EFFECT OF ADMINISTRATION OF HIGH-DOSE INTRATHECAL CLONIDINE OR MORPHINE PRIOR TO SCIATIC-NERVE SECTION ON C-FOS EXPRESSION IN RAT LUMBAR SPINAL-CORD

The effect of moderate and high intrathecal doses of clonidine, an alp ha(2) adrenoceptor agonist, or a high dose of morphine on sciatic nerv e section-induced expression of c-Fos-like immunoreactivity was studie d in laminae I and II of the dorsal horn and laminae VIII and IX of th e ventral horn of rat lumbar spinal cord. c-Fos-like immunoreactivity was examined by immunohistochemistry in normal rats (group 1), rats im planted with an intrathecal catheter with its tip on the lumbar spinal cord (group 2), injected with 10 mu g (group 3) or 50 mu g (group 4) clonidine intrathecally 3 h before being killed. In other groups, sali ne, 10 or 50 mu g clonidine or 30 mu g morphine was injected 1 h befor e unilateral nerve section, and the expression of c-Fos-like immunorea ctivity was examined 2 h after axotomy. Few labeled neurons were found in normal controls. The intrathecal catheter itself caused a signific ant increase in bilateral c-Fos-like immunoreactivity in spinal dorsal and ventral horn compared to normals. The level of c-Fos-like immunor eactivity after 10 or 50 mu g intrathecal clonidine was similar as in the intrathecal catheter group. Sciatic nerve section caused a signifi cant ipsilateral increase in c-Fos-like immunoreactivity in the dorsal horn compared to the intact side in rats injected with saline. Pretre atment with 10 or 50 mu g clonidine did not reduce sciatic nerve secti on-induced expression of c-Fos-like immunoreactivity, but instead caus ed a significant bilateral increase in c-Fos-like immunoreactivity. Th e lower dose of clonidine increased c-Fos-like immunoreactivity bilate rally in laminae I and II, the higher dose in both dorsal and ventral horn, compared to animals injected with saline prior to nerve section or rats with intact nerves injected with clonidine. However, the level of c-Fos-like immunoreactivity after clonidine was in general higher on the axotomized than on the intact side. In contrast, pretreatment w ith 30 mu g intrathecal morphine prevented the expression of c-Fos-lik e immunoreactivity following axotomy in dorsal and ventral horn bilate rally, resulting in a similar level of labeling as in normal controls. Thus, the present results indicate that nerve injury induced the expr ession of c-Fos-like immunoreactivity in spinal cord, and that this ca n be prevented by a high intrathecal dose of morphine. In contrast, in trathecal clonidine potentiated nerve section-induced c-Fos-like immun oreactivity expression bilaterally, which might be due to a synergisti c effect between clonidine and nerve section. The possible role of the expression of c-Fos-like immunoreactivity in experimental neuropathic pain is discussed.