To evaluate the effect of ketamine on NOX2 expression in the spinal dorsal horn of rats with neuropathic pain.

Thirty-six healthy male Sprague-Dawley rats, aged 6 weeks, weighing 180-220 g, were randomly divided into three groups (n = 12 each) using a random number table: sham operation group (S group), neuropathic pain group (NP group) and ketamine group (K group). Neuropathic pain was induced by chronic constrictive injury in chloral hydrate-anesthetized rats.Sciatic nerve was exposed and 4 loose ligatures were placed on the sciatic nerve at 1 mm intervals with 4-0 silk thread.In K group, ketamine hydrochloride injection 10 mg/kg was injected intraperitoneally everyday starting from 3 days after operation until 21 days after operation.The equal volume of normal saline was given instead in S and NP groups.At 1 day before operation and 3, 7, 14 and 21 days after operation, the mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured.Three animals were sacrificed after measurement of the pain threshold at 7 days after operation, the L_{4, 5} segment of the spinal cord was removed for determination of NOX2 expression (by Western blot) and NOX2 mRNA expression (by using real-time PCR) in the spinal dorsal horn.

Compared with S group, the MWT was significantly decreased, and the TWL was shortened at 3, 7, 14 and 21 days after operation, and the expression of NOX2 protein and NOX2 mRNA was up-regulated at 7 days after operation in NP and K groups.Compared with NP group, the MWT was significantly increased, and the TWL was prolonged at 7, 14 and 21 days after operation, and the expression of NOX2 protein and NOX2 mRNA was down-regulated at 7 days after operation in K group.

The mechanism by which ketamine mitigates neuropathic pain is related to down-regulation of NOX2 expression in the spinal dorsal horn of rats.

Ketamine; Neuralgia; Spinal cord; NADPH oxidase