| Neuropathic pain(NP)is a kind of chronic pain,which is caused by injury or disease of the somatosensory system,involving the peripheral and central somatosensory system,and the structure or function of these systems also changed.NP is one of the difficults of clinical pain treatments,has a serious threat to the patient’s physical and mental health.The increase of reactive oxygen species production,and the removement of ROS reduced,the imbalance of redox,oxidative stress were induced by nerve damage,which is a pathogenesis of NP.Mitochondria are the main source of free radicals,but also the attack target of free radicals.The excessive free radicals produced after nerve injury cause the oxidative stress,abnormal of structure and function in mitochondria,result in mitochondrial energy production reduced.It was found that mitochondrial-targetd antioxidant can be effective absorbed by mitochondria,and relief the mitochondrial oxidative stress effectivly.But the specific mechanism is not clear.The study is animal experiments which observe the therapy effect and mechanism of mitochondrial-targetd antioxidant to the chronic constrictive injury rat.Objective:.We study the treatment of mitochondrial-targetd antioxidant MitoTempo to the CCI rat model.To study the therapeutical effects of mitochondrial-targetd antioxidant on neuropathic pain model rat and its mechanism.Methods:Take 50 adult famale sprague dawley rats,by using the random number table,SD rats were divided into five groups(n=10): Sham group,Chronic constrictive injurygroup(CCI group),CCI+MitoTempo(0.7mg/kg),CCI+MitoTempo(0.35mg/kg)and CCI+MitoTempo(0.1mg/kg).The behavioristics,mechanical pain threshold,thermal pain threshold was detected to measure the treatment effect of MitoTempo.Mn-superoxide dismutase(MnSOD)activity,malonaldehyde(MDA)content and activity of glutathione(GSH)were detected by colorimetric method.The ultrastructure changes of mitochondria in dorsal root ganglion and dorsal horn was detected by electron microscopic.The content and location of dynamin-related protein 1(DRP1),Mitochondrial fission 1 protein(Fis1),Mitochondria fusion protein 1(Mfn1)and Optic atrophy protein 1(OPA1)were determined by Western Blotting and immunohistochemical.Results:MitoTempo can reduce the mechanical pain threshold and thermal pain threshold(P<0.05),improve the activity of MnSOD and GSH(P<0.05),decrease the content of MDA(P < 0.05),and the optimum concentration is 0.7mg/kg(P < 0.05).After the treatment of MitoTempo,mitochondrial membrane structure recovery to some extent,and with the increase of the concentration,the recovery extent of membrane structure increase;the content of DRP1 and Fis1 were down-regulated,but Mfn1 and OPA1 were up-regulated.Explain MitoTempo can inhibit the abnormal division,promote the integration of mitochondria,maintain the normal function of mitochondria.Conclusion:Above all,mitochondrial-targetd antioxidant has the effect of treatment to neuropathy pain,the potential mechanism is: it can decrease the level of oxidative stress caused by nerve damage,improve the structure of the damaged parts of mitochondrial,and inhibit the abnormal division,promote the normal integration of mitochondrial.Postherpetic neuralgia(PHN)is typical and clinically common NP,which is also a sensory nervous system injury-based neuropathic pain,caused by the herpes zoster virus.PHN is a persistent burning and paroxysmal stimulation pain that lasts from several months to several years.It commonly occurs in the chest and back,but may also affect the whole body.The pathogenesis of PHN has yet to be fully clarified,but most studies suggest that the herpes zoster virus located in the dorsal root ganglion is reactivated in people in old age(age ≥60 years,especially ≥80 years)or people with lowimmunity(e.g.,cachexia and cancer patients),thereby leading to the degeneration of the spinal nerve sensory system and increased neuropathic pain.At present,most of the clinical applications on neuropathic pain patients consisted of the antiviral treatment of early onset herpes zoster.For patients with persistent pain,a combination of multiple medications is used,these drugs have achieved good results to some extent,but their individual differences are large and cause many adverse reactions.Vitamin C is an immune relevant micronutrient,which is depleted in viral infections and this deficiency seems to play a critical role in the pathogenesis of herpes infections and in the development of postherpetic neuralgia.The objective of this observational study was to evaluate the relational pain and the incidence rate of PHN,which is based on conventional therapy and intravenously administrated vitamin C in patients with shingles.Objective:.Observe the therapy effect of vitamin C on acute herpes zoster associated pain and the influence to postherpetic neuralgia.Methods:30 outpatients who had acute zoster associated pain were randomized divided into control group and vitamin C group.The two groups were administrated common treatment,patients in vitamin C group were intravenously injected with 2.5g vitamin C on the first,third,and fifth days.Observe and record:the visual analogue scale of the two groups at pretreatment and 1w,2w,3w,4w aftertreatment,the visual analogue scale1 h,6h,12 h after intravenously injected with 2.5g vitamin C;the mechanical threshold,hyperalgesia,allodynia before and after therapy;the herpes healing time and the incidence rate of postherpetic neuralgia.Results:After treatment,the mechanical threshold of all patient had raised(P<0.01),the incidence rate of hyperalgesia and allodynia had decreased(P<0.05),but there were no statistical significance between two groups(P>0.05).The visual analogue scale had decreased after treatment of two group(sP<0.05).After intravenously injected with 2.5g vitamin C,the visual analogue scale of intermittent shooting pain and constant aching pain have had descend.Compared with control group,the incidence rate of postherpetic neuralgia had descended.Conclusion:In the condition of basic therapy,it could alleviate the acute zoster pain after using vitamin C.Compared with control group,the intermittent shooting pain had relieved obviously,the visual analogue scale and the incidence rate of postherpetic neuralgia had descended.The study did not prove any statistically significant effect of vitamin C in raise mechanical threshold and decrease incidence rate of hyperalgesia and allodynia. |
