Electroacupuncture alleviates mechanical allodynia and anxiety‐like behaviors induced by chronic neuropathic pain via regulating rostral anterior cingulate cortex‐dorsal raphe nucleus neural circuit

Abstract

AimsEpidemiological studies in patients with neuropathic pain have demonstrated a strong association between neuropathic pain and psychiatric conditions such as anxiety. Preclinical and clinical work has demonstrated that electroacupuncture (EA) effectively alleviates anxiety‐like behaviors induced by chronic neuropathic pain. In this study, a potential neural circuitry underlying the therapeutic action of EA was investigated.MethodsThe effects of EA stimulation on mechanical allodynia and anxiety‐like behaviors in animal models of spared nerve injury (SNI) were examined. EA plus chemogenetic manipulation of glutamatergic (Glu) neurons projecting from the rostral anterior cingulate cortex (rACCGlu) to the dorsal raphe nucleus (DRN) was used to explore the changes of mechanical allodynia and anxiety‐like behaviors in SNI mice.ResultsElectroacupuncture significantly alleviated both mechanical allodynia and anxiety‐like behaviors with increased activities of glutamatergic neurons in the rACC and serotoninergic neurons in the DRN. Chemogenetic activation of the rACCGlu‐DRN projections attenuated both mechanical allodynia and anxiety‐like behaviors in mice at day 14 after SNI. Chemogenetic inhibition of the rACCGlu‐DRN pathway did not induce mechanical allodynia and anxiety‐like behaviors under physiological conditions, but inhibiting this pathway produced anxiety‐like behaviors in mice at day 7 after SNI; this effect was reversed by EA. EA plus activation of the rACCGlu‐DRN circuit did not produce a synergistic effect on mechanical allodynia and anxiety‐like behaviors. The analgesic and anxiolytic effects of EA could be blocked by inhibiting the rACCGlu‐DRN pathway.ConclusionsThe role of rACCGlu‐DRN circuit may be different during the progression of chronic neuropathic pain and these changes may be related to the serotoninergic neurons in the DRN. These findings describe a novel rACCGlu‐DRN pathway through which EA exerts analgesic and anxiolytic effects in SNI mice exhibiting anxiety‐like behaviors.

Research Trends of Acupuncture Therapy for Chronic Pain-Related Depression or Anxiety from 2003 to 2023: A Bibliometric Analysis

“…Some animal studies have indicated that electroacupuncture exhibits the potential to alleviate chronic neuropathic pain-related depression or anxiety, primarily through its modulation of various molecular targets and neural circuits. 22 , 53–56 What’s more, our results showed that the RCTs and evidence-based evaluation were the current research type. By conducting rigorous RCTs and Meta-analysis, we can accurately ascertain the efficacy of acupuncture.…”

Neural circuit mechanisms of acupuncture effect: where are we now?

“…Shen et al ( 38 ) found that electroacupuncture can treat anxiety-like behavior in Complete Freund’s Adjuvant (CFA) model rats by activating the rACC Glu-thalamus circuit without affecting pain. Xu et al ( 40 ) found that electroacupuncture can exert analgesic and anxiolytic effects on spared nerve injury (SNI) model mice by activating the rACC Glu-dorsal raphe nucleus (DRN) circuit. Hsiao et al ( 41 ) found that electroacupuncture to the Zusanli (ST36) could treat chronic inflammatory pain by inhibiting CaMKIIα signaling in the somatosensory cortex (SSC)-anterior cingulate cortex (ACC) circuit.…”

The impact of electroacupuncture on anxiety-like behavior and gut microbiome in a mouse model of chronic restraint stress

“…Extensive research has already highlighted the positive effects of EA in alleviating symptoms associated with various neuropsychiatric conditions ( Li X. et al, 2019 ; Tamtaji et al, 2019 ; Wang et al, 2019 ). Furthermore, animal studies have demonstrated the capacity of EA to ameliorate behaviors related to anxiety, and clinical studies have confirmed its anxiolytic effects ( Amorim et al, 2022 ; Wu et al, 2022 ; Xu et al, 2023 ). Collectively, these findings suggest that EA treatment could serve as a promising complementary therapy for anxiety disorders.…”