Capsaicin 8% Dermal Patch for Neuropathic Pain in a Pain Unit

AimsPain units manage approximately 20% of the patients with neuropathic pain, usually presenting with severe uncontrolled pain associated with substantial impairment of quality-of-life and disability. We aimed to analyze the experience with the capsaicin 8% dermal patch for managing patients with neuropathic pain in a pain unit.DesignThis was a post-authorization observational and retrospective study conducted at a single pain unit on patients with peripheral neuropathic pain under routine clinical care.MethodsDiagnosis of neuropathic pain was based on the Douleur Neuropathique 4 (DN4) questionnaire. Evaluations included pain intensity according to a visual analog scale and the quality-of-life as evaluated with the European Quality of Life-5 Dimensions (EQ-5D).ResultsWe included 66 patients with neuropathic pain lasting for a median of 24 months. The most frequent diagnosis was iatrogenic neuropathic pain (47%) and two thirds of patients exhibited extreme pain or discomfort. Pain intensity was reduced significantly from a mean (standard deviation [SD]) of 7.20 (1.95) at baseline to 6.02 (2.77) at month 3, leading to a mean change from baseline of 1.19 (95% confidence interval [CI], 0.59 to 1.78; p < .001; Cohen's d 0.49). The extent of the pain area was also significantly reduced from a median (interquartile range [IQR]) of 169.5 cm² (69.3-299.9) at baseline to 121.2 cm² (35.4-183.9) at month 3 (p < .001). There was an improvement in most dimensions of quality-of-life, especially regarding “usual activities,” “pain/discomfort,” and “anxiety/depression.” Tolerability was consistent with the known profile.ConclusionsOur results suggest that the capsaicin 8% dermal patch is a useful and well-tolerated treatment option for managing peripheral neuropathic pain in pain units.     

Capsaicin 8% topical patch (Qutenza)--a review of the evidence

Qutenza is a high-potency capsaicin (8%) topical patch, labeled for treating pain associated with postherpetic neuralgia (PHN). Qutenza decreases pain sensation by reducing transient receptor potential vanilloid 1 (TRPV1) expression and decreasing the density of epidermal nerve fibers in the application area. Systemic absorption from Qutenza is low. Qutenza has not been directly compared to any other medications for the treating PHN. Two pivotal clinical trials compared Qutenza to a control patch (0.04% capsaicin) in PHN. The primary endpoint of both trials was the reduction in numeric pain rating scale (NPRS) score. Qutenza reduced pain from baseline to weeks 2 to 8 (29.6% and 32% reductions) compared to control (19.9% and 24.4% reductions; P ≤ .01). The improvement in NPRS scores persisted, with score reductions greater with Qutenza (29.9% and 32.3% reductions) compared to control (20.4% and 25% reductions; P ≤ .03) for the period 2 to 12 weeks. Safety and efficacy of capsaicin 8% has been demonstrated in open-label trials for up to 48 weeks. The most common adverse drug reactions occurring with capsaicin 8% are application site erythema (63%) and application site pain (42%). Some patients experienced transient increases in blood pressure during Qutenza application. Qutenza must be administered by a physician or under the close supervision of a physician. Prior to application, pretreat the affected area with a topical anesthetic to reduce application site pain. Some patients may require systemic analgesics during and after treatment for treatment-associated pain. Applications of Qutenza can be repeated no sooner than once every 3 months, as needed.     

