Effect of dexmedetomidine and small dose of ketamine on hyperalgesia and expression of brain-derived neurotrophic factor mRNA in spinal cord of rats with neuropathic pain / 中华麻醉学杂志

ABSTRACT

Objective To investigate the effect of dexmedetomidine and small dose of ketamine on the hyperalgesia and brain-derived neurotrophic factor (BDNF) mRNA in the spinal cord of rats with neuropathic pain.Methods Forty-five male Sprague-Dawley rats,weighing 240-270 g,were randomly divided into 5 groups (n =9 each)sham operation group (group S),spinal nerve injury (SNI) group,ketamine group (group K),dexmedetomidine group (group D) and dexmedetomidine + ketamine group (group K+ D).The animals were anesthetized with intraperitoneal 10% chloral hydrate 400 mg/kg.SNI was produced by exposing the sciatic nerve and its branches and ligation and transection of tibial nerve and common fibular nerve in groups SNI,K,D and K + D.In S group,the sciatic nerves and its branches were only exposed but not ligated.In groups D,K and K + D,dexmedetomidine 40 μg/kg (2 ml),ketamine 10 mg/kg (2 ml) and mixture of dexmedetomidine 20μg/kg + ketamine 5 mg/kg (2 ml) were injected intraperitoneally,respectively,once a day for 21 consecutive days starting from 24 h after successful SNI surgery.While the equal volume of normal saline 2 ml was injected instead in S and SNI groups.The paw withdrawal threshold to mechanical stimuli (PWT) was measured at 1 day before surgery,and 3,7,14 and 21 days after surgery.Three rats were sacrificed after measurement of pain threshold at 1 day before surgery,and 7 and 21 days after surgery and the lumbar segments (L4-6) of the spinal cord were removed for determination of BDNF mRNA expression in spinal dorsal horn by real time PCR.Results Compared with group S,the PWT was significantly decreased,and the expression of BDNF mRNA in spinal dorsal horn was up-regulated after surgery in groups SNI,K,D and K + D (P ＜ 0.05).The PWT was significantly higher,and the expression of BDNF mRNA in spinal dorsal horn was lower after surgery in groups K,D and K + D than in group SNI,and in group K + D than in groups K and D (P ＜ 0.05).Conclusion The combination of dexmedetomidine and small dose of ketamine produces a synergistic antinociception in rats with neuropathic pain,and direct or indirect inhibition of BDNF mRNA expression in spinal dorsal horn is involved in the underlying mechanism.