Effects Of Intraperitoneal Ketamine On Chronic Neuropathic Pain In Rats

Objective: According to the The international association for the study of pain , IASP, neuropathic pain is the pain caused by the injury or disorder of the nerve system. Neuropathic pain is very common and had a direct impact on patient quality of life.Katemine is wildly used in clinical anathsia . GAP-43 is associated with central sensitization . Central sensitization is an important factor of the chronic neuropathic pain.The persent study coping the Bennett and Xie's CCI rat model is to evaluate the effects and the mechanism of intraperitoneal ketamine on chronic neuropathic pain in rats. And the study could help finding out more specific target of treatment for chronic neuropathic pain.Methods: Seventy-five male SD rats weighing 200±20g were randomly assigned to one of three groups, twenty-five in each group:groupⅠ(C)sham operation; groupⅡ(CCI) chronic constriction injury ;and groupⅢ(K) intraperitoneal ketamine. The animals were anesthetized with intraperitoneal 10% chloral hydrate 300mg/kg.The right sciatic nerve was exposed and four ligatures were placed in group CCI and K. Katemine 10mg/kg was given intraperitoneal at 3～21 day after surgery in group K .50% mechanical withdrawal threshold (MWT) to von Frey filament stimulation,nerve conduction velocity(NCV) were measured before (T0) and at 3,7,14 and 21 days after surgery (T1-T4).The animals were then killed ,the sciatic nerve was exposed to observe the neuro changes in general and at electron microscopy of the ultrastructure .The lumbar segment of the spinal cord dorsal horn was removed for determination of the expression of GAP-43 protein and GAP-43mRNA.Results:1 Mechanical withdrawal threshold (MWT) Compared with T0, the MWT was significantly reduced at 3～21 day after surgery (T1-T4) (P<0.05) ; Compared with group C, the MWT was significantly reduced at 3～21 day after surgery (T1-T4) (P<0.05); the MWT was significantly higher at T2-T4 in group K than in group CCI (P<0.05).2 nerve conduction velocity (NCV) Compared with T0, the NCV was significantly reduced at 7-21 day after surgery (T2-T4) (P<0.05); Compared with group C, the NCV was significantly reduced at 7～21 day after surgery (T2-T4) (P<0.05); the NCV was significantly higher at T2-T4 in group K than in group CCI (P<0.05).3 Electron microscopy Observation The neural structure was rule and integrity; in group C; in the group of CCI , neural axons were fractured, myelin was thinning ,microfilaments and microtubules were reduced from 7 to 21 day . In the group of K ,myelin was thickening and lamellar changing rule from 14 to 21 day .4 The expression of GAP-43 in spinal cord dorsal horn Compared with group C, the expression of GAP-43 protein was significantly increased at 3～21 day after surgery (T1-T4) (P<0.05) ; the expression of GAP-43 protein was decreased significantly at T1-T4 in group K than in group CCI (P<0.05). The expression of GAP-43 mRNA in spinal cord dorsal horn was the same to the GAP-43 protein.Conclusion:1 Intraperitoneal Katemine had an effort on chronic neuropathic pain in rats.2 The possible mechanism of intraperitoneal Katemine inhibiting neuropathic pain is reducing the expression of GAP-43 in the spinal cord dorsal horn.