低频电穴位刺激对胃肠手术患者术后镇痛的效果

目的:探讨低频电穴位刺激对胃或直结肠切除术患者的术后镇痛作用并评价其效果。方法:ASAⅠ～Ⅱ级,行胃或直结肠切除术患者60例,随机分为低频电经皮穴位刺激(HANS)+患者静脉自控镇痛(PCIA)组(HANS组)和PCIA组(对照组)各30例,均于手术结束前30min缝合腹膜时给予托烷司琼3mg,曲马多1.5mg/kg静脉注射;在麻醉结束后5min,于复苏室(PACU)中开始使用PCIA镇痛。HANS组同时增加低频电穴位刺激30min。2组均于麻醉前5min、实施镇痛后30min检测血浆β-内啡肽(β-EP)的浓度,记录和评定术后的血压、呼吸、血氧饱和度和疼痛VAS评分,PCIA用量,有效和无效按压次数,镇痛和睡眠满意度,术后恶心呕吐(PONV)发生频率及程度。结果:术后血浆β-EP浓度与术前比较2组均升高,与对照组比较HANS组升高更明显(均P0.05)。术后HANS组0、2、6、14及24h的疼痛VAS评分、PCIA用量、有效及无效按压次数,均明显低于对照组;睡眠和镇痛满意度明显高于对照组(P0.05,0.01)。术后血压、呼吸、血氧饱和度及PONV发生频率和程度2组比较差异无统计学意义。结论:低频电穴位刺激可促进内源性β-EP的分泌,增强胃肠手术患者的术后镇痛效果。     

Capsaicin 8% Patch in Painful Diabetic Peripheral Neuropathy: A Randomized,Double-Blind,Placebo-Controlled Study

This 12-week study evaluated the efficacy and safety of capsaicin 8% patch versus placebo patch in painful diabetic peripheral neuropathy (PDPN). Patients aged 18 years or older with PDPN were randomized (1:1) to one 30-minute treatment (capsaicin 8% patch or placebo patch) to painful areas of the feet. Overall, 369 patients were randomized (capsaicin 8% patch, n = 186; placebo patch, n = 183). Percentage reduction in average daily pain score from baseline to between weeks 2 through 8 (the primary end point) was statistically significant for capsaicin 8% patch versus placebo (?27.4% vs ?20.9%; P = .025); improvements in pain were observed from week 2 onward. Versus placebo, patients treated with capsaicin 8% patch had a shorter median time to treatment response (19 vs 72 days) and modest improvements in sleep interference scores from baseline to between weeks 2 through 8 (P = .030) and weeks 2 through 12 (P = .020). Apart from application site reactions, treatment-emergent adverse events were similar between groups. No indications of deterioration in sensory perception of sharp, cold, warm, or vibration stimuli were observed. In patients with PDPN, capsaicin 8% patch treatment provided modest pain relief and sleep quality improvements versus a placebo patch, similar in magnitude to other treatments with known efficacy, but without systemic side effects or sensory deterioration.

地佐辛在剖腹产术后镇痛中的应用效果

目的探讨地佐辛在剖腹产患者术后硬膜外镇痛中的应用效果。方法 60例行剖腹产术的患者随机分为地佐辛组和芬太尼组。两组患者术后均行硬膜外镇痛,地佐辛组使用地佐辛+罗哌卡因+氟哌利多,芬太尼组使用芬太尼+罗哌卡因+氟哌利多。记录两组术后6、12、24和48h的视觉模拟法(VAS)评分,记录两组不良反应。结果两组术后各时间点VAS评分均无明显差异(P0.05),地佐辛组恶心、呕吐发生率明显低于芬太尼组(P0.05),其它不良反应则两组发生率无显著差异(P0.05)。结论地佐辛用于剖腹产术后镇痛效果好,不良反应少。     

