The effects of intraspinal L-NOARG or SIN-1 on the control by descending pathways of incisional pain in rats

Life Sci. 2005 Mar 11;76(17):1939-51. doi: 10.1016/j.lfs.2004.08.038. Epub 2005 Jan 27.

Abstract

The modulation by spinal nitric oxide (NO) of descending pathways travelling through the dorsal lateral funiculus (DLF) is a mechanism proposed for the antinociceptive effects of drugs that changes the NO metabolism. In this study we confirm that a surgical incision in the mid-plantar hind paw of rats reduces the threshold to mechanical stimulation with von Frey filaments. The incisional pain was further increased in rats with ipsilateral DLF lesion. Intrathecal L-NOARG (50-300 microg), or SIN-1 (0.1-5.0 microg) reduced, while SIN-1 (10 and 20 microg) intensified the incisional pain in rats with sham or effective lesion of the DLF. Stimulation of the dorsal raphe (DRN) or anterior pretectal (APtN) nuclei with stepwise increased electrical currents (7, 14, 21, 28 and 35 microA r.m.s.) produced a current-related reduction of the incisional pain. These nuclei activate pain inhibitory pathways that descend to the spinal cord mainly through the DLF. Intrathecal SIN-1 (5 microg) reduced, SIN-1 (20 microg) decreased and L-NOARG (150 microg) did not change the EC50 for the DRN or APtN stimulation-induced reduction of incisional pain. We conclude that the antinociceptive effects of L-NOARG or low doses of SIN-1 are independent on the activity of descending pain control pathways travelling via the DLF, but the antinociceptive effect of stimulating electrically the DRN or APtN can be summated to the effect of low dose of SIN-1 or overcome by the high dose of SIN-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesia*
  • Animals
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Efferent Pathways / drug effects*
  • Efferent Pathways / physiopathology
  • Electric Stimulation
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / pharmacology*
  • Hindlimb
  • Injections, Spinal
  • Male
  • Mesencephalon / drug effects
  • Mesencephalon / physiopathology
  • Molsidomine / administration & dosage
  • Molsidomine / analogs & derivatives*
  • Molsidomine / pharmacology*
  • Nitric Oxide Donors / administration & dosage
  • Nitric Oxide Donors / pharmacology*
  • Nitroarginine / administration & dosage
  • Nitroarginine / pharmacology*
  • Pain / drug therapy
  • Pain / prevention & control
  • Pain Threshold / drug effects
  • Raphe Nuclei / drug effects
  • Raphe Nuclei / physiopathology
  • Rats
  • Rats, Wistar
  • Spinal Cord / drug effects
  • Spinal Cord / physiopathology
  • Spinal Cord / surgery

Substances

  • Enzyme Inhibitors
  • Nitric Oxide Donors
  • Nitroarginine
  • linsidomine
  • Molsidomine