The Chronic Constriction Injury (CCI), a model of nerve injury in the rat, is produced by tying loose ligatures of 4-0 chromic gut suture around the sciatic nerve. The CCI elicits behavioral hyperalgesia and allodynia. As such, the CCI resembles human neuropathies associated with several clinical syndromes including, causalgia and reflex sympathetic dystrophy. Using a number of complementary anatomical and molecular techniques, we studied the effects of the CCI on the peripheral nervous system of the rat. Dorsal root ganglia taken from animals with the CCI were analyzed for alterations in mRNA levels encoding growth associated protein-43 (GAP-43), calcitonin gene related peptide (CGRP), galanin (GAL), neuropeptide Y (NPY), substance P (SP), and vasoactive intestinal polypeptide (VIP). We found that GAP-43 expression increased 3-fold, peaking between 7 and 14 days after development of the CCI. However, within this same 7 to 14 day time frame, both CGRP and SP mRNAs fell to half their normally abundant basal levels. The most dramatic change in expression occurred for GAL, NPY and VIP mRNAs, which all rose rapidly (1 day) from nearly non-expressed states. These data suggest that gene expression is modified to increase production of molecules responding to nerve injury and necessary for regrowth, and to decrease production of molecules involved in normal neurotransmission.
