Reversibility and prevention of intraspinal peptidergic loss caused by sciatic nerve lesions.

We have investigated the reversibility and prevention of peptidergic losses in the lumbar spinal cord caused by permanent resection of sciatic nerve. The lesion triggers a series of degenerative events involving the substance P sensory imput as well as met-enkephalin interneurons of the substantia gelatinosa. The degenerative processes are evident 10 days after sciatic nerve lesion and are gradually reversible as shown by radioimmunoassay and quantitative immunocytochemistry. Recovery begins 30 days postlesioning and full restoration is observed at 90 days. Serotonin (5-HT) turnover is markedly affected by sciatic nerve lesion as soon as 24 hr postlesioning, when 5-HT metabolism is enhanced, returning to control levels just preceding the peptide alterations; 5-HT metabolism then undergoes a transient period of hypoactivity which correlates with the beginning of the peptidergic restorative processes. Altogether these results, with previous observations showing that 5-HT depletion prevents metenkephalin interneurons degeneration triggered by the lesion (Di Giulio et al.: J Neurosci Res 18:443-448, 1987), suggest a role for 5-HT in the synaptic plasticity of the substantia gelatinosa of the spinal cord. The administration of gangliosides (10 or 50 mg/kg) to sciatic-nerve-lesioned animals fully prevented the metenkephalinergic degeneration without affecting the degenerative atrophy of the lesioned substance P sensory imput.