L5 spinal nerve axotomy induces sensitization of cutaneous L4 Aβ-nociceptive dorsal root ganglion neurons in the rat in vivo

Partial nerve injury often leads to peripheral neuropathic pain (PNP), a major health problem that lacks effective drug treatment. PNP is characterized by ongoing/spontaneous pain, and hypersensitivity to noxious (hyperalgesia) and innocuous (allodynia) stimuli. Preclinical studies using the L5 spinal nerve ligation/axotomy (SNL/SNA) model of PNP suggest that this type of chronic pain results partly from sensitization of ipsilateral L4C-and A delta-fiber nociceptive dorsal root ganglion (DRG) neurons, but whether L4 beta-nociceptors, which constitute a substantial group of DRG neurons, also become sensitized remains unanswered. To address this issue, intracellular recordings from somata of cutaneous A beta-nociceptors (classified according to their dorsal root conduction velocities (>6.5 m/s), and physiologically based on their responses to noxious (but not innocuous) mechanical stimuli) were made from L4-DRGs in normal (control) rats and in rats seven days after L5 SNA in vivo. Compared with control, cutaneous L4 A beta-nociceptive DRG neurons in SNA rats (that developed mechanical hypersensitivity) exhibited sensitization indicated by: a) decreased mean mechanical threshold (from 57.8 +/- 7.1 to 10.3 +/- 1.7 mN), b) decreased mean dorsal root electrical threshold (from 11.4 +/- 0.7 to 4.3 +/- 0.4 V), c) increased mean response to a suprathreshold mechanical stimulus (from 18.5 +/- 1.8 to 34 +/- 3.7 spikes/sec) and d) an obvious, but non-significant, increase in the incidence of ongoing/spontaneous activity (from 3% to 18%). These findings suggest that cutaneous L4 A beta-nociceptors also become sensitized after L5 SNA, and that sensitization of this subclass of A-fiber nociceptors may contribute both directly and indirectly to nerve injury-induced PNP. (C) 2016 Elsevier Ireland Ltd. All rights reserved.