gms | German Medical Science

Objective: Propofol (2, 6-diisopropylphenol), has been found to alleviate post-operative pain clinically. Spinal N-medthyl-D-aspartic acid (NMDA) receptors are subtypes of excitatory glutamate receptors contributing to central sensitisation in pain state. Extracellular regulated protein kinases 1/2 (Erk1/2), P38 mitogen-activated protein kinases (P38), c-Jun N-terminal kinases (JNK) are three important members in Mitogen-activated protein kinases (MAPKs) family activated by NMDA receptors, which play important roles in pain hypersensitivity. This study aims to identify if NMDA receptors and its downstream signalling pathway are involved in propofol-induced analgesia.

Method: The analgesic effect of propofol was tested in formalin model in vivo and neuroblastoma cell line SH-SY5Y in vitro. Rats were randomly allocated into 5 groups (n=5): Nil group; F group: rats with subcutaneous (s.c.) injection of 50 μl of 2.5% formalin into right hind paws; P30min+F 0.6mg/kg/min group: injection of formalin at 30 min after 0.6 mg/kg/min propofol infusion via tail vein for 1h; P30min+F 1mg/kg/min group: injection of formalin at 30 min after 1mg/kg/min propofol; P2h+F 0.6mg/kg/min group: injection of formalin at 2h after 0.6 mg/kg/min propofol; P2h+F 1mg/kg/min group: injection of formalin at 2h after 1 mg/kg/min propofol. Pain scores were evaluated for 1h after injection. Protein expression of NMDA receptor subunit NR2B, Erk1/2, P38 and JNK in the dorsal horn was assessed by Western blot. The influx of calcium through NMDA receptors in SH-SY5Y cells with pre-emptive incubation of 3 μM or 10 μM of propofol for 1h was monitored using a fluorometric method.

Results: Either 30 min or 2h after i.v infusion of 0.6 or 1 mg/kg/min of propofol for 1h reduced nociceptive responses from 20-40 min caused by injection of formalin (P<0.01). Both doses of propofol reduced phosphorylated NR2B in dorsal horn (p<0.01). Expression of phosphorylated Erk1/2, rather than P38 and JNK, decreased in the ipsilateral dorsal horn in both higher and lower dose of propofol pre-treated groups (P<0.01). Pre-treatment of 3 μM or 10 μM propofol for 1 hour before the stimulation of NMDA in SH-SY5Y cells reduced the influx of calcium into cells (P<0.01).

Conclusions: Propofol offers analgesic effect on formalin-induced pain. The analgesic mechanisms of propofol could be attributed to the inhibition of GluN2B activation in spinal dorsal horn. Erk1/2 involves in the downstream signaling pathway of GluN2B receptor.