Spinal Cord Stimulation Alleviates Neuropathic Pain By Reducing TRPV1 Levels In Rats With Chronic Constrain Injury

Objective:Neuropathic pain(NP)is a kind of chronic pain,defined as"pain directly caused by injury or disease of the somatosensory nervous system".At present,drugs are still the main means of clinical treatment,but with many serious side effects,the treatment effect is not ideal.Spinal cord stimulation(SCS)is considered a promising minimally invasive nerve regulation method for the treatment of NP and has been widely used in clinical practice.To prove that SCS is an effective method for treating NP,it is important to understand the specific basic mechanism of SCS.Transient receptor potential vanilloid 1(TRPV1)is a ligand-gated non-selective cation channel,which can be activated by capsaicin,heat(≥43℃),low p H,protons,and other exogenous or endogenous substances,causing Ca2~+,Na~+,and other cations to enter the cell from outside the cell,thus triggering a series of biological effects.Many studies have proved that TRPV1 plays an important role in the development and maintenance of NP.Some studies have shown that TRPV1 positive small diameter peptidergic neurons can release pain-related neuropeptides such as substance P(SP)and calcitonin gene-related peptide(CGRP)and participate in the generation and transmission of pain.A previous study found that SCS can reduce the gene expression of TRPV1 and SP in T4 spinal cord segment in rats with intermittent myocardial ischemia to relieve angina pectoris,which indicates that SCS has a potential impact on the expression of TRPV1.In this paper,we aim to discuss whether SCS can alleviate chronic constriction injury(CCI)induced NP in rats by affecting the expression of TRPV1.Methods:Adult male SD rats weighing 280-320g were used to make the model.Rats’paw withdrawal threshold(PWT)was measured at 1,3,7,10,and 14 days after CCI,and the samples were taken at different time points.The protein expression of TRPV1 in the L4-6 spinal cord of rats was detected by Western blotting(WB).The spinal cord electrode was implanted into the epidural space of rats on the 8th day after CCI to establish the rat SCS model.From the 9th day,at 60Hz,250μm.The model of80Mo T was stimulated for 6 hours every day for 6 consecutive days.PWT was measured after the end of treatment every day.Finally,the protein expression of TRPV1,SP,and CGRP in the spinal cord of rats was detected with WB.Immunofluorescence staining(IF)was used to observe the expression of TRPV1changes in the spinal dorsal horn of rats.TRPV1 si RNA was injected into the sheath 7days after CCI,and the protein content of TRPV1,SP,and CGRP was detected by WB for 5 consecutive days.From the 4th day of SCS treatment,capsaicin was injected into the sheath every day before SCS treatment for three consecutive days,and PWT was recorded.The expression level of SP and TRPV1 in the spinal cord of rats was measured with WB.Results:(1)In the rat model of NP induced by CCI,the level of TRPV1 protein in the spinal cord increased.(2)SCS can alleviate mechanical hyperalgesia caused by CCI,reduce the level of TRPV1 protein in the spinal cord,and reduce the release of SP and CGRP in the spinal cord.(3)Intrathecal injection of TRPV1 si RNA can reduce the release of SP and CGRP in the spinal cord of CCI rats,thus reducing NP.(4)Intrathecal injection of low-dose capsaicin can reverse the analgesic effect of SCS,cause behavioral hyperalgesia in rats,and increase the release of SP and CGRP in the spinal cord.Conclusion:Spinal cord stimulation can alleviate neuropathic pain by inhibiting the expression of TRPV1 in the spinal cord of CCI model rats,reducing the release of SP and CGRP.