role in chronic central neuropathic pain and offers a novel therapeutic approach to managing chronic central pain.
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Although much attention has been focused in recent years on nitric oxide synthase (NOS) as an enzyme intimately involved in many types of nociceptive signaling, the enzyme heme oxygenase (HO) has received little attention. Yet, HO produces gaseous second messenger molecule CO which, like NO, has proven to be an important neurotransmitter in the CNS. In these studies we provide detailed evidence that HO activity is critical to formalin-induced licking behavior in mice. ⋯ Mice with a targeted disruption of the HO-2 gene were found to have greatly reduced licking times. Furthermore, Sn-P did not further reduce licking times when administered to HO-2 knockout animals. Taken together our evidence indicates that HO plays an important role in nociceptive signaling related to inflammatory-type pain, and that HO-2 is the isozyme mediating this nociception.
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This study examined the release of several amino acids after induction of knee joint inflammation in rats using kaolin and carrageenan. During the initial 10-min collection after knee joint injection with the irritants, the concentration of glutamate and the nitric oxide metabolites, arginine and citrulline, doubled. ⋯ Direct knee joint administration of lidocaine prevented the increases in amino acid concentration measurable by microdialysis probe inserted into the joint. These data suggest the possibility that glutamate may be released by neuronal endings in the joint.