Articles: hyperalgesia.
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Anesthesia and analgesia · Oct 2009
The peripheral antinociceptive effects of endomorphin-1 and kynurenic acid in the rat inflamed joint model.
Several data suggest that both opioid and N-methyl-d-aspartate (NMDA) receptors are localized at the peripheral level, and drugs acting on these receptors may produce antinociception after topical administration; however, the antinociceptive effect of endogenous ligands at these receptors is poorly clarified. Our goal in this study was to determine the antinociceptive potency of the endogenous opioid peptide, endomorphin-1 (EM1), and the endogenous NMDA receptor antagonist, kynurenic acid (KYNA), and their interaction at the peripheral level in the rat inflamed joint model. ⋯ Peripherally administered endogenous opioid agonist and NMDA receptor antagonist ligands might be beneficial in inflammatory pain. Because both drugs barely cross the blood-brain barrier, their local administration causes no central side effects.
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Nitric oxide, which has been implicated in the development of hyperalgesia in the spinal system, has not been systematically studied in the trigeminal system, especially in the context of inflammatory muscle pain condition. In this study, we investigated the functional role of centrally released nitric oxide in the pathogenesis of orofacial muscle pain. Specifically, we examined the contribution of neuronal, inducible and endothelial nitric oxide synthases, nNOS, iNOS and eNOS, respectively, in mediating masseter hypersensitivity under acute inflammatory condition. ⋯ The expression of all three nitric oxide synthases was significantly up-regulated 30-60 min following capsaicin stimulation, which paralleled the time course of the development of capsaicin-induced masseter hypersensitivity. Pretreatment with each NOS inhibitor significantly attenuated the masseter hypersensitivity. These data showed that all three NOS in the Vc are functionally important for the development of craniofacial muscle hyperalgesia and suggest that the three NOS are closely orchestrated to regulate the level of nitric oxide under normal and pathologic conditions.
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J. Pharmacol. Exp. Ther. · Oct 2009
Comparative StudyThermal hyperalgesia via supraspinal mechanisms in mice lacking glutamate decarboxylase 65.
Gamma-aminobutyric acid, which is synthesized by two isoforms of glutamate decarboxylase (GAD), inhibits the transfer of nociceptive signals from primary afferent fibers to the central nervous system. However, the roles of a 65-kDa isoform of GAD (GAD65)-mediated GABA in nociceptive processing are less clear. This study tested whether partial reductions in GABAergic inhibitory tone by GAD65 gene knockout [GAD65(-/-)] would contribute to the regulation of pain threshold in mice. ⋯ There was no genotype difference in responses to chemical inflammatory nociception (formalin test and carrageenan test). Although properties of the phasic component of inhibitory postsynaptic currents were similar in both genotypes, tonic inhibition was significantly reduced in GAD65(-/-) mice. These results support the hypothesis that GAD65-mediated GABA synthesis plays relatively small but significant roles in nociceptive processing via supraspinal mechanisms.
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Behavioural pharmacology · Oct 2009
The selective metabotropic glutamate receptor 7 allosteric agonist AMN082 inhibits inflammatory pain-induced and incision-induced hypersensitivity in rat.
This study characterized the contribution of metabotropic glutamate receptor 7 (mGlu7 receptor) activation to the development of inflammatory hyperalgesia and allodynia, using a novel, systemically active mGlu7 receptor allosteric agonist, N, N'-dibenzhydrylethane-1,2-diamine dihydrochloride (AMN082). The effects of AMN082 (0.1, 1 or 5 mg/kg, intraperitoneally; 5 or 50 nmol, intrathecally) or diclofenac (5 mg/kg, intraperitoneally) administered 30 min preprocedure or 3 h postprocedure on hindpaw withdrawal latency (in seconds) to thermal stimulation, and response threshold (in grams) to mechanical stimulation, were measured in adult rats (n = 6-8 per group) before and up to 24 h after intradermal injection of carrageenan into the hindpaw or hindpaw incision. ⋯ Intrathecal injection of AMN082 postcarrageenan and postsurgery also significantly attenuated thermal hyperalgesia. Enhancing endogenous mGlu7 receptor activity inhibits postinjury stimulus-evoked hypersensitivity and may be of therapeutic benefit for the treatment of inflammatory and incision-induced pain.
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Sigma-1 receptor (sigma(1)R) is expressed in key CNS areas involved in nociceptive processing but only limited information is available about its functional role. In the present study we investigated the relevance of sigma(1)R in modulating nerve injury-evoked pain. For this purpose, wild-type mice and mice lacking the sigma(1)R gene were exposed to partial sciatic nerve ligation and neuropathic pain-related behaviors were investigated. ⋯ In addition, in contrast to wild-type mice, sigma(1)R knockout mice did not show increased phosphorylation of ERK in the spinal cord after sciatic nerve injury. Both wind-up and ERK activation have been related to mechanisms of spinal cord sensitization. Our findings identify sigma(1)R as a constituent of the mechanisms modulating activity-induced sensitization in pain pathways and point to sigma(1)R as a new potential target for drugs designed to alleviate neuropathic pain.