Substance P expression in the distal cerebrospinal fluid-contacting neurons and spinal trigeminal nucleus in formalin-induced the orofacial inflammatory pain in rats

The distal cerebrospinal fluid-contacting neuron (dCSF-CN) is a peculiar type of neuron whose body is in the parenchyma of the brain and processes extend into cerebrospinal fluid (CSF) in the cavity of the ventricle in the central nervous system. Because most of the dCSF-CNs are found in the dorsal raphe nucleus (DR) of the brainstem, we presume these neurons relate to pain modulation. Many experiments have demonstrated that substance P (SP) plays an important role in the development of pain and hyperalgesia. To explore whether the dCSF-CNs modulated the orofacial inflammatory pain in rats, we examined behavioral changes with the orofacial formalin test and SP-expression in the dCSF-CNs and spinal trigeminal nucleus (STN) with dual immunohistochemical labeling for light microscopy or immunoelectron microscopy. It is revealed that 2 h after 2.5% formalin injection SP-expression in the dCSF-CNs and STN is upregulated significantly, which may be considered an important role for nociceptive processing.