Effect Of Low-dose Ketamine And Morphine On Expression Of P2X₄ Receptor Of The Rats With Chronic Neuropathic Pain

Objective: To observe the effects of continuous intraperitoneal injection low dose ketamine and morphine on thermal hyperalgsia and expression of P2X₄ receptor on spinal cord horn cerebral cortex and hippocampous of CCI rats ,to explore the potential mechanism of neuropathic pain induced by P2X₄ receptor.Method: 32 Sprague-Dawley rats weighing 160-200g ,were randomly divided into 4 groups(n=8): group S(sham group), group C:CCI + normal saline; group K:CCI+ketamine(10mg·kg^-1) ;group KM : CCI + ketamine (5mg·kg^-1) + morphine(1mg·kg^-1) .After 3 days, thermal hyperslgesia was determined by examining thermal nociceptive threshold, then the CCI rats were intraperitoneal injected normal saline ketamine ketamine and morphine respectively (diluted in physiological saline solution to 2ml).TWL were determined with thermal radiation apparatus 1 days before the operation and 1,3,7,14days after the operaton respectively; the expression of P2X₄ receptor in the spinal cord cerebral cortex and hippocampous were assessed 7 and 14 days after operation using immunohistochemistry.Results:TWL of surgical sides between groups have not a significant P value (P>0.05 ) . Compared to pre-operation ,the TWL of the surgical side in group S decreased slightly(P>0.05). TWL were significant lower in group C , group K and group KM than in pre-operation and S group aftert 3 days of the operation(P<0.05), espeacially on 14 days,but there was no significant difference among group C, group K and group KM. TWL in group K and group KM elevated significently compared to group C on 7 days after the operation(P<0.05), espeacially on 14 days.Compared to group K, TWL of group KM also elevated significently (P<0.05).Immunohistochemistry : Compared to group S,expression of P2X₄ receptor of group C,K and KM in spinal cord horn cerebral cortex and hippocampous were increased significently on 7,14 days after operation,espeacially on 14 days(P<0.01) .expression of P2X₄ receptor of group K and group KM decreased obviously compared to group C (P<0.05),especially in group KM.Expression of P2X₄ receptor in group KM were fewer than that in group K(P<0.05).Most of the P2X₄ receptor positive cells displayed the form of activated microglial.conclusion:1 ketamine can enhance the antinociceptive effect of morphine with subthreshold dose.2 Expression of P2X₄ receptor increase on spinal cord horn cerebral cortex and hippocampous in neuropathic pain rats ,indicate that P2X₄ receptor may play an important role in the transduction of nociceptive message.3 Intraperitoneal injection ketamine or ketamine and morphine can inhibit the expression of P2X₄ receptor on the spinal corn hord cerebral cortex and hippocampous,inferred that the analgesic effect of ketamine or ketamine and morphine is achieved at least by inhibiting the expression of P2X₄ receptor directly or indirectly.