Are We Paying a High Price for Surgical Sympathectomy? A Systematic Literature Review of Late Complications

The purpose of this article was to systematically review the literature in order to assess (1) the current indications for surgical sympathectomy and (2) the incidence of late complications collectively and per indication. All types of upper or lower limb surgical sympathectomies are included. An extensive search strategy looked for controlled trials and observational studies or case series with an english abstract. Out of 1,024 abstracts from MEDLINE and 221 from EMBASE, 135 articles reporting on 22,458 patients and 42,061 procedures (up to april 1998) fulfilled the inclusion criteria. Weighted means were used to control for heterogeneity of data. No controlled trials were found. The main indication was primary hyperhidrosis in 84.3% of the patients. Compensatory hyperhidrosis occurred in 52.3%, gustatory sweating in 32.3%, phantom sweating in 38.6%, and horner's syndrome in 2.4% of patients, respectively, with cervicodorsal sympathectomy, more often after open approach. Neuropathic complications (after cervicodorsal and lumbar sympathectomy) occurred in 11.9% of all patients. Compensatory hyperhidrosis occurred 3 times more often if the indication was palmar hyperhidrosis instead of neuropathic pain (52.3% versus 18.2%), whereas neuropathic complications occurred 3 times more often if the treatment was for neuropathic pain instead of palmar hyperhidrosis (25.2% versus 9.8%). Surgical sympathectomy, irrespective of approach, is accompanied by several potentially disabling complications. Detailed informed consent is recommended when surgical sympathectomy is contemplated.     

A prospective study of neuropathic pain induced by thoracotomy: incidence, clinical description, and diagnosis

This study evaluated prospectively the incidence of neuropathic pain after thoracotomy, described its clinical characteristics, and delineated landmarks for its diagnosis in daily practice. We evaluated clinically painful symptoms and sensory deficits in 54 patients after lateral/posterolateral thoracotomy for broncho-pulmonary carcinoma with standardized surgical and analgesic procedures. At 2 months, 49 patients suffered from non malignant thoracic pain, and at 6 months 38 patients (loss to follow-up for 7) reported persisting pain. In 35 patients, painful symptoms and sensory deficits could be evaluated using a standardized clinical bedside procedure. According to the grading system proposed by Treede et al. [41], neuropathic pain was considered probable in 21 patients, while use of the DN4 questionnaire concluded that neuropathic pain was probable in 17 patients. The two diagnostic procedures provided similar conclusions in 16 patients. Morphine consumption during the early post-operative period (mean 111.3 ± 30.8 mg/day) and pain intensity (VAS: mean 5.71 ± 2.1) were significantly higher in patients suffering from neuropathic pain than in other patients with pain (mean 80 ± 21.4 mg/day; VAS: mean 3.9 ± 2.4). The clinical picture in most patients with neuropathic pain included electric shocks and severe multimodal hypoesthesia in the sensory area of 5th/6th intercostal nerves. Thus, our results indicate a minimal incidence of chronic post-thoracotomy pain at 70% and that of neuropathic pain at 29%, this latter being clinically suggested by a combination of certain symptoms and reinforced by the DN4 questionnaire when sensory deficit at scar is present.     

Adrenergic sensitivity of the sensory receptors modulating mechanical allodynia in a rat neuropathic pain model

This study focuses on changes in adrenergic sensitivity in untransected sensory axons that innervate an area of skin made neuropathic by transection of neighboring nerves. The segmental nerve injury model is favorable for this since all axons in the L5 and L6 nerves are transected whereas the L4 axons are intact. Earlier findings are that pain behaviors develop after this injury and that these beahviors are ameliorated by sympathectomy. The present study shows that behavior indicating mechanical allodynia can be rekindled after sympathectomy by intradermal norepinephrine and -2 but not -1 adrenergic ligands and the rekindling can be blocked by -2 but not -1 adrenergic antagonists. By contrast neither intradermal norepinephrine nor other adrenergic agonists or antagonists have any demonstrable effects in the normal or after either neuropathic surgery or sympathectomy alone. These data suggest that the combination of neuropathic surgery and sympathectomy results in an upregulation of active -2 adrenergic receptors on the undamaged sensory axons that provide the remaining sensory innervation to a neuropathic area partially denervated by segmental nerve lesions. These changes on undamaged axons presumably compliment similar changes on the transected axons and, thus play a role in the development of neuropathic pain.     

