Chronic pain induces generalized enhancement of aversion.

Qiaosheng Zhang,Jing Wang,Louise Urien,Toby Manders,Arpan Garg,Abhinav Goyal,Haocheng Zhou,Erik Martinez,Runtao Yang,Guang Yang,Jahrane Dale,Ai Phuong Tong,Zhe Chen

doi:10.7554/elife.25302

Abstract

A hallmark feature of chronic pain is its ability to impact other sensory and affective experiences. It is notably associated with hypersensitivity at the site of tissue injury. It is less clear, however, if chronic pain can also induce a generalized site-nonspecific enhancement in the aversive response to nociceptive inputs. Here, we showed that chronic pain in one limb in rats increased the aversive response to acute pain stimuli in the opposite limb, as assessed by conditioned place aversion. Interestingly, neural activities in the anterior cingulate cortex (ACC) correlated with noxious intensities, and optogenetic modulation of ACC neurons showed bidirectional control of the aversive response to acute pain. Chronic pain, however, altered acute pain intensity representation in the ACC to increase the aversive response to noxious stimuli at anatomically unrelated sites. Thus, chronic pain can disrupt cortical circuitry to enhance the aversive experience in a generalized anatomically nonspecific manner.

Highlights

Chronic pain exerts a profound influence over daily life by impacting a range of sensory and affective behaviors
We found that anterior cingulate cortex (ACC) activation during the presentation of Low-intensity noxious stimulus (LS) increased the aversive response to LS, as shown by an avoidance of the chamber associated with optogenetic activation during the test phase compared with baseline (Figure 3D)
We found that ACC inhibition decreased the aversive response to LS and high-intensity noxious (HS), as shown by increased amounts of time spent in the chamber associated with LS or HS coupled with ACC inhibition during the test phase compared with baseline (Figure 4C,D)

Summary

Introduction

Chronic pain exerts a profound influence over daily life by impacting a range of sensory and affective behaviors. It is associated with enhanced response to noxious stimuli, leading to symptoms of allodynia and hyperalgesia at the site of tissue or nerve injury (Basbaum et al, 2009; Latremoliere and Woolf, 2009) The mechanisms for such sensory and affective hypersensitivity at the site of chronic pain have been well investigated. Conditions such as fibromyalgia and persistent postoperative pain raise the possibility that chronic pain may increase the aversive reaction towards noxious stimuli in an anatomically nonspecific distribution (Scudds et al, 1987; Petzke et al, 2003; Kehlet et al, 2006; Kudel et al, 2007; Scott et al, 2010). While previous studies have demonstrated that the ACC is necessary

Methods

Results

Conclusion