开展镇痛教育对腹腔手术患者镇痛认知度及术后镇痛需求的影响

目的通过镇痛知识教育提高患者对术后镇痛的认知度，改善术后镇痛需求，有效控制术后疼痛。方法将168例择期腹腔手术患者按入院先后顺序随机分为实施镇痛教育组（观察组）和未实施镇痛教育组（对照组）各84例。对照组由责任护士在患者入院后一对一实施常规疼痛健康教育。观察组在对照组的基础上增加镇痛知识教育，统一教育内容，包括术后镇痛的临床意义、术后常用镇痛方法、镇痛方法优缺点、术后镇痛注意事项、止痛药的不良反应、』临床使用止痛药的常见误区，术前1d再次复述巩固教育内容。术前1d由责任护士用同一指导语进行问卷调查，评估患者对术后镇痛的认知度，术后2d内由责任护士询问和记录每位患者的不同镇痛需求。结果两组患者对镇痛的认知情况比较差异具有统计学意义。观察组患者对镇痛的临床意义、术后常用镇痛方法、镇痛方法优缺点、术后镇痛注意事项、使用止痛药的常见误区等知识的了解多于对照组（P〈0．005）。两组患者术后不同镇痛需求比较差异具有统计学意义，试验组患者术后使用PCA镇痛例数、肌内注射杜冷丁镇痛和口服止痛药的例数明显多于对照组（P〈0．005）。结论开展镇痛知识教育能显著提高患者对镇痛的认知度，提高患者术后镇痛的接受程度，改善患者术后镇痛需求，有效控制术后疼痛。     

静脉镇痛泵在剖宫产术后的应用效果分析

目的探讨静脉镇痛泵在剖宫产术后的临床应用效果。方法 300例剖宫产术后产妇按镇痛治疗方案分为对照组和观察组各150例。对照组给予盐酸哌替啶注射液肌肉注射镇痛,观察组给予曲马多静脉镇痛泵镇痛,观察比较两组产妇术后镇痛效果及泌乳状况。结果观察组术后镇痛效果优良率为94.7%,明显高于对照组的66.0%(P0.05)。与对照组相比,观察组24h内泌乳和哺乳次数10次的产妇例数明显增多,而泌乳不足的例数明显减少,比较都有统计学意义(P均0.05)。结论静脉镇痛泵是剖宫产术后有效的镇痛治疗方案,具有良好的镇痛效果,并可以促进产后泌乳,有利于母婴健康。     

Effect of Nitrous Oxide Analgesia on Pneumothorax

OBJECTIVE: To address whether spontaneous inhalation of 50% nitrous oxide (N2O) for up to 30 minutes adversely affects swine with pneumothorax (PNTX). METHODS: Five fasted, female swine (13-17 kg) were sedated with IV ketamine, intubated, and allowed to spontaneously inhale either 50% N2O or room air (RA) in a sequential crossover design in which each animal served as its own RA control. Small (group 1, 150 mL), medium (group II, 300 mL), and large (group III, 500 mL) PNTXs were created by instilling air into the left pleural space via an 18-Fr three-way Foley catheter. Changes in PNTX volume, heart rate (HR), central venous pressure (CVP), blood pressure (BP), ECG. and arterial blood gas (ABG) parameters were recorded in separate 10- and 30-minute trials. A 15-minute washout period was given between each trial. Data were analyzed using repeated-measures analysis of variance with post-hoc Tukey's tests. RESULTS: No significant increase in PNTX size was seen during the 10-minute trials. In the 30-minute trials, a statistically significant increase in absolute PNTX size was seen with N2O compared with RA for group I (44 +/- 17 vs 16 +/- 5 mL, p = 0.02), group II (61 +/- 21 vs 26 +/- 4 mL, p = 0.01), and group III (62 +/- 32 vs 40 +/- 5 mL, p = 0.06). No difference in HR, CVP, MAP, ABGs, or ECG were observed between the N2O and RA trials for any size PNTX. No animal developed hemodynamic signs of tension pneumothorax. CONCLUSION: In this model, spontaneous inhalation of 50% N2O for up to 30 minutes is associated with little risk of hemodynamic or respiratory compromise. Although PNTX size increases with 50% N2O use, the magnitude observed in this animal model is less than previously reported.     

