Substance P in human cerebrospinal fluid: reductions in peripheral neuropathy and autonomic dysfunction

Substance P (SP), a putative peptide neurotransmitter, was measured in human lumbar cerebrospinal fluid (CSF) by radioimmunoassay. Substance P-like immunoreactivity (SPLI) was present in the CSF of 18 neurologically normal adults in concentrations ranging from 2.9 to 11.1 fmol per milliliter, with a mean of 7.0 /+- 0.6 fmol per milliliter (mean /+- SE). Slightly more than half of the CSF-SPLI cochromatographed with synthetic SP on Sephadex G-25. There was no apparent gradient in CSF-SPLI concentration over the first 30 ml of CSF removed by lumbar puncture. Mean concentrations CSF-SPLI in patients with Huntington disease, parkinsonism, miscellaneous dyskinesias, progressive supranuclear palsy, myopathy, and amyotrophic lateral sclerosis did not differ significantly from normal. Patients with neuropathy or multiple-system atrophy (Shy-Drager syndrome) had significantly reduced mean CSF-SPLI concentrations. These observations suggest that lumbar CSF-SPLI arises largely from spinal cord, nerve roots, or dorsal root ganglia, and that pathologic processes affecting these structures may be reflected by reduced levels of CSF-SPLI.