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

Abstract

Depression is a prominent complex psychiatric disorder, usually complicated through expression of comorbid conditions, with chronic pain being among the most prevalent. This comorbidity is consistently associated with a poor prognosis and has been shown to negatively impact patient outcomes. With a global rise in this condition presenting itself, the importance of discovering long-term, effective, and affordable treatments is crucial. Electroacupuncture has demonstrated renowned success in its use for the treatment of pain and is a widely recognized therapy in clinical practice for the treatment of various psychosomatic disorders, most notably depression. Our study aimed to investigate the effects and mechanisms of Acid-Saline (AS) inducing states of chronic pain and depression comorbidity in the cerebellum, using the ST36 acupoint as the therapeutic intervention. Furthermore, the role of TRPV1 was relatedly explored through the use of TRPV1−/− mice (KO). The results indicated significant differences in the four behavioral tests used to characterize pain and depression states in mice. The AS and AS + SHAM group showed significant differences when compared to the Control and AS + EA groups in the von Frey and Hargreaves’s tests, as well as the Open-Field and Forced Swimming tests. This evidence was further substantiated in the protein levels observed in immunoblotting, with significant differences between the AS and AS + SHAM groups when compared to the AS + EA and AS + KO groups being identified. In addition, immunofluorescence visibly served to corroborate the quantitative outcomes. Conclusively these findings suggest that AS-induced chronic pain and depression comorbidity elicits changes in the cerebellum lobules VI, VII, VIII, which are ameliorated through the use of EA at ST36 via its action on TRPV1 and related molecular pathways. The action of TRPV1 is not singular in CPDC, which would suggest other potential targets such as acid-sensing ion channel subtype 3 (ASIC3) or voltage-gated sodium channels (Navs) that could be explored in future studies.

Brain Activities Responding to Acupuncture at ST36 (zusanli) in Healthy Subjects: A Systematic Review and Meta-Analysis of Task-Based fMRI Studies

“…Recent evidence from animal experiments has shown the neuroanatomical basis of ST36 in driving the vagal-adrenal axis, thus modulating anti-inflammatory responses in mice (12). Research in healthy individuals demonstrated the effects of ST36 in the somatosensory and motor areas, cerebellum, and limbic system (13,14). A meta-analysis on block-design fMRI, including both patients and healthy individuals, demonstrated that acupuncture at ST36 with deqi sensation exclusively activates the right hemisphere of the brain, such as the right orbital part of the inferior frontal gyrus (IFG), right median cingulate, and paracingulate gyri, right supramarginal gyrus, and pons (15).…”

Electroacupuncture attenuates LPS-induced depression-like behavior through kynurenine pathway

“…Therefore, we established an inflammation-induced depression model and measured depression-like behaviors, inflammatory cytokines, glutamate level, and kynurenine metabolisms to find to measure the function of EA on depression. We observed EA could treat pathological inflammation ( Zhang et al, 2015 ), and as observed in the tail suspension test (TST) and forced swimming test (FST) behavioral responses, EA significantly attenuated depressive behavior ( Lottering and Lin, 2021 ). Moreover, in the nervous system, EA could ameliorate glutamate and regulate kynurenine metabolisms.…”

Relationship between acupuncture and transient receptor potential vanilloid: Current and future directions

“…Meanwhile, stimulation at acupoints could lead to a multi-targeted effect on the central nervous system. For example, after stimulation at ST36, the changes of TRPV channels in the spinal cord ( Yang et al, 2017 ); cerebellum lobules V, VIa, VI, VII, and VIII ( Inprasit and Lin, 2020 ; Lottering and Lin, 2021 ); hippocampus; periaqueductal gray; and medial prefrontal cortex ( Lin et al, 2020 ) could be observed.…”

“…Phosphorylation of downstream molecules was widely found after acupuncture-regulated TRPV channels ( Inprasit et al, 2018 ). Inprasit and Lin (2020) and Lottering and Lin (2021) performed a series of studies to clarify the role of acupuncture and TRPV in the cerebellum lobules. Both complete Freund’s adjuvant (CFA) and acid saline (AS) could lead to chronic pain, but the expression of TRPV1 in the cerebellum lobules is completely opposite.…”