大剂量辣椒素对兔肺神经肽类物质的影响

目的 研究大剂量辣椒素对兔肺P物质和降钙素基因相关肽（CGRP）的影响。方法 将16只成年健康雄性新西兰大白兔随机分为两组：载体组（A）、大剂量辣椒素组（B）。两组动物取样前7 d和前6 d分别于颈部皮下注射等量的载体或者辣椒素（20 mg/mL）。大剂量戊巴比妥钠静脉麻醉处死动物后立即切取左肺下叶,称重,匀浆,离心后取上清液置于-80℃冰箱保存待测P物质和CGRP。结果 A组肺组织中P物质的浓度高于B组（P〈0.05）,而CGRP的浓度两组差异无统计学意义（P＞0.05）。结论 大剂量辣椒素（100 mg/kg）不能完全耗竭兔肺初级感觉神经纤维的神经肽类物质。     

静脉及硬膜外自控镇痛的镇痛效应及对剖胸术后患者肺功能的影响

目的比较静脉自控镇痛（PCIA）与硬膜外自控镇痛（PCEA）的镇痛效果、副作用及对剖胸术后患者肺功能的影响。方法33例（ASAⅠ～Ⅱ级）食道癌择期手术患者随机分为两组；PCEA组（n=16）镇痛用药为吗啡（0．1mg／ml）＋布比卡因（0．125％）；PCIA组（n=17）镇痛用药为吗啡（1mg／ml）＋氟哌利多（0.1mg／ml）。测量术前及术后镇痛期间患者呼吸频率（RR）、潮气量（Vt）、肺活量（Vc）及脉搏氧饱和度（SpO2）；记录术后患者疼痛评分（VAS）及副作用。结果两组患者术后RR均明显快于术前（P〈0．01），而Vt、Vc及SpO2均较术前显著降低（P〈0.001），但各指标的组间差异均无显著性（P〉0．05）。PCEA组VAS评分明显低于PCIA组。尤其是在患者咳嗽和深呼吸时（P〈0．001）。结论剖胸术后PCEA镇痛效果明显优于PCIA，但对术后早期患者肺功能的影响两者相似。     

帕瑞昔布钠超前镇痛对开胸患者术后自控镇痛效果的影响

目的 观察帕瑞昔布钠超前镇痛对胸腔镜辅助开胸术后静脉自控镇痛(PCIA)效果的影响.方法 将60例ASA Ⅰ-Ⅱ级择期行胸腔镜辅助开胸术患者按随机数字表法分为3组:超前镇痛组(A组)20例于手术切皮前30 min静脉注射帕瑞昔布钠40 mg;常规镇痛组(B组)20例于手术缝皮时静脉注射帕瑞昔布钠40 mg;对照组(C组)20例不给予帕瑞昔布钠.3组患者术后均行曲马多静脉自控镇痛.分别记录术后1、2、4、8、12、24h的视觉模拟评分(VAS),记录术后24h内镇痛泵按压次数、有效按压次数、曲马多的用量及其不良反应发生率.结果 与C组比较,A组和B组术后1、2、4、8、12 h VAS评分,术后24 h内镇痛泵按压次数、有效按压次数,曲马多的用量及不良反应发生率均显著降低(P＜0.05).与B组比较,A组术后1、2、4、8、12 h VAS评分,术后24h内镇痛泵按压次数、有效按压次数,曲马多的用量及不良反应发生率均显著降低(P＜0.05).结论 帕瑞昔布钠于胸腔镜辅助开胸术超前运用,能减少术后PCIA曲马多用量,减轻不良反应的发生并提高镇痛效果.     

