Role of the RVM in Descending Pain Regulation Originating from the Cerebrospinal Fluid-Contacting Nucleus

Abstract

Evidence has suggested that cerebrospinal fluid-contacting nucleus (CSF-contacting nucleus) is correlated with the development and recurrence of pain. A recent research showed that the CSF-contacting nucleus acts as a component of the descending 5-hydroxytryptamine (5-HT) system and plays a role in descending pain inhibition. However, limited studies are conducted to investigate the relationship between the CSF-contacting nucleus and pain. In present study, we explored the effect of CSF-contacting nucleus on nociceptive behaviors in both normal and neuropathic rats via targeted ablation of the CSF-contacting nucleus in the brainstem, using cholera toxin subunit B-saporin (CB-SAP), a cytotoxin coupled to cholera toxin subunit B. The CB-SAP-treated rats showed aggravated thermal hyperalgesia and mechanical allodynia. Also, results from immunohistochemical experiments showed that rostral ventromedial medulla (RVM) received fiber projection from the CSF-contacting nucleus, which disappeared after ablation of the CSF-contacting nucleus, and the CB-SAP treated rats showed downregulation of c-Fos expression in the RVM as compared with the rats receiving i.c.v. injection of phosphate buffer saline (PBS). A significant downregulation of 5-HT-labeled neurons and tryptophan hydroxylase 2 (TPH2) as the marker of 5-HT cells in the RVM, and 5-HT expression in spinal dorsal horn in both normal and chronic constriction injury (CCI) rats after i.c.v. injection of CB-SAP was observed. These results suggested that RVM may be involved in descending pain modulation originating from the CSF-contacting nucleus.