TRPA1 ion channel, expressed in nociceptive primary afferent neurons, modulates excitability of nociceptors, and it may be activated by compounds resulting from oxidative insults. DM (diabetes mellitus) increases 4-HNE production, an endogenous product of oxidative stress, which activates the TRPA1 channel[3]. Chembridge-5861528 is a reversible TRPA1 channel antagonist. Intrathecal (i.t.) administration of Chembridge-5861528 at doses 2.5-5.0 μg/rat markedly attenuated diabetic hypersensitivity, whereas 20 μg of Chembridge-5861528 was needed to produce a weak attenuation of diabetic hypersensitivity with intraplantar (i.pl.) administrations. In controls, i.pl. administration of Chembridge-5861528 (20 μg) produced a weak antihypersensitivity effect at the mustard oil-treated site. I.t. administration of Chembridge-5861528 (10 μg) in controls produced a strong antihypersensitivity effect adjacent to the mustard oil-treated area (site of secondary hyperalgesia)[4].
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