Affective Analgesia Following Muscarinic Activation of the Ventral Tegmental Area in Rats

Cholinergic stimulation of dopamine neurons in the ventral tegmental area (VTA) underlies activation of the brain reward circuitry. Activation of this circuit is proposed to preferentially suppress the affective reaction to noxious stimulation. Vocalization afterdischarges (VADs) are a validated model of the affective response of rats to noxious tail shock. The antinociceptive action of the acetylcholine agonist carbachol microinjected into the VTA on VAD threshold was compared with its effect on the thresholds of other tail shock–elicited responses (VDS, vocalizations during shock; SMR, spinal motor reflexes). Whereas VADs are organized within the forebrain, VDSs and SMRs are organized at medullary and spinal levels of the neuraxis, respectively. Carbachol (1 μg, 2 μg, and 4 μg) injected into VTA produced dose-dependent increases in VAD and VDS thresholds, although increases in VAD threshold were significantly greater than increases in VDS threshold. Administration of carbachol into VTA failed to elevate SMR threshold. Elevations in vocalization thresholds produced by intra-VTA carbachol were reversed in a dose-dependent manner by local administration of the muscarinic receptor antagonist atropine sulfate (30 μg and 60 μg). These results provide the first demonstration of the involvement of the VTA in muscarinic-induced suppression of pain affect.PerspectiveCholinergic activation of the brain reward circuit produced a preferential suppression of rats' affective reaction to noxious stimulation. The neurobiology that relates reinforcement to suppression of pain affect may provide insights into new treatments for pain and its associated affective disorders.     

Differential Effect of Capsaicin Treatment on Pain-Related Behaviors After Plantar Incision

We evaluated the effect of infiltration of dilute solutions of capsaicin, administered before plantar incision, on 3 pain-related behaviors: guarding pain, heat-withdrawal latency, and mechanical-withdrawal threshold. Perineural application of capsaicin was also studied and the appearance of the wound was also evaluated. Dilute solutions of capsaicin .025% and .10% were infiltrated in the plantar region 1 day before incision. In another group of rats, perineural capsaicin (1%) was applied to the nerves innervating the plantar aspect of the rat hindpaw. Rats were then tested for pain-related behaviors before and after plantar incision and then daily thereafter. Wound appearance was graded and histopathology was evaluated. Infiltration with capsaicin reduced guarding pain and heat hyperalgesia after plantar incision; there were minimal effects on mechanical responses. Perineural-capsaicin application produced a similar result. Both capsaicin infiltration and perineural-capsaicin application impaired wound apposition. Histologic evaluation also confirmed impaired wound apposition after capsaicin infiltration. In conclusion, dilute solutions of capsaicin have differential effects on pain-related behaviors after plantar incision. Based on the antinociception produced by capsaicin both via infiltration and perineural injection, the effect on wound appearance was likely related to its inhibitory effects on pain behaviors and was not necessarily a local effect of the drug.PerspectiveThis study demonstrated that capsaicin infiltration before plantar incision produced an analgesic effect that depended upon the stimulus modality tested. When evaluating novel treatments for postoperative pain, studies using a single stimulus modality may overlook an analgesic effect by not examining a variety of stimuli.     

芬太尼透皮贴剂用于分娩镇痛的效果观察

目的观察芬太尼透皮贴剂用于分娩镇痛的临床效果。方法选取我院2010年6月～2012年6月收治的ASAⅠ级经阴道分娩的足月初产妇160例作为研究对象,按照随机数字表法并经患者知情同意随机分为观察组与对照组各80例,观察组给予芬太尼透皮贴剂肾俞穴黏贴,对照组不给任何镇痛措施。比较两组患者的镇痛效果。结果 (1)两组产妇宫缩时间、产程时间及胎心率比较均无明显差异(P>0.05),无统计学意义。(2)观察组镇痛后较镇痛前有明显差异(P<0.05),对照组镇痛后活跃期及第二产程与镇痛前有明显差异(P<0.05),两组产妇镇痛前无明显差异(P>0.05),镇痛后比较均有显著差异(P<0.05),具有统计学意义。(3)两组产妇均未见明显并发症情况。结论应用芬太尼透皮贴剂穴位黏贴可以有效的降低分娩疼痛程度,且对宫缩、产程及胎心率均无明显影响,安全性较高,值得推广应用。     

Preservation of Acute Pain and Efferent Functions Following Intrathecal Resiniferatoxin-Induced Analgesia in Rats

