Abstract
Anxiety is a common comorbidity associated with chronic pain, which results in chronic pain complexification and difficulty in treatment. Electroacupuncture (EA) is commonly used to treat chronic pain and anxiety. However, the underlying mechanisms of the EA effect are largely unknown. Here, we showed that a circuitry underlying chronic pain induces anxiety disorders, and EA can treat them by regulating such circuitry. Using chemogenetic methods, we found that chemogenetic activation of the rostral anterior cingulate cortex (rACC) glutamatergic output to the thalamus induced anxiety disorders in control rats. Then, chemogenetic inhibition of the rACC-thalamus circuitry reduced anxiety-like behavior produced by intraplantar injection of the complete Freund’s adjuvant (CFA). In this study, we examined the effects of EA on a rat model of CFA-mediated anxiety-like behaviors and the related mechanisms. We found that chemogenetic activation of the rACC-thalamus circuitry effectively blocked the effects of EA on chronic pain-induced anxiety-like behaviors in CFA rats. These results demonstrate an underlying rACC-thalamus glutamatergic circuitry that regulates CFA-mediated anxiety-like behaviors. This study also provides a potential mechanistic explanation for EA treatment of anxiety caused by chronic pain.
Highlights
The International Association for the Study of Pain (IASP) defines pain as an unpleasant sensory and emotional experience associated with actual or potential tissue damage (Bushnell et al, 2013; Aydede, 2019; Meda et al, 2019)
To identify the possible inferior brain regions connected to the rostral anterior cingulate cortex (rACC) that could be involved in pain-induced anxiety, we first investigated the distribution of the mCherry signal after rACC infusion of rAAV2/9-CaMKIIα-mCherry in SD rats (Figures 2A,B)
Since activation of the rACC-thalamus circuitry in control rats induced anxiety, we investigated whether the inhibition of the excitability of the rACC-projecting thalamic neurons suppressed pain-induced anxiety disorders
Summary
The International Association for the Study of Pain (IASP) defines pain as an unpleasant sensory and emotional experience associated with actual or potential tissue damage (Bushnell et al, 2013; Aydede, 2019; Meda et al, 2019). Approximately 20–50% of the patients with chronic pain have been reported to have anxiety (Vincent et al, 2015). Electroacupuncture Alleviates Chronic Pain-Induced Anxiety evidence that anxiety may increase the sensation of pain or decrease pain tolerance (Becker et al, 2018; Gong et al, 2018). The mutual influence of pain and anxiety results in chronic pain aggravation and ineffective treatment. Mitigation of pain-related anxiety is thought to be a potential approach in the treatment of chronic pain. Our previous study showed that EA could mitigate anxiety-like behaviors induced by chronic pain in rats (Du et al, 2017). The mechanism by which EA regulates chronic pain-induced anxiety remains unclear
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