Inhibition of Spinal TRPV1 Reduces NMDA Receptor 2B Phosphorylation and Produces Anti-Nociceptive Effects in Mice with Inflammatory Pain.

Suk-Yun Kang,Seong Jin Cho,Su Yeon Seo,Se Kyun Bang,Yeonhee Ryu,Kwang-Ho Choi

doi:10.3390/ijms222011177

Abstract

Transient receptor potential vanilloid 1 (TRPV1) has been implicated in peripheral inflammation and is a mediator of the inflammatory response to various noxious stimuli. However, the interaction between TRPV1 and N-methyl-D-aspartate (NMDA) receptors in the regulation of inflammatory pain remains poorly understood. This study aimed to investigate the analgesic effects of intrathecal administration of capsazepine, a TRPV1 antagonist, on carrageenan-induced inflammatory pain in mice and to identify its interactions with NMDA receptors. Inflammatory pain was induced by intraplantar injection of 2% carrageenan in male ICR mice. To investigate the analgesic effects of capsazepine, pain-related behaviors were evaluated using von Frey filaments and a thermal stimulator placed on the hind paw. TRPV1 expression and NMDA receptor phosphorylation in the spinal cord and glutamate concentration in the spinal cord and serum were measured. Intrathecal treatment with capsazepine significantly attenuated carrageenan-induced mechanical allodynia and thermal hyperalgesia. Moreover, carrageenan-enhanced glutamate and phosphorylation of NMDA receptor subunit 2B in the spinal cord were suppressed by capsazepine administration. These results indicate that TRPV1 and NMDA receptors in the spinal cord are associated with inflammatory pain transmission, and inhibition of TRPV1 may reduce inflammatory pain via NMDA receptors.

Highlights

The transient receptor potential (TRP) family is one of the most important and wellstudied groups of ion channels involved in biological processes
We investigated the effects of intrathecal administration of the Transient receptor potential vanilloid 1 (TRPV1) antagonist, capsazepine, on carrageenan-induced inflammatory pain responses, such as mechanical allodynia and thermal hyperalgesia, in mice
In the ipsilateral hind paws, the carrageenan injection group (2% CR) exhibited increased paw withdrawal frequency (%) compared to control animals (Control) from 1 to 24 h after carrageenan administration (*** p < 0.001), whereas no significant difference was observed in paw withdrawal frequency (%) between saline-treated animals (Vehicle) and control animals from 1 h after carrageenan administration to the final behavioral measurement at 24 h (Figure 1A)

Summary

Introduction

The transient receptor potential (TRP) family is one of the most important and wellstudied groups of ion channels involved in biological processes. TRP channels are a group of ion channels located predominantly on the plasma membrane of cells. These channels mediate a variety of sensations such as temperature, touch, osmolarity, and chemicals that cause painful sensations [1]. Activation of TRP channels enables crosstalk between neurons and immune cells to regulate inflammatory processes and permits detection of noxious stimuli by triggering action potentials in peripheral nociceptors [2,3]. TRPV1 plays a major role in sensing noxious heat stimuli and mediating thermal hyperalgesia in inflammation [4]. Due to its role as a regulator of inflammatory pain, TRPV1 is a promising target for therapeutic intervention in the management of inflammatory pain

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