植入式脈衝射頻電刺激系統之研發於動物神經疼痛模型之可行性驗證

Abstract

傳統電刺激治療是利用數百赫茲與特殊波形的電刺激去干擾神經訊號，並進一步的開發植入式電刺激系統，讓這種刺激電流可以直接刺激中樞神經改善疼痛，但是這種技術需要頻繁持續刺激，衍生出電極阻抗變大、神經長時間刺激病變、止痛效果漸漸不佳等問題。而脈衝式射頻電刺激是目前介入性疼痛治療的一種方法，主要是利用脈衝式射頻電刺激去刺激神經傳導路徑上的神經元細胞以達到阻斷疼痛的目的，臨床上一次刺激止痛療程約可維持三到六個月療效，跟傳統電刺激的止痛原理不同，脈衝式電刺激是阻斷，而傳統電刺激是干擾，但是目前在文獻上對於疼痛與脈衝式高頻電刺激後止痛機轉尚有許多不清楚而有待釐清的問題。本研究是在結合臨床上所使用的脈衝式射頻電刺激與植入式裝置，利用工程設計方法建立適合植入裝置的刺激參數，達到安全有效的植入裝置仍有極大的發展空間。研究參考臨床單電極電刺激參數：單極電極加導電貼片、45伏特、射頻500KHz、刺激頻率 2Hz、脈波寬 20ms、刺激120秒；設計是用於植入式低電壓工作之實驗刺激參數：雙極電極、正負5伏特、射頻500KHz、 刺激頻率 2Hz 、脈波寬 25ms、 刺激5分鐘。並進一步進行動物實驗驗證此一參數的有效性與可行性。將老鼠分成控制組與實驗組(PRF)兩批進行神經結紮手術：，PRF組神經結紮後馬上進行刺激參數實驗，而控制組只放入電極不刺激，縫合後利用von Frey行為測試，觀察術後第三、五、八天的壓力疼痛閥值變化，比較兩批老鼠疼痛的差別驗證電刺激參數的止痛效果。 實驗結果發現控制組的老鼠神經結紮後，術後第三天平均只能耐受3.72克的力，而PRF組的老鼠術後第三天可接受9.10克，兩組做T-test所得P值>0.001，接受PRF後的老鼠可以承受的壓力大於控制組的壓力約2.45倍，具有顯著差異可以證明小電壓、雙極電極設計的PRF刺激在脊髓神經上的確具有止痛的效果。此研究實驗證明雙極電極、低功率、局部電流對比於臨床上單電極加導電貼片、高功率(45伏特)的設計能有顯著控制疼痛的效果，因為是雙極電極，電流只會再電極兩端流動，沒有導電貼片在刺激過程中掉落的風險，在DRG的應用可以有效改善SNL神經病變疼痛模型的老鼠行為並維持至少三天的止痛效果。

Conventional electrical stimulation used hundreds of hertz and special form of pulse to interfere with signal of nerve, and advanced technology was developing on implantable device, can stimulate directly on central nervous system and reduce intensity of pain, but this kind of stimulation need frequently use, and will cause impedance of electrode increase、nervous pathological changes after long-term stimulation、effect of release pain decrease and other phenomenon. Pulsed-radiofrequency stimulation(PRF) is one of main Interventional pain management (IVPM), using PRF stimulate the neurons on nervous pathway to block pain。In clinical application, one stimulation can maintain release pain for 3-6 months，but the mechanisms of conventional and PRF are different, conventional stimulation is interference, and PRF is block, so far the recent studies reported the mechanism of pain pathway and pain control by PRF is not clear，The present study is aimed at design of parameters of PRF stimulation for implantable device, and verification of feasibility and security of implantation。We designed PRF parameters, ±5 volts,500-KHz RF pulses, 25 milliseconds in duration. The pulses were delivered at 2Hz for a period of 5 minutes, to stimulate rat of pain model，The rats were randomly divided into two group：Control group and PRF group，PRF group were stimulated about mentioned parameter after spinal nerve ligation (SNL)，and Control group received same procedure as PRF group without PRF stimulation after SNL. von Frey behavior test was performed in both groups then. We observed the behavior change of 3rd、5th and 8th days after surgery, to verify the efficacy of PRF with the parameter we use . The Control group could tolerate the force of 3.72g at 3rd day after surgery, but PRF group could tolerate the force of 9.10g; which is significantly different ( P values <0.001). It proved the efficacy of PRF on pain control under the parameters we designed, whereby low power、local current through bi-polar electrode applied This research can prove the parameter of stimulation : bio-polar electrode、Low power(+5 ~ -5 volt)、local current，compare with clinical parameter：mono-polar electrode with pad、high power(45volt)， experimental parameter had effect of pain release，because electrode is bipolar type，current only flow between two tips of bipolar electrode，there is no risk that pad fall from skin during stimulation，furthermore application of PRF on DRG with experimental parameter can release pain on spinal nerve ligation (SNL) model of neuropathic pain model of rat, the effect can maintain at least 3days.