Electroacupuncture alters cannabinoid receptor 1 and transient receptor potential V1 expression on individual brain regions in a mouse fibromyalgia model

Fibromyalgia, one of the most challenging pains to treat, lacks impartial considerations for diagnosis and useful assessment. The core symptoms are persistent extensive pain accompanied by fatigue, psychological disorders, sleep disturbance, and obesity. The current study aims to explore the role of cannabinoid receptor 1 (CB1) signaling pathways in a mouse model of fibromyalgia. This model was subjected to intermittent cold stress (ICS) to induce fibromyalgia, as measured by the nociceptive behavior determined by von Frey and Hargraves’ tests. Our results showed lower mechanical threshold (2.32 ± 0.12 g) and thermal latency (4.14 ± 0.26 s) in ICS-induced fibromyalgia mice. The hyperalgesia could be alleviated by electroacupuncture (EA) or by transient receptor potential V1 (TRPV1) knockout. We found differential expression of CB1 and TRPV1 signaling molecules in specific brain regions: upregulated TRPV1 and related kinases in the dorsal root ganglion, spinal cord, hypothalamus and periaqueductal gray region, and decreased CB1 receptor composition. EA reversed these effects associated with fibromyalgia, aligning with observations in Trpv1 ^−/− mice. Peripheral acupoint or intracerebral ventricle injection of a CB1 agonist or antagonist significantly regulated hyperalgesia through the CB1 signaling pathway. Our discoveries shed light on the involvement of CB1 on the TRPV1 pathway in the effects of EA in fibromyalgia, suggesting its potential as a treatment target.