NRG1-ErbB4 signaling in the cerebrospinal fluid-contacting nucleus regulates thermal pain in mice.

The cerebrospinal fluid-contacting nucleus(CSF-contacting nucleus) is a pair of unique nuclei in the brain parenchyma which has long been demonstrated to play an important role in pain signal processing. However, the role of the CSF-contacting nucleus in postoperative pain is still unclear. Here, our works showed that c-Fos expression in the CSF-contacting nucleus was increased in response to incisional pain. The activation of the CSF-contacting nucleus by chemogenetics could induce thermal hyperalgesia in naive mice without effecting the pain in mice suffering from incision pain. The inhibition of the CSF-contacting nucleus alleviated incision pain, but had no effect on the basal pain in naive mice. Furthermore, with immunofluorescence staining and Western blot techniques, the NRG1-ErbB4 signaling in the CSF-contacting nucleus was upregulated during the acute pain phase. And, by activating NRG1-ErbB4 signaling in the CSF-contacting nucleus specifically, the naïve mice displayed thermal hyperalgesia while inhibiting this signaling could reverse the hyperalgesia caused by CSF-contacting nucleus activation, and execute an analgesic effect during the painful phase in mice. Our study suggested that the CSF-contacting nucleus plays a regulatory role in thermal pain in mice via NRG1-ErbB4 signaling.