Effects Of Mitochondria-targeted Antioxidant On Pain Behaviors In Neuropathic Pain Rats And Its Mechanism

Objective Pain arising as a direct consequence of a lesion or disease affecting the somatosensory system is named neuropathic pain(NP).Analgesics often fail in alleviating NP.It's reported that reactive oxygen species(ROS)plays an important role in neuropathic pain development,ROS scavenger can alleviate neuropathic pain.Mitochondrial membrane permeability transition pore(m PTP)is a complex that exists between inside and outside mitochondria membrane,and plays an important role in cell survival and apoptosis.Lots of ROS will cause m PTP opening and a series of physiological changes.Transient receptor potential vanilloid receptor 1(TRPV1)is one of the members of the family of transient receptor potential(TRP),and mainly expresses in primary afferent sensory neurons,and closely related to the pain conduction and modulation.Activation of TRPV1 can mediate substance P release.Excessive ROS produced will sensitize TRPV1.Mitochondria-targeted antioxidants can specifically gather in mitochondria and remove excessive oxidation product,and its effect on the regulation of neuropathic pain has not been confirmed.Our study was to evaluate the effects of mitochondria-targeted antioxidant on pain behaviors in neuropathic pain rats and its mechanismMethods 160 Male Sprague-Dawley rats,were randomly divided into 4 groups(n=40 each)using a random number table: sham operation group(group Sham),sham operation and mitochondrial antioxidant treatment group(group Sham and MT),neuropathic pain group(group NP),neuropathic pain and mitochondrial antioxidant treatment group(group NP +MT).Neuropathic pain was induced by chronic constriction injury (CCI)in NP and NP +MT groups.Starting from 7th day after operation,mito-tempo(triphenylphosphine cation combined with antioxidant)0.7 mg/kg in 1ml of normal saline was injected intraperitoneally once a day for 14 consecutive days in Sham+MT and NP+MT group,and the equal volume of normal saline was given once a day for 14 consecutive days in Sham and NP groups.On 1 day before operation and 3,7,14 and 21 days after operation,the mechanical paw withdrawal threshold(MWT)and thermal paw withdrawal latency(TWL)were measured.m PTP opening was detected by fluorescence quantitative method.Lumbar 4-6 segments of the spinal cord were harvested to detect the expression of TRPV1(by Western blot)before operation and on days 3,7,14 and 21 after operation.Results 1,MWT and TWL significantly reduced in neuropathic pain group after CCI.Mitochondria-targeted antioxidant can significantly relieve pain behaviors caused by CCI.2,Mitochondria-targeted antioxidant can significantly reduce m PTP excessive opening caused by CCI.3,Up-regulation of TRPV1 expression is related to pain behavior of neuropathic pain rats and mitochondria-targeted antioxidant can reverse the TRPV1 expression caused by chronic sciatic nerve injury.Conclusion Mitochondrial antioxidant can alleviate the pain behaviors caused by neuropathic pain.Its mechanism may be related to improve mitochondrial function and spinal TRPV1 expression.