Secondary somatosensory cortex stimulation facilitates the antinociceptive effect of the NO synthase inhibitor through suppression of spinal nociceptive neurons in the rat.
Electrical stimulation of the secondary somatosensory cortex (S-II), which is clinically effective in some chronic pain patients, produces a weak antinociception by itself and also strongly facilitates the antinociceptive effect of the neuronal NO synthase inhibitor 7-nitro-indazole in laboratory animals (rats). The present study thus investigated the mechanisms by which S-II stimulation facilitates the 7-nitro-indazole-induced antinociception. S-II stimulation in combination with 7-nitro-indazole at a subeffective dose, 5 mg/kg, synergistically reduced the number of cells expressing c-Fos in response to intraplantar injection of formalin in the superficial regions (laminae I and II) of the L4 and L5 spinal dorsal horn in conscious rats, although each had no significant effect. A similar synergism produced by S-II stimulation and 7-nitro-indazole was also confirmed in both the first and second phases in the formalin-induced behavioral nociception test. The synergistic antinociception exerted by S-II stimulation in combination with 7-nitro-indazole was resistant to systemic administration of the opioid antagonist naloxone or the alpha-adrenoceptor antagonist phentolamine. In contrast, intrathecally administered methysergide, a serotonin receptor antagonist, at 20 microg/rat, abolished the first-phase, but not the second-phase, antinociception following S-II stimulation in combination with 7-nitro-indazole. These findings suggest that S-II stimulation, in combination with inhibition of neuronal NO synthase, can suppress spinal nociceptive neurons, at least in part through the descending spinal serotonergic pathway, resulting in antinociception.
Kuroda
R
R
Department of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Kinki University, Higashi-Osaka 577-8502, Japan.
Kawao
N
N
Yoshimura
H
H
Umeda
W
W
Takemura
M
M
Shigenaga
Y
Y
Kawabata
A
A
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007278:Injections, Spinal; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000737:chemistry / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D009619:Nociceptors / Q000378:metabolism*; D010146:Pain / Q000378:metabolism; D010147:Pain Measurement; D010646:Phentolamine / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012702:Serotonin Antagonists / Q000494:pharmacology; D013003:Somatosensory Cortex / Q000166:cytology* / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology* / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D004791:Enzyme Inhibitors; D007191:Indazoles; D009292:Narcotic Antagonists; D016760:Proto-Oncogene Proteins c-fos; D012702:Serotonin Antagonists; D009270:Naloxone; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; C080122:7-nitroindazole; D008784:Methysergide; D010646:Phentolamine