No requirement of TRPV1 in long-term potentiation or long-term depression in the anterior cingulate cortex

Ming-Gang Liu,Min Zhuo

doi:10.1186/1756-6606-7-27

Abstract

One major interest in the study of transient receptor potential vanilloid type 1 (TRPV1) in sensory system is that it may serve as a drug target for treating chronic pain. While the roles of TRPV1 in peripheral nociception and sensitization have been well documented, less is known about its contribution to pain-related cortical plasticity. Here, we used 64 multi-electrode array recording to examine the potential role of TRPV1 in two major forms of synaptic plasticity, long-term potentiation (LTP) and long-term depression (LTD), in the anterior cingulate cortex (ACC). We found that pharmacological blockade of TRPV1 with either [(E)-3-(4-t-Butylphenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acrylamide] (AMG9810, 10 μM) or N-(3-methoxyphenyl)-4-chlorocinnamide (SB366791, 20 μM) failed to affect LTP induced by strong theta burst stimulation in the ACC of adult mice. Similarly, neither AMG9810 nor SB366791 blocked the cingulate LTD induced by low-frequency stimulation. Analysis of the results from different layers of the ACC obtained the same conclusions. Spatial distribution of LTP or LTD-showing channels among the ACC network was also unaltered by the TRPV1 antagonists. Since cortical LTP and LTD in the ACC play critical roles in chronic pain triggered by inflammation or nerve injury, our findings suggest that TRPV1 may not be a viable target for treating chronic pain, especially at the cortical level.

Highlights

The transient receptor potential vanilloid type 1 (TRPV1) is known to act as a molecular detector for a wide range of physical (>42°C temperature) and chemical stimuli in the periphery [1,2,3,4]
Neurophysiological and pharmacological studies demonstrate that TRPV1 is important for certain forms of synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD), in different central synapses [20, see Table 2]
Pharmacological blockade of TRPV1 with AMG9810 does not affect LTP induction in the anterior cingulate cortex (ACC) The important role of TRPV1 in LTP induction in the hippocampus has been shown in previous work using the genetically modified mice [21,22,23]

Summary

Introduction

The transient receptor potential vanilloid type 1 (TRPV1) is known to act as a molecular detector for a wide range of physical (>42°C temperature) and chemical (low PH, capsaicin) stimuli in the periphery [1,2,3,4]. Pharmacological blockade or genetic deletion of TRPV1 channel can produce significant analgesic effects in acute pain as well as inflammatory pain [5,6,7,8,9]. Neurophysiological and pharmacological studies demonstrate that TRPV1 is important for certain forms of synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD), in different central synapses [20, see Table 2]. LTP in the hippocampus is impaired in the TRPV1-deficient mice [21,22,23]. TRPV1 receptors can mediate a presynaptic form of LTD in the hippocampus [24] and a postsynaptic form of LTD in the dentate gyrus [25] and nucleus accumbens [26]

Methods

Results

Conclusion