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Robert D. CardioVascular and Thoracic Surgery 9(2009)999-1002

Can chronic neuropathic pain following thoracic surgery be predicted during the postoperative period?. Robert D. CardioVascular and Thoracic Surgery 9(2009)999-1002. Introduction. 1.Chronic pain following thoracic surgery is common(> 50% ) 2. This pain has a significant impact on

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Robert D. CardioVascular and Thoracic Surgery 9(2009)999-1002

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  1. Canchronicneuropathicpainfollowingthoracicsurgerybepredictedduringthepostoperativeperiod?Canchronicneuropathicpainfollowingthoracicsurgerybepredictedduringthepostoperativeperiod? Robert D. CardioVascular and Thoracic Surgery 9(2009)999-1002

  2. Introduction 1.Chronic pain following thoracic surgery is common(>50%) 2. This pain has a significant impact on patient `s live(>40% report that pain is their Worst thing and it limited their daily live)

  3. The reason of the chronic pain following thoracic surgery The course is not fully understood But, intercostal nerve damage and subse- quent dysfunction has long been implicated intercostal nerve damage Pressure related to rib retraction Traction on the nerve

  4. The studies about the chronic neuropathic pain(CNP) Steegers et al. used a questionnaire to determine the incidence of CNP following Thoracic surgery,concluding 53% had neuropathic pain However,these studies wereretrospective postal surveysand with no information on the existence of neuropathic painbefore the operation

  5. The aim of the study 1.The incidence of ANP and CNP 2.hypothesized that the occurrence of ANP Would be associated with CNP characteristics at three months follow-up

  6. Methods Prospective ,observational cohort study Include Exclude Video assisted thoracic surgery Posterolateral thoracotomy Undergone VATS or thoracotomy Previously diagnosed neuropathic pain Pregnant

  7. Validated neuropathic pain screening tools 1.Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) 2. self-complete version(S-LANSS)

  8. LANSS Pain scale

  9. S-LANSSPain scale

  10. Include patients The day before scheduled surgery withdrawn LANSS score Positive LANSS scores 24h after regional or local anaesthetic infusion or injection had ceased postoperative Repeated the LANSS score Thosefailingtoreturnthe post were telephoned after a further two weeks and by telephone interview Three months following operation S-LANSS questionnaire LANSS or S-LANSS score >12 neuropathic

  11. Statistic 1.Relative risks between ANP and CNP with Fisher`s exact test 2.Any possible relationships between CNP and other factors using stepwise logistic regression analysis with the statistical package STATA

  12. Result The postoperative LANSS score was performed anaverage of 3 days following Surgery 87 of these 100 patients completed S-LANSS ,of these 87 patients, 19 (22%) had CNP 85 of the 100 patients completed the NRS, 53 (62%) had chronic pain,and of those patients18 (21%) had a pain score of between 5 and 10 on the NRS scale 87 of these 100 patients completed S-LANSS 19 (22%) had CNP 85 of the 100 patients completed the NRS 53 (62%) had chronic pain 18 (21%) had a pain score of between 5-10

  13. Result Hadasurgicallyplacedcatheter and continuous infusion of plain bupivicain eduring the postoperative period

  14. Result

  15. Result Item1,Does your pain feel like strange, unpleasant sensation in your skin? Words like prickling, tingling, pinsand needles was more predictive of 3 months CNP Patients with ANP were more likely to have CNP at 3 months than those without ANP [5/8(62.5%)vs17/79(18%) relative risk 3.5(95%CI 1.7-7.2)] Arelativeriskof4.5(95%CI 2.3-8.7)

  16. Patients with CNP had higher average LANSS scores during the postoperative period (median=7) than those who didn`t develop chronic pain (median=3, P=0.007 Mann- Whitney U-test) There was no correlation between CNP and gender,type of operation or whether the underlying disease diagnosis was malignant or benign

  17. Result Old patients were more likely to have CNP (P=0.04) No single analgesic technique was associated with the subsequent development of CNP.

  18. Result There was a correlation between the total postoperative LANSS score and the later three months S-LANSS total r-value of 0.33 (P>0.001) Patients with CNP (S-LANSS≧12) had higher NRS (medians5) than those with nociceptive pain (median=2, P=0.002 Mann-WhitneyU- test) at 3 months follow-up

  19. Discussion We found that 8% of patients under going thoracic surgery developed ANP in the immediate postoperative period and that 22% of patients have CNP 3 months after their operation

  20. Discussion Our results show a small but significant proportion of thoracic surgery patients have ANP characteristics and importantly that this predicts the development of CNP. However,3 patients with ANP didn`t develop CNP, suggesting that the natural history of ANP symptoms and signs may be that over a third of cases spontaneously resolve in the first three months

  21. Discussion The majority who developed CNP (74%) didn`t have NP in the immediate postoperative period, although they had significantly higher average LANSS scores. It is not clear whether this reflects a different pathophysiological process, or if it reflects a reduction in the sensitivity of the LANSS score when used in the early postoperative period.

