Taselisib moderates neuropathic pain through PI3K/AKT signaling pathway in a rat model of chronic constriction injury.

BACKGROUND: Neuropathic pain is a chronic condition commonly caused by inflammation-induced disturbances or lesions of somatosensory functions in the nervous system. The aim of this study was to investigate the effects and mechanisms of Taselisib on chronic constriction injury (CCI)-induced neuropathic pain in rats. METHODS: The rats were divided into four groups: sham group, sham + Taselisib (10 mg/kg orally once a day) group, CCI group, and CCI + Taselisib (10 mg/kg orally once a day) group. Pain behavioral tests, recorded by measuring paw withdrawal threshold (PWT) and thermal withdrawal latency (TWL), were conducted on days 0, 3, 7, 14, and 21 after surgery. After testing, the animals were euthanized and spinal dorsal horns were collected. Pro-inflammatory cytokines were quantified using ELISA and qRT-PCR. PI3K/pAKT signaling was assessed using Western blot and immunofluorescence. RESULTS: PWT and TWL were significantly reduced after CCI surgery, but were successfully increased by Taselisib treatment. Taselisib treatment notably suppressed the upregulation of pro-inflammatory cytokines, including IL-6, IL-1ß, and TNF-⍺. Taselisib treatment significantly reduced the elevated phosphorylation of AKT and PI3K induced by CCI. CONCLUSION: Taselisib can alleviate neuropathic pain by inhibiting the pro-inflammatory response, potentially through the PI3K/AKT signaling pathway.

Dexmedetomidine alleviates traumatic spinal cord injury in rats via inhibiting apoptosis induced by endoplasmic reticulum stress.

OBJECTIVE: To investigate the protective effect of dexmedetomidine (Dex) on traumatic spinal cord injury (TSCI) and to evaluate the involvement of inhibition of endoplasmic reticulum (ER) stress response in the potential mechanism. METHOD: Sprague-Dawley rats were randomly divided into five groups. The hind limb locomotor function of rats was evaluated at 1, 3 and 7 days after the operation. At 7 days after the operation, spinal cord specimens were obtained for hematoxylin and eosin (H&E), Nissl and TUNEL staining, as well as immunofluorescence and Western blot analyses to detect the level of apoptosis and the levels of proteins related to ER stress. RESULTS: 7 days after the operation, Dex treatment promoted the recovery and also inhibited apoptosis of neurons in the spinal cord. Additionally, Dexinhibited the expression of proteins related to ER stress response after spinal cord injury. CONCLUSIONS: Dex improves the neurological function of rats with TSCI and reduces apoptosis of spinal cord neurons. The potential mechanism is related to the inhibition of the ER stress response.