The type of neuron which express neuropathic pain-related protein BEGAIN in the spinal dorsal horn

Dynamic reorganization of neuronal circuits in the spinal dorsal horn is assumed to cause sensitization in the neuropathic pain. In our previous study, brain-enriched guanylate kinase associated-protein (BEGAIN) was identified as an increased protein in the spinal dorsal horn in the neuropathic pain and the mechanical allodynia was attenuated in the BEGAIN-knockout mice. BEAGIN-expressing neurons have not yet been identified because BEGAIN protein is detected in highly localized dendritic regions, not in the cell body. To identify BEGAIN-expressing neurons, double in situ hybridization with RNA probes for BEGAIN, VGLUT2, and GAD67 was performed. BEGAIN mRNA was widely observed in the spinal cord and these were detected in both inhibitory and excitatory neurons. Since in our previous study, BEGAIN was detected only in the spinal dorsal horn by Western blot and immunohistochemistry, we attempted to visualize BEGAIN protein-expressing neurons using BEGAIN-iCre driver and Ai9 reporter mice.　 TdTomato positive cells were distributed in the laminae I-III in the spinal dorsal horn and these were colocalized with a neuronal marker NeuN. Approximately 15% of neurons in the laminae I-III expressed tdTomato, of which 4.7% expressed an inhibitory neuronal marker Pax2. These results suggest that BEGAIN expressed inhibitory and excitatory spinal neurons have a role in mechanical allodynia after peripheral nerve injury. Furthermore, these results also indicate that BEGAIN protein expression may be regulated by region- and cell-specific mechanisms in the spinal cord.