Role of extracellular signal-related kinase 1/2 signal transduction pathway at supraspinal level in maintenance of neuropathic pain in mice

Objective To evaluate the role of extracellular signal-related kinase (ERK) 1/2 signal transduction pathway at the supraspinal level in maintenance of neuropathic pain in mice.Methods Sixty-four Kunming mice,aged 2 months,weighing 18-20 g,were randomly divided into 4 groups (n =16 each):sham operation group (group S),chronic constrictive injury (CCI) group; CCI + U0126 (MEK inhibitor) group; CCI + dimethyl sulfoxide (DMSO) group.Neuropathic pain was induced by CCI.The sciatic nerve was exposed and 4 loose ligatures were placed on the sciatic nerve at 1mmintervals with 4-0 silk thread in CCI,CCI + U0126 and CCI +DMSO groups.On 5 days after CCI,5 μg U0126 (in 5 μl of 5％ DMSO) and 5％ DMSO 5 μl were injected into the lateral cerebral ventricle over 10 s in CCI + U0126 and CCI + DMSO groups,respectively,and the time of.needle retaining was 20 s.Paw withdrawal threshold to mechanical stimulation with yon Frey filament (MWT) and paw withdrawal latency to thermal stimulation (TWL) were measured before operation (baseline),before intracerebroventricular injection (T1),and at 30 min and 2,6,12 and 24h after intracerebroventricular injection (T2-6).Resuits Compared with group S,MWT was significantly decreased and TWL was shortened at T1-6 in CCI and CCI +DMSO groups,and at T1 in CCI + U0126 group (P ＜ 0.05),while no significant change in MWT and TWL was found at T2-6 in group CCI + U0126 (P ＞ 0.05).Compared with group CCI,MWT was significantly increased and TWL was prolonged at T2-6 in group CCI + U0126 (P ＜ 0.05),while no significant change in MWT and TWL was found in group CCI + DMSO (P ＞ 0.05).Conclusion ERK1/2 signaling transduction pathway at the supraspinal level is involved in maintenance of neuropathic pain in mice. Key words: Neuralgia;  Extracellular signal-regulated MAP kinases