Localization of N-type Ca2+ channels in the rat spinal cord following chronic constrictive nerve injury

Abstract

Previous studies have shown that spinal L-type, N-type, and P-type Ca2+-channel blockers are effective in modulating pain behavior caused nerve injury. In the present work, using the loose ligation of the sciatic nerve model, we characterized the time course of the appearance of tactile and cold allodynia and the corresponding spinal expression of the N-type Ca2+ channel alpha(1B)-subunit after nerve ligation. Within 1 week after ligation, the majority of rats developed a unilateral sensitivity to mechanical stimulation (von Frey filaments), as well as sensitivity to cold, which persisted for 30 days. Immunocytochemical analysis of the spinal cord in sham-operated animals for the alpha(1B)-subunit showed a smooth, moderate staining pattern in the superficial laminae I-II, as well as in ventral alpha-motoneurons. In nerve-ligated animals, an intense, dot-like immunoreactivity in the ipsilateral dorsal horn was observed from 5-20 days after nerve ligation. The most prominent alpha(1B)-subunit upregulation was found in the outer as well as the inner part of lamina II (II(o), II(i)), extending from the medial toward the lateral region of the L4 and L5 spinal segments. The behavioral changes which developed after chronic constriction injury directly correlated with the alpha(1B)-subunit upregulation in the corresponding spinal cord segments. These data suggest that upregulation of the spinal alpha(1B)-subunit may play an important role in the initiation and maintenance of pain state after peripheral nerve injury.