Glutamate immunocytochemistry in the dorsal horn after injury or stimulation of the sciatic nerve of rats.

Glutamate is a major neurotransmitter of fine afferent fibers to the spinal cord. Neuropeptides are also released by the same fibers. We explored, by quantitative immunocytochemistry, the effects of two experimental manipulations of peripheral nerves on the levels of these two classes of mediators. Glutamate levels in the superficial dorsal horn of rats increased after chronic loose ligature of the sciatic nerve, a model for hyperpathic peripheral neuropathy. A similar increase was observed acutely, after stimulation of C fibers, but not A fibers, in the sciatic nerve. In contrast, immunostaining for substance P and calcitonin gene-related peptide decreased in the same region with both manipulations. The decrease in immunocytochemical levels of peptides is in agreement with previous observations and can result from activity-related depletion. We propose that the increase in glutamate levels reflects differences in the regulation and kinetics of amino acid versus peptide neuromediators.