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

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Abstract
Substance P (SP) may act within dorsal root ganglia (DRG) to modulate the transmission of nociceptive information. Because peripheral nerve injury (axotomy) alters the peptide content of sensory neurons, we used whole‐cell recording to examine the effects of sciatic nerve section on the sensitivity of rat lumbar DRG neurons to SP (0.3–1 µm). At 1 µm, SP increased the excitability of ‘small’, putative nociceptive neurons but had little effect on the excitability of ‘large’ neurons. Two‐four weeks after sciatic nerve section, however, the effect of SP on ‘large’ axotomized neurons was increased and its effect on ‘small’ neurons was decreased. SP did not affect Ca2+ channel currents in control or axotomized neurons. The effects of SP on the current‐voltage (I–V) relationship of 77% of neurons involved increased inward current at potentials below −30 mV and suppressed outward current at potentials above −20 mV. The effects of SP on the I–V relationship were similar in control and in axotomized neurons and the altered sensitivity of ‘small’ and ‘large’ cells could not be attributed to axotomy‐induced changes in input resistance or membrane potential. The possible relevance of alterations in sensitivity, of ‘large’ DRG neurons to SP, to the generation of neuropathic pain is discussed.