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 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 microM). At 1 microM, 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 Ca(2+) 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.
Abdulla
F A
FA
Department of Physical Therapy, School of Allied Health Professions, Tennessee State University, Nashville, Tennessee 37209, USA.
Stebbing
M J
MJ
Smith
P A
PA
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D019771:Axotomy; D001464:Barium / Q000493:pharmacokinetics; D002118:Calcium / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology*; D008297:Male; D009437:Neuralgia / Q000378:metabolism / Q000503:physiopathology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries / Q000378:metabolism / Q000503:physiopathology; D013373:Substance P / Q000494:pharmacology*
D015221:Potassium Channels; D001464:Barium; D013373:Substance P; D019204:GTP-Binding Proteins; D002118:Calcium