Electroacupuncture Alleviates Chronic Pain-Induced Anxiety Disorders by Regulating the rACC-Thalamus Circuitry

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.

Rostral Anterior Cingulate Cortex–Ventrolateral Periaqueductal Gray Circuit Underlies Electroacupuncture to Alleviate Hyperalgesia but Not Anxiety-Like Behaviors in Mice With Spared Nerve Injury

“…While anxiety-like behaviors were relieved by EA, the anxiolytic effect could not be reversed by activating the rACC Glu -vlPAG pathway. In contrast, our previous study has revealed that inhibition of the rACC Glu -thalamus circuit alleviated anxiety-like behaviors in CFA rat models but did not affect the mechanical pain threshold (Shen et al, 2020). Furthermore, activation of the rACC Glu -thalamus pathway specifically reversed the anxiolytic effect of EA in CFA rat models but had no effect on pain sensation.…”

Electroacupuncture Ameliorates Chronic Inflammatory Pain-Related Anxiety by Activating PV Interneurons in the Anterior Cingulate Cortex

“…Another animal study showed that injection of an excitatory glutamate antagonist into the ACC prevented formalin-induced positional aversion without relieving formalin-induced acute inflammatory pain ( Johansen and Fields, 2004 ). In addition, our previous study found that inhibiting glutamatergic neurons in the ACC-thalamic neural circuity can interfere with pain-induced anxiety-related emotions ( Shen et al, 2020 ). There is no doubt that all of this evidence suggests that hyperexcitability of the ACC is involved in pain and pain-related negative emotions.…”

TRPV1 Responses in the Cerebellum Lobules VI, VII, VIII Using Electroacupuncture Treatment for Chronic Pain and Depression Comorbidity in a Murine Model

“…The modern clinical application of acupuncture involves the use of an electrical stimulator to produce increased signal and response mechanisms within the central nervous system [ 20 ]. The application of this stimulating method, known as electroacupuncture (EA), has displayed a proficient aptitude in the treatment of a large variety of chronic pain conditions [ 21 , 22 ], as well as several psychological conditions [ 16 ]. Furthermore, the neurological signaling cascades involved in the mediation of CPDC can be activated through ST36 (zusanli), a TRPV1 responding mechanosensitive acupoint generally used in clinical regimes [ 23 ].…”