The effect of free oxygen radicals and the analgesic effects anti-oxidants on neuropathic pain

The objectives of this study were to examine the role of reactiveoxygen species and oxidative stress in peripheral neuropathy and behaviouralpain responses in experimentally induced chronic constriction injury (CCI) ofsciatic nerve of rat. Effects of N-acetyl-l-cysteine (NAC) and phenyl-N-tertbutylnitrone(PBN) administered intraperitoneally, were also investigated onCCI-induced neuropathic pain in rats.Twenty-three adult male Wistar albino rats weighing 200-250 g wereincluded in the study. Rats were randomly divided into 4 groups. Group IVhad the sham procedure. Group I, II and III were the groups that neuropathywas induced by CCI of the right sciatic nerve by sciatic nerve ligation (SNL)under ether inhalation anaesthesia. 24 hours before the ligation of the sciaticnerve, all rats were investigated using nociceptive behavioural tests. For eachrat, the basal values of behavioural tests, mechanical, thermal and coldstimuli, that were measured by analgesiometer, Von Frey monofilaments andhot/cold plate, were recorded. On the 15th day of the sciatic nerve ligation,intraperitoneal administration of the drugs was performed, 10 mL saline toGroup I, 300 mg/kg NAC to Group II and 100 mg/kg PBN to Group III,respectively. Mechanical hyperalgesia and behavioural analysis wereperformed immediately after the administration (0. hour) and the following 1,3, 5 and 7th hours while the tests for cold allodynia and thermal hyperalgesiawere performed 0, 30, 60 and 90. minutes after the administration. Sciaticnerves from CCI-induced and sham operated rats were obtained on the 16thday of the surgery. A segment of sciatic nerve, approximately 1.5 cm inlength, 5 mm proximal and 5 mm distal to the injured site was used forpreparing the homogenate for biochemical estimation. The tissues were thenanalysed for free radical and antioxidant enzyme activities (Coenzyme Q10,Gluthation, Malondialdehyde) by using HPLC.When compared with the sham group (Group IV), behavioural tests,mechanical, thermal and cold stimuli confirmed the development ofneuropathic pain after the CCI in saline group (Group I). The52malondialdehyde (MDA) levels of ligated sciatic nerves in saline group weresignificantly increased compared to non-ligated sciatic nerves (shamoperated). Coenzyme Q10 levels decreased in the ligated sciatic nerves butthe difference was not significant. Intraperitoneal administration of PBNresulted in significant reduction of mechanical hyperalgesia and cold allodyniaand increase in sciatic nerve MDA levels when compared with the CCIinducedneuropathic rats that were given saline. When compared with NACgroup (group II), the reduction of mechanical and cold allodynia and thedecrease in sciatic nerve MDA levels was more significant in PBN group(group III).In conclusion, the present study suggests that oxidative stress isprobably responsible for the nerve dysfunction. This study identifies MDA asimportant determinants of neuropathological and behavioural consequencesof CCI-induced neuropathy, and PBN may be a potential candidate foralleviation of neuropathic pain as it relieves SNL-induced mechanicalhyperalgesia and cold allodynia.