| Background: Various surgical procedures such as thoracoabdominal aneurysms(TAAA) and endovascular aortic repair(EVAR), frequently transient block theaorta, evoke spinal ischemia-reperfusion injury following the initial surgery. Bvitamins have been demonstrated to be effective in treating chronic pain due toperipheral nerve injury.Objective: Our present study were to produce a novel central neuropathic painanimal model, further investigate the central neuropathic pain(NP) mechanisminduced by spinal cord ischemia/reperfusion injury (SCII). We investigated whetherB vitamins could alleviate neuropathic pain and reduce neuron injury followingtemporary ischaemia in a rat SCII model.Materials and Methods: This study describes a new rat model of centralneuropathic pain evoked by spinal unilateral ischemia and reperfusion injury, akinto a clinical procedure. SCII was produced by transiently blocking the unilaterallumbar arteries in adult male Sprague-Dawley rats. Behavioural and neurochemicalsigns of neuropathic pain and spinal neuron injury were analysed with and without B vitamin treatment. Vitamin B complex (VBC) containing thiamine(B1),pyridoxine (B6) and cyanocobalamin(B12)(B1/B6/B12at33/33/0.5mg/kg, i.p.,)immediately after surgery was repetitive administrated and then once daily for aconsecutive7-14days. The locomotor function of hindpaw was scored by BBB score(Basso DM, Beattie MS, Bresnahan JC). Thermal pain was determined by pawwithdrawal to radiant heat. Mechanical hyperalgesia was assessed with anElectronic von Frey Anesthesiometer. Western blotting (WB) was used to detect theexpression of proteins in spinal cord induced by SCII. Morphological changeswithin SCII were examined by Nissl staining and immunofluorescence staining. Thelevel of wnt gene expression was assessed by Real time-PCR (RT-PCR) technology.Results: The behavior detection of SCII surgerial rats exhibited clearly thermalhyperalgesia and mechanical allodynia in the ipsilateral side paw while thecontralateral side of paw did not change. And the BBB score show that locomotorfunction of SCII rat lost once time within24hour of ischemia/reperfusion and thenregain normal function in the following day. VBC significantly alleviates thermalhyperalgesia and does not work on the mechanical allodynia. SCII increase theexpression of glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptormolecule1(IBa1), P2X purinoceptor4(P2X4), the transient receptor potentialvanilloid subtype1/Vanilloid Receptor(TRPV1/VR1), increased progressively andreached peak at7/14days after SCII while β-Ⅲtubulin and GAD65(glutamic aciddecarboxylase65) decreased progressively up to14/21days. Repetitive treatment ofB vitamins significantly suppressed expression of GFAP, P2X4, VR1and c-FOS inSCII while B vitamins significantly increased β-Ⅲtubulin and GAD65level. SCIIcaused behavioural thermal hyperalgesia and mechanical allodynia andneurochemical alterations, including increased expression of the vanilloid receptor1(VR1) and induction of c-Fos, as well as activation of the astrocytes and microglialcells in the spinal cord. Repetitive systemic administration of vitamin B complex(B1/B6/B12at33/33/0.5mg/kg, i.p., daily, for7–14consecutive days) significantlyreduced thermal hyperalgesia and the increased expression of VR1and c-Fos, as well as activation of the astrocytes and microglial cells. SCII caused a dramaticdecrease of the expression of the rate-limiting enzyme glutamic aciddecarboxylase-65(GAD65), which synthesizes γ-aminobutyric acid (GABA) in theaxonal terminals, and β-III-tubulin, and also caused loss of Nissl bodies in thespinal cord. These alterations were largely prevented and rescued by the B vitamintreatment.The RT-PCR results show that the gene express level of wnt5a, wnt7a, wnt8bdecrease obviously after spinal cord ischemia reperfusion1day, and increase at3days and7days of reperfusion, while wnt1, wnt2, wnt5b show little change afterischemia/reperfusion.Conclusion: These findings demonstrate we produced a novel neuropathic painanimal model by SCII; Astrocytes of spinal cord may play a key role not only inmaintaining the neuropathic pain process induced by SCII, but also in the initialstage. Microglia may not only act as a doorkeeper role in the initial stage of SCII,but also facilitate the neuropathic pain initiation induced by SCII. The WNTpathway may play a key role in the neuropathic pain process induced by SCII.These findings support the idea that the B vitamins are capable of neuroprotectionand antinociception during spinal cord injury due to temporary ischaemia.Rescuing the loss of inhibitory GABAergic tone may reduce spinal centralsensitization and contribute to B vitamin-induced analgesia and suggest possibleclinical utility of B vitamins in aiding in neuropathic pain treatmen... |
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