Abnormal substance P release from the spinal cord following injury to primary sensory neurons

The neuropeptide substance P (SP) modulates nociceptive transmission within the spinal cord. Normally, SP is uniquely contained in a subpopulation of small-calibre axons (A delta- and C-fibres) within primary afferent nerve. However, it has been shown that after nerve transection, besides being down regulated in small axons, SR is expressed de novo in large myelinated AP-fi bres, In this study we investigated whether, following peripheral nerve inj ury, SP was released de novo from the spinal cord after selective activatio n of A beta-fibres, Spinal cords with dorsal roots attached were isolated i n vitro from rats 2 weeks following distal sciatic axotomy or proximal spin al nerve lesion (SNL). The ipsilateral dorsal roots were electrically stimu lated for two consecutive periods at low- or high-threshold fibre strength, spinal cord superfusates were collected and SP content was determined by r adioimmunoassay, SNL, but not axotomized or control rat cords, released sig nificant amounts of SP after selective activation of A beta-fibres. Not onl y do these data support the idea that A beta myelinated fibres contribute t o neuropathic pain by releasing SR, they also illustrate the importance of the proximity of the lesion to the cell body.