ErbB4 in Spinal PV Interneurons Regulates Mechanical Allodynia in Neuropathic Pain via Modulation of Glycinergic Inhibitory Tone

Abstract

Background: Mechanical allodynia is the most common and challenging symptom associated with neuropathic pain; however, the underlying mechanisms are still unclear. The aim of this study was to investigate whether ErbB4, a receptor for neuregulin-1 (NRG1), participates in the modulation of mechanical allodynia. Methods: Radiant heat and von Frey filaments were applied to assess nociceptive behaviors. Real-time quantitative polymerase chain reaction, Western blotting, immunofluorescence, and small interfering RNA were used to identify the likely mechanisms. Results: ErbB4 was rapidly and persistently activated in spinal parvalbumin (PV) interneurons after chronic constriction injury (CCI) in mice. Knockdown of ErbB4 in the spinal cord prevented and reversed CCI-induced mechanical allodynia, and activation of ErbB4 by spinal application of NRG1 induced mechanical allodynia in naïve mice. Furthermore, we found that activation of ErbB4 decreased the glycine concentration in the spinal cord, contributing to modulation of mechanical allodynia. Conclusion: ErbB4 in spinal PV interneurons gates mechanical allodynia in neuropathic pain via regulation of glycinergic inhibitory tone, suggesting that a possible ErbB4-mediated process participates in the development of neuropathic pain.

Increased Brain-Derived Neurotrophic Factor Levels in Cerebrospinal Fluid During the Acute Phase in TBI-Induced Mechanical Allodynia in the Rat Model

“…Neuropathic pain is defined as pain caused by a lesion or disease of the somatosensory system, and the somatosensory system allows for the perception of touch, pressure, pain, temperature, position, movement, and vibration. 37 Although mechanical allodynia is the most common symptom of neuropathic pain, 38 this study is insufficient to represent neuropathic pain that comprises a wide range of heterogeneous conditions. 39 To date, there is no single behavioral assay capable of capturing the full spectrum of nociception in animal subjects.…”

The therapeutic effects of transferring remote ischemic preconditioning serum in rats with neuropathic pain symptoms

“…In addition, slower absorption and lower peak plasma concentrations may occur with intraperitoneal and subcutaneous administration [ 27 ]. The mechanisms contributing to thermal hyperalgesia and mechanical allodynia differ are different [ [28] , [29] , [30] ]. In the PSNL model, blockade of TRPV1 channels in the dorsal horn of the spinal cord for five days was shown to play a role in the development of thermal hyperalgesia but not mechanical allodynia [ 29 ].…”