期刊
PAIN
卷 153, 期 9, 页码 1824-1836出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1016/j.pain.2012.04.019
关键词
Uninjured neuron; Spontaneous firing; Dorsal root ganglion; Nociceptor; Pain behaviour; Nerve injury; Nociception; Neuropathic pain; Threshold; Allodynia; Hyperalgesia; Neuroinflammation; Spontaneous pain; Allodynia; Hyperalgesia; Paresthesia; Action potential; Membrane potential; In vivo; Intracellular recording; A beta-nociceptors; A-fibre nociceptors; C-fibre nociceptors; Low-threshold mechanoreceptors
资金
- Wellcome Trust, UK
- MRC
- University of Bristol
- Medical Research Council [G0700420] Funding Source: researchfish
- MRC [G0700420] Funding Source: UKRI
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 heat-hypersensitivity/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-, Ad-, and Ab-nociceptors and cutaneous Aa/b-low-threshold mechanoreceptors with ongoing/spontaneous firing; b) spontaneous firing in C-nociceptors that originated peripherally; this was at a faster rate in modified-SNA than SNA; c) decreased electrical thresholds in A-nociceptors after SNA; d) hyperpolarised membrane potentials in A-nociceptors and Aa/b-low-threshold-mechanoreceptors after SNA, but not C-nociceptors; e) decreased somatic action potential rise times in C- and A-nociceptors, not Aa/b-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 Aa/b-low-threshold-mechanoreceptors to dysesthesias/paresthesias; and lowered A-nociceptor electrical thresholds to A-nociceptor sensitization, and greater evoked pain. (C) 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
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