The Role of Skin Mast Cells in Acupuncture Induced Analgesia in Animals: A Preclinical Systematic Review and Meta-analysis

While mast cells (MCs) are previously well-known as a pathological indicator of pain, their role in alleviating pain is recently emerged in acupuncture research. Thus, this study systematically reviews the role of MC in acupuncture analgesia. Animal studies on MC changes associated with the acupuncture analgesia were searched in PubMed and EMBASE. The MC number, degranulation ratio and pain threshold changes were collected as outcome measures for meta-analyses. Twenty studies were included with 13 suitable for meta-analysis, most with a moderate risk of bias. A significant MC degranulation after acupuncture was indicated in the normal and was significantly higher in the pain model. In the subgroup analysis by acupuncture type, manual (MA) and electrical (EA, each P < .00001) but not sham acupuncture had significant MC degranulation. Meta-regression revealed the linear proportionality between MC degranulation and acupuncture-induced analgesia (P < .001), which was found essential in MA (P < .00001), but not in EA (P = .45). MC mediators, such as adenosine and histamine, are involved in its mechanism. Taken together, skin MC is an essential factor for acupuncture-induced analgesia, which reveals a new aspect of MC as a pain alleviator. However, its molecular mechanism requires further study. PERSPECTIVE: This systematic review synthesizes data from studies that examined the contribution of skin MC in acupuncture analgesia. Current reports suggest a new role for skin MC and its mediators in pain alleviation and explain a peripheral mechanism of acupuncture analgesia, with suggesting the need of further studies to confirm these findings.