INFLAMMATORY PAIN HYPERSENSITIVITY MEDIATED BY PHENOTYPIC SWITCH IN MYELINATED PRIMARY SENSORY NEURONS

PAIN is normally evoked only by stimuli that are sufficiently intense to activate high-threshold A delta and C sensory fibres, which relay t he signal tp the spinal cord, Peripheral inflammation leads to profoun dly increased pain sensitivity: noxious stimuli generate a greater res ponse and stimuli that are normally innocuous Elicit pain. Inflammatio n increases the sensitivity of the peripheral terminals of A delta and C fibres at the site of inflammation(1). It also increases the excita bility of spinal cord neurons(2,3), which now amplify all sensory inpu ts including the normally innocuous tactile stimuli that are conveyed by low-threshold A beta fibres. This central sensitization has been at tributed to the enhanced activity of C fibers(4), which increase the e xcitability of their postsynaptic targets by releasing glutamate and t he neuropeptide substance P5-7. Here we show that inflammation results in A beta fibres also acquiring the capacity to increase the excitabi lity of spinal cord neurons. This is due fa a phenotypic switch in a s ubpopulation of these fibres so that they, like C-fibres, now express substance P. A beta fibres thus appear to contribute to inflammatory h ypersensitivity by switching their phenotype to one resembling pain fi bres, thereby enhancing synaptic transmission in the spinal cord and e xaggerating the central response to innocuous stimuli.