SPINAL-CORD INJURY AND ANTI-NGF TREATMENT RESULTS IN CHANGES IN CGRP DENSITY AND DISTRIBUTION IN THE DORSAL HORN IN THE RAT

Spinal cord injury (SCI) results in chronic pain states in which the u nderlying mechanism is poorly understood. To begin to explore possible mechanisms, calcitonin gene-related peptide (CGRP), a neuropeptide co nfined to fine primary afferent terminals in laminae I and II in the d orsal horn of the spinal cord and implicated in pain transmission, was selected. Immunocytochemical techniques were used to examine the temp oral and spatial distribution of CGRP in the spinal cord following T-1 3 spinal cord hemisection in adult male Sprague-Dawley rats compared t o that seen in sham controls. Spinal cords from both hemisected and sh am control groups (N = 5, per time point) were examined on postoperati ve day (POD) 3, 5, 7, 14, and 108 following surgery. Sham operated rat s displayed CGRP immunoreaction product in laminae I and II outer, Lis sauer's tract, dorsal roots, and motor neurons of the ventral horn. In the hemisected group, densiometric data demonstrated an increased dep osition of reaction product that was statistically significant, in lam inae III and TV, both ipsilateral and contralateral to the lesion that extended at least two segments rostral and caudal to the hemisection site by POD 14, and remained significantly elevated as long as POD 108 . Since upregulation alone of CGRP would occur in an acute temporal wi ndow (by 2 to 3 days following spinal injury), these results are inter preted to be invasion of laminae III and IV by sprouting of CGRP conta ining fine primary afferents. Intrathecal delivery of antibodies again st purified 2.5S nerve growth factor for 14 days to the hemisected gro up resulted in CGRP density in laminae I through IV that was significa ntly less than that seen in untreated or vehicle treated hemisected gr oups and to sham controls. These data indicate changes in density and distribution of CGRP following spinal hemisection that can be manipula ted by changes in endogenous levels of NGF. These observations suggest possible strategies for intervention in the development of various pa in states in human SCI. (C) 1997 Academic Press.