Nerve injury induces a new profile of tactile and mechanical nociceptor input from undamaged peripheral afferents

Abstract

Boada MD, Gutierrez S, Aschenbrenner CA, Houle TT, Hayashida K, Ririe DG, Eisenach JC. Nerve injury induces a new profile of tactile and mechanical nociceptor input from undamaged peripheral afferents. J Neurophysiol 113: 100 -109, 2015. First published October 1, 2014 doi:10.1152/jn.00506.2014.-Chronic pain after nerve injury is often accompanied by hypersensitivity to mechanical stimuli, yet whether this reflects altered input, altered processing, or both remains unclear. Spinal nerve ligation or transection results in hypersensitivity to mechanical stimuli in skin innervated by adjacent dorsal root ganglia, but no previous study has quantified the changes in receptive field properties of these neurons in vivo. To address this, we recorded intracellularly from L 4 dorsal root ganglion neurons of anesthetized young adult rats, 1 wk after L 5 partial spinal nerve ligation (pSNL) or sham surgery. One week after pSNL, hindpaw mechanical withdrawal threshold in awake, freely behaving animals was decreased in the L 4 distribution on the nerve-injured side compared with sham controls. Electrophysiology revealed that highthreshold mechanoreceptive cells of A-fiber conduction velocity in L 4 were sensitized, with a seven-fold reduction in mechanical threshold, a seven-fold increase in receptive field area, and doubling of maximum instantaneous frequency in response to peripheral stimuli, accompanied by reductions in after-hyperpolarization amplitude and duration. Only a reduction in mechanical threshold (minimum von Frey hair producing neuronal activity) was observed in C-fiber conduction velocity high-threshold mechanoreceptive cells. In contrast, low-threshold mechanoreceptive cells were desensitized, with a 13-fold increase in mechanical threshold, a 60% reduction in receptive field area, and a 40% reduction in instantaneous frequency to stimulation. No spontaneous activity was observed in L 4 ganglia, and the likelihood of recording from neurons without a mechanical receptive field was increased after pSNL. These data suggest massively altered input from undamaged sensory afferents innervating areas of hypersensitivity after nerve injury, with reduced tactile and increased nociceptive afferent response. These findings differ importantly from previous preclinical studies, but are consistent with clinical findings in most patients with chronic neuropathic pain. chronic pain model; in vivo electrophysiology; sensory neurons; spinal nerve ligation IN HUMANS, NEUROPATHIC PAIN includes both spontaneous and evoked pain, often accompanied by hypersensitivity to normal nociceptive stimuli (hyperalgesia) and normally nonnociceptive stimuli (allodynia). This pathological condition is also sometimes accompanied by dysesthesias and paresthesias (von Hehn et al. 2012), suggesting that both tactile and nociceptive information channels and/or processing are disrupted.

The diagnosis and management of nerve injury during endodontic treatment

“…The clinical neurosensory testing may be divided into two types: mechanoceptive and nociceptive (Boada et al, 2015), based on the specific stimulated receptors being evaluated (Rosen, 2014;Juodzbalys et al, 2011;Ghali & Epker, 1989;Boada et al, 2015). Mechanoceptive testing includes clinical tests such as the 'Static light touch' test or the "Two-point discrimination" test (Ghali & Epker, 1989).…”

Mechanical sensibility of nociceptive and non-nociceptive fast-conducting afferents is modulated by skin temperature

“…The procedure used in this study to classify primary sensory afferents in vivo has been described in detail (Boada et al 2015). Briefly, RFs were located with the aid of a stereomicroscope using increasing mechanical stimulation; the latter progressed from light touch with a fine sable hair paintbrush to searching with blunt probes and ultimately gentle to noxious pinch with fine-tipped forceps.…”

A pharmacological and transcriptomic approach to exploring novel pain targets

“…Afibre block in capsaicin-induced pain resulted in a 75% reduction of mechanical allodynia, but retained the burning sensation felt from capsaicin 22,23 . At the same time, spinal nerve ligation in rats resulted in increased excitability of mechano-sensitive A-fibres, as well as an increase in the size of these fibres' receptive fields and maximum firing frequency 24 . Such findings have led towards the preposition that A-fibres contribute more towards mechanical allodynia, while C-fibres are responsible for thermal hyperalgesia.…”

“…A-fibre block also did not affect long-term potentiation following high frequency electrical stimulation 20 . Spinal nerve ligation in rats caused a reduction in the mechanical threshold of high-threshold mechano-sensitive A-fibres, in addition to an increase in the area of A-fibres' receptive fields and an increase in maximum instantaneous frequency 24 . In the same spinal nerve ligation model, however, the high-threshold mechano-sensitive C-fibres only exhibited a reduction in mechanical threshold 24 .…”

“…Spinal nerve ligation in rats caused a reduction in the mechanical threshold of high-threshold mechano-sensitive A-fibres, in addition to an increase in the area of A-fibres' receptive fields and an increase in maximum instantaneous frequency 24 . In the same spinal nerve ligation model, however, the high-threshold mechano-sensitive C-fibres only exhibited a reduction in mechanical threshold 24 . This has led to the conclusion that Cnociceptors predominantly mediate thermal hyperalgesia and allodynuia, whereas mechanical hypersensitivity is mediated by A-fibres instead 25,26 .…”