MODULATION OF NEUROTRANSMITTER RECEPTORS FOLLOWING UNILATERAL L1-S2 DEAFFERENTATION - NK1, NK3, NMDA, AND 5HT1A RECEPTOR-BINDING AUTORADIOGRAPHY

Following surgical deafferentation of the spinal cord, cut dorsal roots degenerate, and spared projections compensate for this loss by collateral sprouting (reactive reinnervation). Light microscopic immunocytochemistry has shown sprouting by selected undamaged intraspinal projections, including those that express the transmitters substance P and serotonin. Quantitative immunoelectron microscopy supports these results by demonstrating loss and subsequent recovery of substance P-containing terminals and an increase in serotonin-containing terminals. To test the hypothesis that changes in afferent innervation modulate neurotransmitter receptors on second-order neurons, we used receptor binding autoradiography in this model. Adult rats were subjected to L1-S2 unilateral dorsal rhizotomy and killed at 1, 2, 6, or > 20 weeks after surgery. Receptor binding densities of tachykinin (neurokinins-l and -3), glutamate (N-methyl-D-aspartate), and serotonin (serotonin-la) receptors were assayed in the lumbar dorsal horn. Neurokinin-l binding density was increased in lamina II of the deafferented side by 1 week after surgery, remained elevated at 2 weeks, and returned to control values by 6 weeks. Neurokinin 3 binding density was elevated at 2 weeks and then returned to control levels. N-methyl-D-aspartate receptor binding showed slight but not statistically significant increased binding density at 6 and at > 20 weeks. No significant changes were found in serotonin-la receptor binding density. The elevations in tachykinin receptor binding density occur when afferents in the dorsal horn are degenerating and suggest reactive up-regulation of the receptor. The return to normal levels coincides with reactive reinnervation in the spinal cord, which restores synaptic numbers. Changes in N-methyl-D-aspartate binding occur much later than the restitution of synaptic numbers but may indicate a role for this receptor in synaptic stabilization following reactive reinnervation. (C) 1995 Wiley-Liss, Inc.