Chronic pain and sensorimotor deficits following peripheral nerve injury

Following upper limb peripheral nerve transection and surgical repair (PNIr) patients frequently exhibit sensory and motor deficits, but only some develop chronic neuropathic pain. Thus, the sensorimotor outcome of PNIr may be impacted by individual factors. Therefore, our aims were to determine if patients with chronic neuropathic pain (PNI-P) following PNIr (1) are distinguished from patients without pain (PNI-NP) and healthy controls (HCs) by the psychological factors of pain catastrophizing, neuroticism or extraversion, and (2) exhibit more severe sensorimotor deficits than patients who did not develop chronic pain (PNI-NP). Thirty-one patients with complete median and/or ulnar nerve transection (21 PNI-NP, 10 PNI-P) and 21 HCs completed questionnaires to assess pain characteristics, pain catastrophizing, neuroticism and extraversion and underwent sensorimotor evaluation. Nerve conduction studies revealed incomplete sensorimotor peripheral recovery based on abnormal sensory and motor latency and amplitude measures in transected nerves. The patients also had significant deficits of sensory function (two-point discrimination and vibration, touch, and warmth detection), sensorimotor integration, and fine motor dexterity. Compared to PNI-NP patients, PNI-P patients had higher vibration detection thresholds, performed worse on sensory-motor integration tasks, had greater motor impairment, and showed more impaired nerve conduction. Furthermore, PNI-P patients had reduced cold pain tolerance, elevated pain intensity and unpleasantness during the cold pressor test, and they scored higher on neuroticism and pain-catastrophizing scales. These data demonstrate that chronic neuropathic pain following PNIr is associated with impaired nerve regeneration, profound sensorimotor deficits and a different psychological profile that may be predictive of poor recovery after injury.     

Persistent postsurgical pain in a general population: prevalence and predictors in the Tromsø study

Population-based data on the prevalence of persistent postsurgical pain are scarce. This study aimed to assess the prevalence of persistent postsurgical pain in a general population and to describe associated physical, social, and psychological factors, including symptoms of nerve injury and sensitization. A cross-sectional survey was performed in northern Norway with questionnaire items covering surgery, pain, and sensory abnormalities in the area of surgery. Of the 12,982 participants, 24.0% (3111) had undergone one or more surgical procedures during the 3 years preceding the survey. Of these, 2043 had the surgery performed more than 3 months before the investigation. Persistent pain in the area of surgery was reported by 40.4% of the patients (826 of 2043), moderate or severe pain by 18.3% (373 of 2043). Hypoesthesia, hyperesthesia, or both was reported by 24.5% (501 of 2043). There were strong associations between sensory abnormalities and persistent pain, increasingly with higher pain intensities; odds ratios were 2.68 for hypoesthesia and 6.27 for hyperesthesia. Of the 826 individuals reporting persistent pain in the anatomical area of surgery, 51.0% reported chronic pain when questioned without specific reference to the surgery. The present study supports evidence from clinical studies of persistent postsurgical pain, indicating a high prevalence, but reveals large discrepancies in report of pain, depending on the questions asked and the context in which the questions are presented. Strong associations between sensory abnormalities and pain indicate neuropathic mechanisms in a major proportion of cases.     

