Activation of CB1R within the rostral ventromedial medulla alleviates central sensitization induced by paradoxical sleep deprivation in a plantar incision rat model

Background Cannabinoid receptor 1 (CB1R) in the rostral ventromedial medulla (RVM) of rats has been shown to exert antinociceptive effects by altering synaptic plasticity in inflammatory and neuropathic pain models. However, the role of CB1R in the central sensitization due to paradoxical sleep deprivation (PSD) is unclear. Methods Male Sprague-Dawley rats were subjected to PSD for 24 hours one day before surgery, and then a plantar incision model was established. Mechanical threshold was used to evaluate hyperalgesia. The mRNA and protein levels of CB1R in RVM were detected by qRT-PCR and western blotting. WIN-55,212-2(a CB1R agonist) and SR141716(a CB1R antagonist) were injected into RVM, the expression of CB1R was detected by immunofluorescence, the mRNA and protein levels of CB1R in the RVM were again detected, and the pain degree was assessed by mechanical threshold. To investigate the role of CB1R in the process of central sensitization. Results We found that a 24-hour period of PSD before surgery significantly increased pain sensitivity and duration of postoperative pain in rats after incisional surgery. Compared with rats that received only plantar incision, preoperative PSD for 24 h increased CB1R expression in the RVM of rats after incision. Furthermore, the injection of CB1R agonist into the PSD and incisional model rat RVM 1 day after surgery significantly reduced pain, while the CB1R inhibitor increased nociceptive hypersensitivity. Conclusions These data reveal that activation of CB1R in the RVM alleviates preoperative PSD-induced incision pain sensitization. Activation of CB1R might have a positive effect on the prevention of pain sensitization after PSD by reducing central sensitization.