Abstract
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.
Original language | English |
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Pages (from-to) | 1824-1836 |
Number of pages | 13 |
Journal | PAIN |
Volume | 153 |
Issue number | 9 |
DOIs | |
Publication status | Published - Sept 2012 |
Keywords
- Uninjured neuron
- Spontaneous firing
- Dorsal root ganglion
- Nociceptor
- Pain behaviour
- Nerve injury
- Nociception
- Neuropathic pain
- Threshold
- Allodynia
- Hyperalgesia
- Neuroinflammation
- Spontaneous pain
- Paresthesia
- Action potential
- Membrane potential
- In vivo
- Intracellular recording
- A beta-nociceptors
- A-fibre nociceptors
- C-fibre nociceptors
- Low-threshold mechanoreceptors
- DORSAL-ROOT GANGLION
- PRIMARY AFFERENT NEURONS
- PRIMARY SENSORY NEURONS
- ACTION-POTENTIAL SHAPE
- GUINEA-PIG
- SODIUM-CHANNELS
- IN-VIVO
- MEMBRANE-PROPERTIES
- INFLAMMATORY PAIN
- TACTILE ALLODYNIA