CHANGES IN NEURONAL MARKERS IN A MONONEUROPATHIC RAT MODEL - RELATIONSHIP BETWEEN NEUROPEPTIDE-Y, PREEMPTIVE DRUG-TREATMENT AND LONG-TERM MECHANICAL HYPERALGESIA

Using the chronic constriction model (CCI) of Bennett and Xie (1988), changes in the lumbar spinal cord in neuropeptides and lectin IB4 were examined at 28 days post-nerve constriction and were compared with th e degree of mechanical hyperalgesia. Animals following nerve ligation were significantly more hyperalgesic than sham-operated animals (P < 0 .0001). Lectin IB4, a marker of primary afferent C fibres, showed a qu alitative decrease in staining intensity in laminae 1-2 with ligation compared with both the unoperated contralateral side and with sham ani mals. Using fluorescent immunohistochemistry to quantify changes in ne uropeptides in the dorsal horn we found that substance P showed signif icant decreases with ligation compared to sham operation (P < 0.002). CGRP and galanin showed no significant changes in laminae 1-2 compared to sham-operated animals. Neuropeptide Y (NPY) showed no significant changes in intensity in laminae 1-2; however, in laminae 3-4 there was a significant increase with nerve ligation compared to sham (P < 0.00 5). We examined how pre-emptive drug treatment affected these neuronal markers at 28 days. We used (1) clonidine, an alpha(2)-adrenoreceptor agonist (1 mg/kg, i.p.), (2) morphine, a mu-opioid agonist (5 mg/kg, i.p.) or (3) MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonis t (0.3 mg/kg, s.c.) administered 30 min prior and 6 h following nerve ligation or sham-operation. Hyperalgesia in the ligated group at 28 da ys was suppressed by treatment with pre-emptive clonidine (P = 0.003) or MK-801 (P = 0.003) but not morphine. With the exception of NPY ther e was no effect of pre-emptive drug treatment on any neuronal marker e xamined. Pre-emptive MK-801 reduced the magnitude of the increase in N PY in laminae 3-4 in the ligated group (P < 0.005) and clonidine showe d a similar trend but this did not reach significance. Morphine had no effect on NPY staining. There was a significant correlation between t he increase in NPY staining in laminae 3-4 and the degree of hyperalge sia (r = 0.6, P < 0.001). These results suggest that the increased NPY expression in laminae 3-4 of the spinal cord (the territory of the my elinated sensory input) may be crucial to the development of hyperalge sia in this model.