Involvement of the nitric oxide/(C)GMP/K(ATP) pathway in antinociception induced by exercise in rats

Physical exercise is responsible for increasing the nociceptive threshold. The present study aimed to investigate the involvement of the nitric oxide/(C)GMP/K(ATP) pathway in antinociception induced by acute aerobic exercise (AAc) in rats.

Wistar rats performed exercise in a rodent treadmill, according to an AAc protocol. The nociceptive threshold was measured by mechanical and thermal nociceptive tests (paw-withdrawal, tail-flick and face-flick). To investigate the involvement of the NO/(C)GMP/K(ATP) pathway the following nitric oxide synthase (NOS) unspecific and specific inhibitors were used: N-nitro-l-arginine (NOArg), Aminoguanidine, N(5)-(1-Iminoethyl)-l-ornithine dihydrocloride (L-NIO), N(omega)-Propyl-l-arginine (L-NPA); guanylyl cyclase inhibitor, 1H-[1,2,4]oxidiazolo[4,3-a]quinoxalin-1-one (ODQ); and K(ATP) channel blocker, Glybenclamide; all administered subcutaneously at a dose of 2mg/kg 10min before exercise started. Plasma and cerebrospinal fluid (CSF) nitrite levels were determined by spectrophotometry.

In the paw-withdrawal, tail-flick and face-flick tests, the AAc protocol produced antinociception, which lasted for more than 15min. This effect was significantly reversed (P<0.05) by NOS specific and unspecific inhibitors, guanylyl cyclase inhibitor (ODQ) and K(ATP) channel blocker (Glybenclamide). Acute exercise was also responsible for increasing nitrite levels in both plasma and cerebrospinal fluid.

Taken together, these results suggest that the NO/(C)GMP/K(ATP) pathway participates in antinociception induced by exercise.