Neurophysiologic and quantitative sensory testing in the diagnosis of trigeminal neuropathy and neuropathic pain

This study investigated the utility of neurophysiologic examination and thermal quantitative sensory testing (QST) in the diagnosis of trigeminal neuropathy and neuropathic pain. Fifty-eight patients (14 men), 34 with sensory deficit within the inferior alveolar nerve (IAN) and 24 within the lingual nerve (LN) distribution, were included. Twenty-six patients (45%) reported neuropathic pain. Patients underwent blink reflex (BR) test and thermal QST; sensory neurography was done to the IAN patients. Results of clinical sensory testing were available from the charts of 48 patients revealing abnormal findings in 77% of the IAN and in 94% of the LN patients. The BR test was abnormal in 41%, neurography in 96%, and QST in 91% of the IAN patients. In the LN group, BR was abnormal in 33%, and QST in 100% of the patients tested. Neurophysiologic tests and QST verified the subjective sensory alteration in all but 2 IAN patients, both with old injuries, and 4 LN patients who did not undergo QST. When abnormal, thermal QST showed elevation of warm and cold detection thresholds (hypo/anesthesia), hypoalgesia was less marked, and heat allodynia was only occasionally present. Contralateral thermal hypoesthesia after unilateral injury was found in 14 patients. It was associated with the occurrence of neuropathic pain (P=0.016). Axonal Abeta afferent damage was less severe in the IAN patients with pain than in those without pain (P=0.012). Neurophysiologic tests and thermal QST provide sensitive tools for accurate diagnosis of trigeminal neuropathy and study of pathophysiological features characteristic to human neuropathic pain.     

A behavioral model of neuropathic pain induced by ligation of the common peroneal nerve in mice.

Different laboratory animal models of neuropathic pain that replicate pathophysiological changes in patients have been developed. In most animal models of neuropathic pain, both sensory and motor nerves are injured. Thus, animals usually show both abnormal sensory and motor responses. Assessment of the sensory system is likely to be affected by the motor defects, although motor functions have not been evaluated in previous neuropathic pain models. An ideal neuropathic pain model to assess behavioral nociceptive responses in animals is one without affecting motor function and without muscle injury. Here, we report a novel mouse model of neuropathic pain with normal motor functions. Ligation of the common peroneal nerve near the head of fibula was performed by a less invasive procedure. Long-lasting behavioral allodynia and thermal hyperalgesia was observed in mice after the ligation. Furthermore, behavioral allodynia is resistant to morphine treatment at 5 mg/kg body weight, as reported in some cases of neuropathic pain. Standard rotarod test analysis confirmed intact motor functions. Our results show that ligation of the common peroneal nerve can be used as an efficacious mouse model for assessing behavioral nociceptive responses in neuropathic pain. PERSPECTIVE: Tests to assess behavioral responses in a neuropathic pain model depend on intact motor functions. Here we report a less invasive procedure to ligate common peroneal nerve of leg to induce neuropathic pain with least motor defects.     

Pathogenesis of complex regional pain syndrome (CRPS)

Neuropathic pain results from injury to neural structures within the peripheral or central nervous systems. Such injury promotes spontaneous and ectopic firing of nerves as well as reorganization of the nervous system. Neuropathic pain persists chronically. Patients who suffer from neuropathic pain exhibit persistent or paroxysmal pain without apparent immediate cause or pain hypersensitivity after tissue damage. This hypersensitivity is manifest as hyperalgesia and allodynia. Complex regional pain syndrome, CRPS is a category of neuropathic pain and is further divided into type I(reflex sympathetic dystrophy: RSD) and type II(causalgia). CRPS is characterized by localized autonomic dysregulation in the affected area with vasomotor and/or sudomotor changes, edema, colour difference, sweating abnormality, and atrophy.     

