Effect of administration of high dose intrathecal clonidine or morphine prior to sciatic nerve section on c-Fos expression in rat lumbar spinal cord

• Published in: Neuroscience Vol. 68; no. 4; pp. 1219 - 1227
• Main Authors: Luo, L., Ji, R.-R., Zhang, Q., Iadarola, M.J., Hökfelt, T., Wiesenfeld-Hallin, Z.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.10.1995; Elsevier
• Subjects: Adrenergic alpha-Agonists - administration & dosage; Adrenergic alpha-Agonists - pharmacology; Animals; Biological and medical sciences; Clonidine - administration & dosage; Clonidine - pharmacology; Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction; Immunohistochemistry; Injections, Spinal; Male; Medical sciences; Medicin och hälsovetenskap; Morphine - administration & dosage; Morphine - pharmacology; Narcotics - administration & dosage; Narcotics - pharmacology; Nervous system (semeiology, syndromes); Neurology; Proto-Oncogene Proteins c-fos - biosynthesis; Rats; Rats, Sprague-Dawley; Sciatic Nerve - physiology; Spinal Cord - drug effects; Spinal Cord - metabolism; LI-like immunoreactivity; α2-Adrenergic receptor; Nervous system diseases; Agonist; Spinal cord; Rat; Rodentia; Central nervous system; Morphine; Gene expression; Peripheral neuropathy; Prevention; Vertebrata; Experimental disease; Mammalia; Animal; Sciatic nerve; Protooncogene; Immediate early gene
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/0306-4522(95)00197-Q

The effect of moderate and high intrathecal doses of clonidine, an α 2 adrenoceptor agonist, or a high dose of morphine on sciatic nerve section-induced expression of c-Fos-like immunoreactivity was studied in laminae I and II of the dorsal horn and laminae VII and IX of the ventral horn of rat lumbar spinal cord. c-Fos-like immunoreactivity was examined by immunohistochemistry in normal rats (group 1), rats implanted with an intrathecal catheter with its tip on the lumbar spinal cord (group 2), injected with 10 μg (group 3) or 50 μg (group 4) clonidine intrathecally 3 h before being killed. In other groups, saline, 10 or 50 μg clonidine or 30 μg morphine was injected 1 h before unilateral nerve section, and the expression of c-Fos-like immunoreactivity was examined 2 h after axotomy. Few labeled neurons were found in normal controls. The intrathecal catheter itself caused a significant increase in bilateral c-Fos-like immunoreactivity in spinal dorsal and ventral horn compared to normals. The level of c-Fos-like immunoreactivity after 10 or 50 μg intrathecal clonidine was similar as in the intrathecal catheter group. Sciatic nerve section caused a significant ipsilateral increase in c-Fos-like immunoreactivity in the dorsal horn compared to the intact side in rats injected with saline. Pretreatment with 10 or 50 μg clonidine did not reduce sciatic nerve section-induced expression of c-Fos-like immunoreactivity, but instead caused a significant bilateral increase in c-Fos-like immunoreactivity. The lower dose of clonidine increased c-Fos-like immunoreactivity bilaterally 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 with 30 μg intrathecal morphine prevented the expression of c-Fos-like immunoreactivity following axotomy in dorsal and ventral horn bilaterally, resulting in a similar level of labeling as in normal controls. Thus, the present results indicate that nerve injury induced the expression of c-Fos-like immunoreactivity in spinal cord, and that this can be prevented by a high intrathecal dose of morphine. In contrast, intrathecal clonidine potentiated nerve section-induced c-Fos-like immunoreactivity expression bilaterally, which might be due to a synergistic effect between clonidine and nerve section. The possible role of the expression of c-Fos-like immunoreactivity in experimental neuropathic pain is discussed.