Effect of TRPV4-p38 MAPK Pathway on Neuropathic Pain in Rats with Chronic Compression of the Dorsal Root Ganglion.

Yu-Juan Qu,Shou-Wei Yue,Yong-Bo Teng,Zhen-Zhen Fan,Yang Zhang,Juan Huai,Xiao Zhang

doi:10.1155/2016/6978923

Abstract

The aim of this study was to investigate the relationships among TRPV4, p38, and neuropathic pain in a rat model of chronic compression of the dorsal root ganglion. Mechanical allodynia appeared after CCD surgery, enhanced via the intrathecal injection of 4α-phorbol 12,13-didecanoate (4α-PDD, an agonist of TRPV4) and anisomycin (an agonist of p38), but was suppressed by Ruthenium Red (RR, an inhibitor of TRPV4) and SB203580 (an inhibitor of p38). The protein expressions of p38 and P-p38 were upregulated by 4α-PDD and anisomycin injection but reduced by RR and SB203580. Moreover, TRPV4 was upregulated by 4α-PDD and SB203580 and downregulated by RR and anisomycin. In DRG tissues, the numbers of TRPV4- or p38-positive small neurons were significantly changed in CCD rats, increased by the agonists, and decreased by the inhibitors. The amplitudes of ectopic discharges were increased by 4α-PDD and anisomycin but decreased by RR and SB203580. Collectively, these results support the link between TRPV4 and p38 and their intermediary role for neuropathic pain in rats with chronic compression of the dorsal root ganglion.

Highlights

After tissue injury and inflammation, the sensory signals from the primary sensory neurons to the spinal dorsal horn change significantly, leading to the development of chronic pain [1]
paw withdrawal mechanical threshold (PWMT) significantly decreased from the second day after chronic compression of the DRGs (CCD) surgery, lasting 14 days (P < 0.01, Figure 1); it increased to normal levels
To study the effects of TRP vanilloid receptor 4 (TRPV4) and p38 with regard to neuropathic pain further, we sought to determine the abilities of RR, 4α-PDD, SB203580, and anisomycin to enhance or block the nociception signs induced 4 days after CCD surgery

Summary

Introduction

After tissue injury and inflammation, the sensory signals from the primary sensory neurons to the spinal dorsal horn change significantly, leading to the development of chronic pain [1]. Radicular neuralgia is the most common form of neuropathic pain; it occurs when the radix spinalis or the dorsal root ganglia (DRGs) are stimulated by harmful factors (e.g., the protrusion of a lumbar intervertebral disc, lumbar spinal stenosis, spinal cord tumor compression, and certain inflammatory substances). They become excited to create and transmit neuropathic pain signals [4]. Our studies have used chronic compression of the DRGs (CCD) as a typical model of neuropathic pain that demonstrates spontaneous pain, hyperalgesia, and allodynia and is accompanied by increased spontaneous discharges of neurons as well as decreased action potentials and electric current thresholds [5]

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