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Our electrophysiological and behavioral evidence demonstrated that PPAR-± activation can acutely inhibit the activity of ASICs in nociceptive DRG neurons. PPAR-± agonist GW7647 decreased the amplitude of proton-activated currents and acidosis-triggered action potentials in rat isolated DRG neurons. Peripheral administration of GW7647 relieved acidosis-evoked nociceptive responses and CFA-induced mechanical hypersensitivity in asics trainers mens rats.
We found that GW7647 exerted a rapid inhibiting effect on peak ASIC currents in rat isolated DRG neurons. The inhibiting effect of GW7647 on ASIC currents was blocked by PPAR-± antagonist, indicating involvement of PPAR-±. It has been shown that DRGs contain both PPAR-± mRNA and PPAR-± immunoreactivity in both small and large neuron [ 2 ]. In twenty neurons that are insensitive to GW7647, PPAR-± may be not expressed in these neurons recorded by ASIC currents. GW7647 has been found to attenuate the depolarization-evoked [Ca 2 ] i in small DRG neurons through PPAR-± [ 36 ].
Pharmacological blockade asics womens running shoes of N-acylethanolamine acid amidase activity and preservation of endogenous PEA suppress visceral pain response elicited by intraperitoneal injections of acetic acid in mice through PPAR-± [ 38 ]. However, this visceral pain response is enhanced in female mice lacking PPAR-± [ 9 ].PPAR-±, belonging to a nuclear receptor super-family, can function directly as a transcription factor that control gene transcription. Genomic effects of PPAR-± have latencies of at least 30 minutes (and up to days) and are associated with changes in protein synthesis [ 12 ]. Moreover, PPAR-± can also act at non-transcriptional targets to produce more rapid effects.