ROLE OF SPINAL DORSAL HORN BEGAIN IN NEUROPATHIC AND INFLAMMATORY PAIN: INSIGHTS FROM CONDITIONAL KNOCKOUT MICE

Neuropathic and inflammatory pain are maintained over long periods by plastic changes in the central nervous system. Previously, we focused on molecules within the postsynaptic density (PSD) fraction of the spinal dorsal horn and identified brain-enriched guanylate kinase-associated protein (BEGAIN) as a molecule upregulated in a neuropathic pain model. We reported that mechanical allodynia in neuropathic pain models is attenuated in global BEGAIN knockout (KO) mice (eNeuro, 2016). BEGAIN expression is observed in both the spinal dorsal horn and the supraspinal regions (Mol Brain, 2023), and central sensitization in chronic pain occurs in both areas. In this study, we focused on BEGAIN in the spinal dorsal horn, and its expression patterns and cell types were analyzed using a BEGAIN-iCre driver and Ai9 reporter mice. Furthermore, we generated spinal dorsal horn-specific BEGAIN conditional knockout (cKO) mice to investigate the role of BEGAIN in pathological pain. In BEGAIN-iCre::Ai9 mice, where BEGAIN-expressing cells are labeled with tdTomato, we analyzed the distribution and colocalization of BEGAIN with NeuN, Iba1, and GFAP. BEGAIN-positive cells were primarily distributed in laminae I–III. TdTomato-positive cells colocalized with the neuronal marker NeuN; however, no colocalization with the glial markers Iba1 or GFAP was observed. Behavioral analysis using von Frey filaments showed that while mechanical allodynia developed in wild-type mice after spared nerve injury (SNI) or CFA injection, this allodynia was significantly attenuated in both global and conditional BEGAIN-KO mice. These results indicate that BEGAIN in spinal dorsal horn neurons plays a critical role in pathological pain transmission.