Intrathecal oxotremorine affects formalin-induced behavior and spinal nitric oxide synthase immunoreactivity in rats

The present research was undertaken to investigate, by behavioral and immun ohistochemical methods, the effects of intrathecal (ITH) injection of the m uscarinic agonist oxotremorine on the response to the long-lasting nocicept ive stimulus induced by injection of formalin into the rat hind paw. Formal in injection induced a biphasic, pain-induced behavioral response (paw jerk s), as well as an increase in the number of nitric oxide (NO) synthase-labe led neurons in laminae I-III, IV, and X, but not in laminae V-VI. Oxotremor ine (0.1-10 ng, ITH) inhibited paw-jerk frequency in both phases of formali n-induced behavior. The immunohistochemical results showed that ITH-injecte d oxotremorine differently affected the level of NO synthase in lumbar part of the spinal cord: no change or increase after the dose of 1 ng, and a si gnificant reduction of nitric oxide synthase neurons after the higher dose (10 ng). These results evidenced a role of cholinergic system in the modula tion of tonic pain and in nitric oxide synthase expression at the spinal co rd level, which further suggests that these two systems could be involved i n phenomena induced by long-lasting nociceptive stimulation. (C) 1999 Elsev ier Science Inc.