The role of TRPA1 in muscle pain and mechanical hypersensitivity under inflammatory conditions in rats.

Transient receptor potential cation channel, subfamily A, member 1 (TRPA1) is expressed in muscle afferents and direct activation of these receptors induces acute mechanical hypersensitivity. However, the functional role of TRPA1 under pathological muscle pain conditions and mechanisms by which TRPA1 mediate muscle pain and hyperalgesia are not clearly understood. Two rodent behavioral models validated to assess craniofacial muscle pain conditions were used to study ATP- and N-Methyl-D-aspartate (NMDA)-induced acute mechanical hypersensitivity and complete Freund's adjuvant (CFA)-induced persistent mechanical hypersensitivity. The rat grimace scale (RGS) was utilized to assess inflammation-induced spontaneous muscle pain. Behavioral pharmacology experiments were performed to assess the effects of AP18, a selective TRPA1 antagonist under these conditions. TRPA1 expression levels in trigeminal ganglia (TG) were examined before and after CFA treatment in the rat masseter muscle. Pre-treatment of the muscle with AP18 dose-dependently blocked the development of acute mechanical hypersensitivity induced by NMDA and α,ß-methylene adenosine triphosphate (αßmeATP), a specific agonist for NMDA and P2X3 receptor, respectively. CFA-induced mechanical hypersensitivity and spontaneous muscle pain responses were significantly reversed by post-treatment of the muscle with AP18 when CFA effects were most prominent. CFA-induced myositis was accompanied by significant up-regulation of TRPA1 expression in TG. Our findings showed that TRPA1 in muscle afferents plays an important role in the development of acute mechanical hypersensitivity and in the maintenance of persistent muscle pain and hypersensitivity. Our data suggested that TRPA1 may serve as a downstream target of pro-nociceptive ion channels, such as P2X3 and NMDA receptors in masseter afferents, and that increased TRPA1 expression under inflammatory conditions may contribute to the maintenance of persistent muscle pain and mechanical hyperalgesia. Mechanistic studies elucidating transcriptional or post-translational regulation of TRPA1 expression under pathological pain conditions should provide important basic information to further advance the treatment of craniofacial muscle pain conditions.

STZ treatment induced apoptosis of retinal cells and effect of up-regulation of calcitonin gene related peptide in rats.

BACKGROUND: Evidence indicates an early neural injury of the retinal cells in diabetes. The aim of the current study was to investigate the apoptosis of the retinal cells and the relationship with CGRP. MATERIALS AND METHODS: The diabetes was induced by treatment of STZ, using which the apoptosis of retinal cells, the caspase-3 activity and the expression of CGRP in the retina and the serum were examined. Capsaicin (20mg/kg) was given to the animals to induce up-regulation of the CGRP. Apoptosis and CGRP in the retina were also examined in an in vitro study. RESULTS AND CONCLUSION: The apoptosis of the retinal cells was confined to the GCL, in which CGRP was normally located. A significant increase in the apoptosis ratio (P<0.05) was observed in the STZ treated animals and high glucose incubated retina, with reductions of CGRP. The pre-treatment with capsaicin effectively up-regulated CGRP and its encoding mRNA and attenuated the cell apoptosis and caspase-3 activity in the retina. The increases of the cell apoptosis in the retina may be related to the down-regulation of endogenous CGRP in diabetes. Capsaicin may attenuate the apoptosis of the retina cells at early times of diabetes, via up-regulation of CGRP.