Partial nerve injury induces electrophysiological changes in conducting (uninjured) nociceptive and nonnociceptive DRG neurons: Possible relationships to aspects of peripheral neuropathic pain and paresthesias.
Partial nerve injury leads to peripheral neuropathic pain. This injury results in conducting/uninterrupted (also called uninjured)sensory fibres, conducting through the damaged nerve alongside axotomised/degenerating fibres. In rats seven days after L5 spinal nerve axotomy (SNA) or modified-SNA (added loose-ligation of L4 spinal nerve with neuroinflammation-inducing chromic-gut),we investigated (a) neuropathic pain behaviours and (b) electrophysiological changes in conducting/uninterrupted L4 dorsal root ganglion (DRG) neurons with receptive fields (called: L4-receptive-field-neurons). Compared to pretreatment, modified-SNA rats showed highly significant increases in spontaneous-foot lifting duration, mechanical-hypersensitivity/allodynia, and heathypersensitivity/hyperalgesia, that were significantly greater than after SNA, especially spontaneous-foot-lifting. We recorded intracellularly in vivo from normal L4/L5 DRG neurons and ipsilateral L4-receptive-field-neurons. After SNA or modified-SNA, L4-receptive-field-neurons showed the following: (a) increased percentages of C-, Aδ-, and Aβ-nociceptors and cutaneous Aα/β-low-thresholdmechanoreceptors with ongoing/spontaneous firing; (b) spontaneous firing in C-nociceptors that originated peripherally; this was ata faster rate in modified-SNA than SNA; (c) decreased electricalthresholds in A-nociceptors after SNA; (d) hyperpolarised membrane potentials in A-nociceptors and Aα/-low-thresholdmechanoreceptors after SNA, but not C-nociceptors; (e) decreased somatic action potential rise times in C- and A-nociceptors, not Aα/β-low-threshold-mechanoreceptors. We suggest that these changes in subtypes of conducting/uninterrupted neurons after partial nerve injury contribute to the different aspects of neuropathic pain as follows: spontaneous firing in nociceptors to ongoing/spontaneous pain; spontaneous firing in Aα/β-low-threshold-mechanoreceptors to dysesthesias/paresthesias; and lowered A-nociceptor electrical thresholds to A-nociceptor sensitization,and greater evoked pain [corrected].
School of Physiology and Pharmacology, University of Bristol, Bristol BS8 1TD, UK.
Laiche
L
Djouhri
Xin
X
Fang
Stella
S
Koutsikou
Sally N
SN
Lawson
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D019771:Axotomy; D001522:Behavior, Animal; D005260:Female; D005727:Ganglia, Spinal / Q000503:physiopathology*; D006358:Hot Temperature; D006930:Hyperalgesia / Q000503:physiopathology; D008465:Mechanoreceptors / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D009437:Neuralgia / Q000503:physiopathology*; D009619:Nociceptors / Q000502:physiology*; D010292:Paresthesia / Q000503:physiopathology; D059348:Peripheral Nerve Injuries / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D013127:Spinal Nerves / Q000293:injuries / Q000502:physiology* / Q000503:physiopathology; D014110:Touch