Effects of substance P on excitability and ionic currents of normal and axotomized rat dorsal root ganglion neurons

Substance P (SP) may act within dorsal root ganglia (DRG) to modulate the t ransmission of nociceptive information. Because peripheral nerve injury (ax otomy) alters the peptide content of sensory neurons, we used whole-cell re cording to examine the effects of sciatic nerve section on the sensitivity of rat lumbar DRG neurons to SP (0.3-1 muM). At 1 muM, SP increased the exc itability of 'small', putative nociceptive neurons but had little effect on the excitability of 'large' neurons. Two-four weeks after sciatic nerve se ction, however, the effect of SP on 'large' axotomized neurons was increase d and its effect on 'small' neurons was decreased. SP did not affect Ca2+ c hannel currents in control or axotomized neurons. The effects of SP on the current-voltage (I-V) relationship of 77% of neurons involved increased inw ard current at potentials below -30 mV and suppressed outward current at po tentials above -20 mV. The effects of SP on the I-V relationship were simil ar in control and in axotomized neurons and the altered sensitivity of 'sma ll' and 'large' cells could not be attributed to axotomy-induced changes in input resistance or membrane potential. The possible relevance of alterati ons in sensitivity, of 'large' DRG neurons to SP, to the generation of neur opathic pain is discussed.