Effects On The Peripheral Anti-hyperalgesia And Study On Neurotoxicologic Screening Of Amitriptyline For Sciatic Nerve Blockade On Neuropathic Pain Of Rats

Background & Objective: Tricyclic antidepressants(TCAD), waswidely administered systemically to relieve neuropathic pain in human.Studies have confirmed that amitriptyline has local anesthetic properties evenmore potent than bupivacaine for sciatic nerve block in rats.The aim of thisstudy was to investigate if the peripheral administration of amitriptylineproduces anti-hyperalgesic effect and to screen the neurotoxicological effectsfor sciatic nerve blockade.in a rat model of neuropathic pain.Methods:(1) Establishment of chronic constriction injury (CCI)model of sciatic nerve16 healthy male adult SD rats were randomly divided into experimentgroup(CCI) and control group(Sham). The sciatic nerve of the right hind legwas constricted in CCI group and the sciatic nerve of the right hind leg wasexposed without any injury in control group. The mechanical withdrawalthreshold(MWT) and thermal withdrawal latency(TWL) were measuredbefore operation and on 1d, 3d, 5d, 7d, 14d, 21d after operation.(2) Peripheral anti-hyperalgesic effect of amitriptyline for sciatic nerveblockade on neuropathic pain of rats On the chronic constriction injury (CCI) rats,48 rats were randomly divided into 6 groups(n=8).NS group, A_2.5group, A₅ group, A₁₀ group, A_15.9 group and A_ip group. In the NS group,A_2.5 group, A₅ group, A₁₀ group, A_15.9 group, Sciatic nerve blockade waslocally performed with 0.5ml normal saline, 2.5mM,5mM,10mM or15.9mM amitriptyline respectively through implanted cannulas on the 7thday after operation. In the A_ip group,amitriptyline (2.5mg) wasadministered by intraperitoneal(i.p.) injection. The mchanical withdrawalthreshold (MWT),thermal withdrawal latency (TWL)and motor functionwere measured before and on 1h, 2h, 4h, 8h, 12h, 24h, 48h after sciatic nerveblockade.(3) Peripheral anti-hyperalgesic effect and Neurotoxicologic Screening,of Amitriptyline for Sciatic nerve blockade Chronically on neuropathicpain for rats 24 healthy male adult SD rats were randomized into 3 groups(n=8).From the 5th days after operation of sciatic nerve chronic constrictioninjury (CCI), the operated sciatic nerve blockade was performed once a dayfor successive 3 days with 0.5ml normal saline, 0.5% amitriptyline or 0.5%bupivacaine in normal saline (NS) group, amitriptyline (A) group andbupivacaine (B) group respectively. Mechanical withdrawal threshold(MWT), thermal withdrawal latency (TWL) and motor function weremeasured before and on 1d, 3d, 5d, 7d after the third sciatic nerve blockade.After behavioral observation all rats were anesthetized with2.5%pentobarbital(70mg/kg) and the operated sciatic nerve was sampled forneuropathological examination under light microscope.Results:(1) The MWT and TWL of CCI group were significantly decreasedcompared with those in group control(P＜0.05). (2) The MWT and TWL of groups with local injection of amitriptylineincreased than that of NS group, A_ip group and those of beforeinjection(P＜0.05).Sciatic nerve blockade with amitriptyline significantlysuppressed mechanical hyperalgesia and thermal hyperalgesia inneuropathic rats. The peripheral anti-hyperalgesic effects lasted 2h(A_2.5group), 4h(A₅group), 24h(A₁₀group), 24h(A_15.9group) respectively.But there were no significant difference (P＞0.05) observed between A₁₀group and A_15.9 group. There were no significant difference (P＞0.05)observed between NS group and A_ip group.(3) There was no anti-nociceptive effect observed in NS group. The MWTand TWL in group A significantly increased than that of group NS,group B and before injection (P＜0.05).This effect of amitriptyline lasted3 days. Bupivacaine hadn't such effect. Similar (P＞0.05) movementdisorder occurred in both group A and group B and was reversible.Therewere no significant difference (P＞0.05) observed among three groups onlight microscopic neuropathological examination..Conclusion:(1) The animal model of CCI is easy to duplicate and can exhibit many ofclinical signs of neuropathic pain, including hyperalgesia, spontaneouspain, and allodynia. And it has been proved useful in improving theunderstanding of both the mechanisms contributing to the developmentof neuropathic pain as well as of potential analgesic treatments.(2)The peripheral anti-hyperalgesic effects have beeen found in sciatic nerveblockade of amitriptyline on neuropathic pain of rats. And this effect ofamitriptyline has concentration dependent and "ceiling" effect.(3)Repeated sciatic nerve blockade with 0.5% amitriptyline had peripheralanti- hyperalgesic effects on neuropathic pain of rats.And this effect lasted 3 days. The disorder of movement in behavior was reversible. Nomorphological evidence of neurotoxicity in the sciatic nerve of rats wasobserved in 0.5%amitriptyline.