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.
Highlights
Neuropathic pain of peripheral origin (NP) often results from partial injury of a peripheral nerve resulting in dorsal root⇑ Corresponding author
This study provides novel information about electrophysiological/membrane changes in different subgroups of L4 receptive fields (RFs)-neurons in vivo that are likely to result in increased central nervous system (CNS) input and contribute to pathological pain or altered sensation
To explore possible mechanisms underlying these behavioural changes, we examined the electrophysiological properties of L4/ L5 DRG neurons in normal and L4 RF-neurons in spinal nerve axotomy (SNA) and modified SNA (mSNA) rats
Summary
Mechanisms of increased afferent input in NP include increased SF, and decreased thresholds, resulting in greater firing to noxious or innocuous stimuli in neurons with uninterrupted/conducting fibres, but the full extent of changes in these DRG neurons after partial nerve injury is unknown. We made intracellular recordings in vivo in normal L4/L5 DRG neurons in normal (untreated) rats and in L4 DRG RF-neurons in 2 rat models of NP These were L5 spinal nerve axotomy (SNA), and modified SNA (mSNA) with additional loose ligature of the L4 spinal nerve with chromic gut, which induces neuroinflammation [54,68]. This study provides novel information about electrophysiological/membrane changes in different subgroups of L4 RF-neurons in vivo that are likely to result in increased CNS input and contribute to pathological pain or altered sensation.
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