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

Life Sci. 2010 Mar 27;86(13-14):505-9. doi: 10.1016/j.lfs.2010.02.004. Epub 2010 Feb 11.

Abstract

Aims: 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.

Main methods: 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.

Key findings: 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.

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

MeSH terms

  • Animals
  • Cyclic GMP / metabolism*
  • Glutamic Acid / metabolism
  • Male
  • Nitric Oxide / metabolism*
  • Nitrites / blood
  • Nitrites / cerebrospinal fluid
  • Pain Measurement
  • Physical Conditioning, Animal / physiology*
  • Potassium Channels / metabolism*
  • Rats
  • Rats, Wistar
  • Signal Transduction*

Substances

  • Nitrites
  • Potassium Channels
  • mitochondrial K(ATP) channel
  • Nitric Oxide
  • Glutamic Acid
  • Cyclic GMP