Resiniferatoxin (RTX) is a potent agonist of TRPV1, which possesses unique properties that can be utilized to treat certain modalities of pain. In the present study, systemic intraperitoneal (i.p.) administration of RTX resulted in a significant decrease in acute thermal pain sensitivity, whereas localized intrathecal (i.t.) administration had no effect on acute thermal pain sensitivity. Both i.p. and i.t. administration of RTX prevented TRPV1-induced nocifensive behavior and inflammatory thermal hypersensitivity. There were no alterations in mechanical sensitivity either by i.p. or i.t. administration of RTX. In spinal dorsal horn (L4-L6), TRPV1 and substance P immunoreactivity were abolished following i.p. and i.t. administration of RTX. In dorsal root ganglia (DRG), TRPV1 immunoreactivity was diminished following i.p. administration, but was unaffected following i.t. administration of RTX. Following i.p. administration, basal and evoked calcitonin gene-related peptide release were reduced both in the spinal cord and peripheral tissues. However, following i.t. administration, basal and evoked calcitonin gene-related peptide release were reduced in spinal cord (L4-L6), but were unaffected in peripheral tissues. Both i.p. and i.t. RTX administration lowered the body temperature acutely, but this effect reversed with time. Targeting TRPV1-expressing nerve terminals at the spinal cord can selectively abolish inflammatory thermal hypersensitivity without affecting acute thermal sensitivity and can preserve the efferent functions of DRG neurons at the peripheral nerve terminals. I.t. administration of RTX can be considered as a strategy for treating certain chronic and debilitating pain conditions.

Perspective

Localized administration of RTX in spinal cord could be a useful strategy to treat chronic debilitating pain arising from certain conditions such as cancer and at the same time could maintain normal physiological peripheral efferent functions mediated by TRPV1.     

硬膜外镇痛用于剖宫产术后的观察

探讨剖宫产术后采用硬膜外镇痛的镇痛效果,对产妇及新生儿呼吸、循环的影响及其副反应,以便采取相应的护理措施.随机选择107例产妇作为实验组,于剖宫产结束时留置硬膜外导管,连接注有生理盐水100 ml,吗啡5 mg,氟呱啶5 mg,布比卡因45 mg的自控镇痛泵.101例产妇作为对照组,术后予曲马多塞肛.结果显示,实验组术后Ⅰ级镇痛达76.6%.与对照组比较,P＜0.01,有显著意义.对产妇及新生儿呼吸,循环比较P＞0.05.     

硬膜外镇痛用于剖宫产术后的观察

探讨剖宫产术后采用硬膜外镇痛的镇痛效果,对产妇及新生儿呼吸、循环的影响及其副反应,以便采取相应的护理措施。随机选择107例产妇作为实验组,于剖宫产结束时留置硬膜外导管,连接注有生理盐水100ml,吗啡5mg,氟呱啶5mg,布比卡因45mg的自控镇痛泵。101例产妇作为对照组,术后予曲马多塞肛。结果显示,实验组术后1级镇痛达76．6％。与对照组比较,P＜0．01,有显著意义。对产妇及新生儿呼吸,循环比较P＞0．05。     

氯诺昔康超前镇痛对应激的影响

【目的】观察氯诺昔康超前镇痛对应激的影响。【方法】选择40例因肝内外胆管结石拟行“T”管引流术或肝叶切除术患者,每组20例,随机分为L和H组,L组于麻醉前静脉滴注氯诺昔康8mg,H组术毕即刻静脉滴注氯诺昔康8mg,术后均以芬太尼行静脉给药病人自控镇痛（PCIA）。两组患者麻醉前、术毕0、6、24h四个时点各抽取外周静脉血8mL,测定血清C反应蛋白（CRP）、皮质醇（COR）、血糖（BS）。【结果】L组在选定时段CRP、COR、BS均显著低于H组（P〈0．05）。【结论】氯诺昔康术前较术后使用能更有效抑制应激反应。