The comparison of pregabalin and Phenyl-N-Nitrone effects at the neuropathic pain model of rats

The objectives of this study were to examine the role of reactive oxygen species and oxidative stres in peripheral neuropathy and the effects of PBN to hinder the neuropathic pain. The role of PBN and pregabalin were also investigated on neuropathic pain treatment in rats.Twenty-four adult female Wistar albino rats weighing 230-250 g were included in the study. Rats were randomly divided into 4 groups. Group IV had the sham procedure. Group I, II and III were the groups that neuropathy was induced by CCI of the right sciatic nevre ligation under ether inhalation anaesthesia. 24 hours before the ligation of the sciatic nevre, all rats were investigated using nociceptive behavioural tests. For each rat, the basal values of behavioural tests, mechanical, thermal and cold stimuli, that were measured by analgesiometer, mechanical allodini dynamic plantar eisteziometer and hot/cold plate, were recorded. On the 15 th day of sciatic nerve ligation, intraperitoneal administration of the drugs was performed. 2 ml saline group I, 30 mg/kg pregabalin to group II and 100 mg/kg PBN to group III respectively. Mechanical hyperalgesia and dynamic plantar eisteziometer mechanical allodynia were performed the following 1, 3, 5 and 7 th hours while the tests for cold allodynia and thermal hyperaljesia were performed. 30, 60 and 90. minutes after the administration. Sciatic nerves from CCI induced and sham operated rats were obtained on the 16 th day of the surgery. A segment of sciatic nerve, approximately 1,5 cm in length, 5 mm proximal and 5 mm distal to the injured site was used for preparing the homogenate for biochemical estimation. The tissues were then analysed for free radical and antioxidant enzyme activities (Coenzyme Q10, gluthation, malondialdehyde) by using HPLC and by using Griess reaction spectrophotometric NO measurements were estimated.When compared with the sham group, behavioural tests, mechanical, thermal and cold stimuli confirmed the development of neuropathic pain after the sciatic nerve ligation in saline group. That shows the succes of neuropathic pain model (sciatic nerve ligation). Data suggest that either pregabalin was effective of thermal hyperalgesia, mechanical hyperalgesia, cold and mechanical allodynia where PBN was only effective thermal hyperalgesia.Glutation levels of ligated sciatic nerves in saline group were decreased compared to non-ligated sciatic nerves(sham group). Coenzyme Q10 level significantly decreased in the ligated sciatic nerves compored to sham group were significantyly increased in PBN group. While MDA level were increased in saline group, were decreased in PBN group. These results show that oxidative stres increases in neuropathic pain and PBN has antioxidant feature. The other biochemical parameter which was measured NO level. It is determined that according to sham, NO levels were increased in saline group and decreased when PBN and pregabalin were administered. According to this result it is thought that pregabalin &PBN are effective in neuropathic pain by suppressing the NO mechanism.In conclusion, PBN can be effective in treatment of neuropathic pain. Though it's effects are not as inclusive as pregabaline, in other words, ROS cleanes are not an alternative to Ca channel blockers but are agents that can be used together with Ca channel blockers to make an additive or sinergist effect.