  22. Discussion It has not been specifically designed for use in the early postoperative period. More work is needed to develop a validated tool to aid diagnosis of neuropathic pain in the immediate postoperative period

  23. Discussion Our study demonstrates that the presence of acute pain of predominantly neuropathic origin is significantly associated with development of CNP characteristics three months later

  24. 术后神经病理性疼痛 国际疼痛研究会（IASP）将这种由于外周或中 枢神经系统直接损伤功能紊乱引起的疼痛称为 神经病理性疼痛。 外周神经损伤引起的神经病理性疼痛，表现为 痛觉过敏，异常痛敏，感觉缺失和自发性疼痛。 其中中枢和外周敏化在神经病理性疼痛测产生 和维持中发挥重要的作用（Millar MJ-1999）。

  25. 神经病理性疼痛发生机制 1.外周机制 1.1 自发放电 1.2 离子通道表达的改变 1.3 P2X的作用 1.4 初级传入末梢的间接出芽 1.5 前炎症介质对伤害性感受器的敏化 多数的学者支持疼痛产生于受损伤的轴突和邻近的背根神经节传播来的异位冲动；有研究表明异常传入放电是感觉异常、感觉迟钝、和慢性神经病理性疼痛的重要原因 研究发现受损伤的神经纤维钠通道的重新分布对神经病理性疼痛的产生发挥重要的作用。因此钠通道是未来神经病理性疼痛治疗药物开发的重要靶点 P2X受体为配体门控离子通道，属于P2受体家族。P2X受体的配体是ATP，胞外ATP结合时P2X受体通道打开，允许阳离子(Na+、Ca2+等)通过。多种伤害性刺激均可引起细胞内释放ATP，ATP激活P2X受体引起疼痛。 外周神经损伤后，重新形成的轴突末梢可以在被切断神经的皮肤区域重新出芽，但这种出芽作用在术后神经病理性疼痛的发生中到底起何种作用，尚不完全明确。

  26. 神经病理性疼痛发生机制 2.中枢机制 2.1 神经病理性疼 痛的脊髓机制 2.2 神经病理性疼 痛的脊髓上机制 Aβ 纤维传入末梢出芽 NMDA受体作用 抑制性中间神经元作用 细胞因子的作用 中枢敏化 胶质细胞的作用 疼痛下行抑制系统的削弱和下行易化系统 的增强在中枢敏化的发生中起到一定的作 用；延髓腹内侧区（RAM）是下行易化系 统的上位中枢，外周神经损伤后其对脊髓 背角神经元的作用增强。

  27. 神经病理性疼痛诊断 神经病理性疼痛量表（ Neuropathic pain scale,NPS）包括10项疼痛描述符号（剧烈、尖锐、灼热、钝样、寒冷、敏感、不舒服、瘙痒、深部和体表），是精确有效的评估工具 。 1.病史和体格检查 2. NPS的疼痛性质 3.感觉异常、疼痛过敏、总和和感觉后效应 4. QST评估C纤维功能 定量感觉测量（Quantitative sensory testing，QST）：通过对冷和冷/痛以及热和热/痛的域值检测评估C纤维的功能

  28. 神经病理性疼痛药物治疗进展摘自2008第12届世界疼痛大会神经病理性疼痛药物治疗进展摘自2008第12届世界疼痛大会 三环类抗抑郁药能够减轻多发性神经病变患者的疼痛；且曲马多与多虑平联合用药具有协同效应；但其治疗作用需要一段时间体现。 1.抗抑郁药物 2.抗癫痫药物 3.局麻药 4.阿片类药物 5.非甾体类抗炎药物 新的抗癫痫药物加巴喷丁同其他抗癫痫和抗抑郁药物比较，副作用较小，效果确切。 局部利多卡因贴剂（Lidoderm）是FDA批准用于治疗神经痛的新药，无全身性副作用，具有广阔的应用前景 。 阿片类药物治疗急性疼痛效果明确，治疗神经病理性疼痛目前仍有争议，长期给予阿片类药物引起副作用也是限制其应用的原因之一。 Moini等认为CCI模型大鼠痛觉过敏和痛觉异常，是由于脊髓释放前列腺素和细胞因子所致。免疫细胞在慢性疼痛的产生和维持中起到了很大作用 。

  29. Thanks!!!

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