Depletion of substance P-containing axons in substantia gelatinosa of patients with diminished pain sensitivity.

Abstract

Substance P is an undecapeptide which may be involved in transmission of nociceptive information at synapses of primary sensory neurones1,2. It occurs in 10–20% of rat dorsal root ganglion neurones3,4. Small substance P-immunoreactive (SP-IR) axons from dorsal root ganglia enter the spinal cord and form a dense terminal network in the substantia gelatinosa of the rat dorsal horn3; analogous fibres from the trigeminal ganglion terminate in the substantia gelatinosa of the spinal trigeminal tract of the medulla oblongata4,5, while sensory axons travelling via the petrosal and nodose ganglia terminate in the tractus solitarius of the medulla5–8. Substance P is also present in human spinal cord and pallido-nigral system9–12. In addition to sympathetic and parasympathetic abnormalities, patients with familial dysautonomia (the Riley–Day syndrome) have severe diminution of temperature and pain sensitivity, reduced populations of primary sensory neurones and small Lissauer's tracts13. It was thus postulated that a diminution of primary substance P axons might be demonstrable using immunocytochemistry. We report here the presence of anatomically discrete depletion of substance P immunoreactivity in the substantia gelatinosa of spinal cord and medulla of patients with familial dysautonomia. The results are consistent with the hypothesis that substance P is involved in the transmission of impulses related to pain.