PRIMARY SENSORY NEURONS EXHIBIT ALTERED GENE-EXPRESSION IN A RAT MODEL OF NEUROPATHIC PAIN

Using a number of complementary anatomical and molecular techniques, we studied the effects of chronic constriction injury (CCI), a model of partial nerve injury that elicits behavioral hyperalgesia, on primary sensory neurons in the rat. Dorsal root ganglia taken from animals with 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 7-14 day time frame, both CGRP and SP mRNAs fell to half their normally abundant constitutive levels of expression. The most dramatic change in expression occurred for GAL, NPY and VIP mRNAs which all rose rapidly (day 3) from non-detectable levels. Similar alterations in gene expression have been described after complete sciatic nerve transection or crush.