Differential regulation of TRP channels in a rat model of neuropathic pain

Abstract

Neuropathic pain is a chronic disease resulting from dysfunction of the nervous system often due to peripheral nerve injury. Hypersensitivity to sensory stimuli (mechanical, thermal or chemical) is a common source of pain in patients and ion channels involved in detecting these stimuli are possible candidates for inducing and/or maintaining the pain. Transient receptor potential (TRP) channels expressed on nociceptors respond to different sensory stimuli and a few of them have been studied previously in the models of neuropathic pain. Using real-time PCR for quantification of all known TRP channels we identified several TRP channels, which have not been associated with nociception or neuropathic pain before, to be expressed in the DRG and to be differentially regulated after spared nerve injury (SNI). Of all TRP channel members, TRPML3 showed the most dramatic change in animals exhibiting neuropathic pain behaviour compared to control animals. In situ hybridisation showed a widespread increase of expression in neurons of small, medium and large cell sizes, indicating expression in multiple subtypes. Co-localisation of TRPML3 with CGRP, NF200 and IB4 staining confirmed a broad subtype distribution. Expression studies during development showed that TRPML3 is an embryonic channel that is induced upon nerve injury in three different nerve injury models investigated. Thus, the current results link for the first time a re-expression of TRPML3 with the development of neuropathic pain conditions. In addition, decreased mRNA levels after SNI were seen for TRPM6, TRPM8, TRPV1, TRPA1, TRPC3, TRPC4 and TRPC5.

Neuropathic Pain Following Nerve Injury

“…These observations point to different molecular mechanisms of heat hyperalgesia during inflammatory and neuropathic pain. The antinociceptive effect of TRPV1 antagonist further supports the idea of crucial role of TRPV1 in the development of neuropathic pain (Baron, 2000;Hudson et al, 2001;Staaf et al, 2009). …”

Epigenetic Gene Silencing Underlies C-Fiber Dysfunctions in Neuropathic Pain

“…The PCR primers used are listed in supplemental Table 1, available at www.jneurosci.org as supplemental material. Some of the primers were published previously (Koenigsberger et al, 2000;Klein et al, 2003;Qiang et al, 2005;Matsumoto et al, 2006;Cheng et al, 2009;Staaf et al, 2009). Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as an internal control for normalization.…”

Roles of TRPA1 in Pain Pathophysiology and Implications for the Development of a New Class of Analgesic Drugs

“…In mice, the expression was instead significantly reduced in DRGs at day 7 and 14, in agreement with a reduction in the number of AITC-sensitive cells [62]. In the rat spared nerve injury (SNI) model, the TRPA1 gene was down-regulated at 4 and 15 days post-surgery and returned to normal or above normal at 3 months [155]. In the mouse partial nerve injury model (Seltzer method), TRPA1 mRNA levels were strongly reduced in L4 and L5 DRGs at times where mechanical allodynia could be observed [155].…”