The origin of the excitatory amino acids (EAA) aspartate (Asp) and glutamate (Glu) released into the dorsal spinal cord extracellular fluid of rats following intradialysate infusion of substance P (SP) was studied using neonatal capsaicin, dorsal rhizotomy and proximal spinal cord transection. Neonatal capsaicin (50 mg/kg i.p.) had no effect on basal EAA release, but significantly inhibited SP-induced release of both Asp (86%) and Glu (70%). Bilateral dorsal rhizotomy enhanced SP-induced release of Asp (152%) and had no effect on Glu release compared to sham-operated controls. Proximal spinal transection (T8-9) had no effect on basal or SP-induced release of EAAs compared to sham-operated controls. The ability of neonatal capsaicin to inhibit, and dorsal rhizotomy to potentiate Asp release correlates well with their distinct effects on hyperalgesia and suggests that these manipulations do not produce identical lesions. Neonatal capsacin likely interferes with the normal development of EAA interneurons innervated by SP primary afferent C-fibers. Rhizotomy may result in a compensatory up-regulation of SP receptors on EAA interneurons.
Bibliographical noteFunding Information:
The authors would like to express their sincere appreciation to Dr. David Smullin and Paul Staab for their assistance in conducting these studies and Dr. Darrell Mousseau for editorial comments. This work was supported by U.S. Public Health Service Grants (DA04090, DA04190, DA00124) to A.A.L. and (CA01342) to S.R.S. The use and care of animals in this study were performed in accordance with the guidelines of the Minnesota Animal Care and Use Committee and those prepared by the Committee on Care and Use of Laboratory Animals of the Institute of Laboratory Animal Resources, National Research Council (DHEW publication (NIH) 78-23, revised 1978).
- Spinal transection