Thoracoscopic sympathectomy for palmaris hyperhidrosis

INTRODUCTION: Palmaris hyperhidrosis is a disorder mediated by the sympathetic nervous system. It causes excessive sweating. This study evaluated the safety, efficacy, and outcome after thoracoscopic sympathectomy in patients with palmaris hyperhidrosis. METHODS: We reviewed the medical records of 18 patients (10 male) who underwent bilateral thoracoscopic sympathectomy between July 1998 and June 2001. RESULTS: The patients' mean age was 34 years. No conversions to thoracotomy occurred. Three 2- to 5 mm trocars were used.The thoracic sympathetic chain was resected from ganglia T2-T4, except in one patient with axillary hyperhidrosis requiring resection to T5. The mean operating time was 112 minutes, the mean blood loss was 50 ml, and the mean postoperative hospital stay was 1.2 days. Two patients had a unilateral pneumothorax requiring tube thoracostomy; one patient developed a chest wall hematoma at a trocar site that resolved without treatment, and one patient developed a transient unilateral Horner's syndrome. There have been no hospital readmissions. After a mean follow-up period of 14 months, 11 patients (56%) reported compensatory sweating. Sixteen patients (89%) were satisfied with their outcomes. One patient was dissatisfied because of excessive compensatory sweating, and another continues to have mild unilateral sweating on one hand and compensatory sweating of the face. CONCLUSION: Thoracoscopic sympathectomy is a safe and effective alternative treatment for palmaris hyperhidrosis. Compensatory sweating occurs in more than 50% of patients but is tolerable in most. The majority of patients are satisfied with their short-term outcomes.     

Effects of sympathectomy in a model of causalgiform pain produced by partial sciatic nerve injury in rats

In a previous report we presented a novel behavioral model of neuropathic pain disorders, produced in rat by a unilateral ligation of about half of the sciatic nerve. The model is characterized by rapid onset of behaviors suggesting spontaneous pain and disordered responses to non-noxious and noxious stimuli. These include reduced withdrawal thresholds to repetitive touch in the partially deafferented skin ('touched-evoked hyperesthesia'), touch-evoked allodynia, reduced withdrawal thresholds to noxious thermal stimuli and exaggerated responses to noxious heat and mechanical stimuli ('thermal hyperalgesia'). Some of these disorders are seen at mirror image sites on the hind limb opposite the lesion. These disorder start within hours after partial nerve injury, last many months and are very similar to causalgia in humans following partial nerve injury. Since sympathetic efferent activity is known to aggravate causalgia in humans and sympathectomy is known to relieve it, we studied the effect of changing sympathetic outflow in the rat model. Reversible sympathectomy was carried out using guanethidine injected intraperitoneally in 3 experiments, each at a different time in relation to the partial nerve injury. We found that: (1) sympathectomy performed several months postoperatively alleviated the sensory disorders bilaterally; (2) sympathectomy prior to nerve injury partially prevented the appearance of thermal hyperalgesia but did not affect hyperesthesia to repetitive touch; and (3) sympathectomy at the time of nerve injury aggravated the sensory disorders during the first few days. As maintenance and production of the sensory disorders in this animal model depended on sympathetic nervous outflow, we conclude that the rats were suffering from a syndrome analogous to sympathetically maintained causalgia in man.     

Central sensitization in carpal tunnel syndrome with extraterritorial spread of sensory symptoms

Extraterritorial spread of sensory symptoms is frequent in carpal tunnel syndrome (CTS). Animal models suggest that this phenomenon may depend on central sensitization. We sought to obtain psychophysical evidence of sensitization in CTS with extraterritorial symptoms spread. We recruited 100 unilateral CTS patients. After selection to rule out concomitant upper-limb causes of pain, 48 patients were included. The hand symptoms distribution was graded with a diagram into median and extramedian pattern. Patients were asked on proximal pain. Quantitative sensory testing (QST) was performed in the territory of injured median nerve and in extramedian territories to document signs of sensitization (hyperalgesia, allodynia, wind-up). Extramedian pattern and proximal pain were found in 33.3% and 37.5% of patients, respectively. The QST profile associated with extramedian pattern includes: (1) thermal and mechanic hyperalgesia in the territory of the injured median nerve and in those of the uninjured ulnar and radial nerves and (2) enhanced wind-up. No signs of sensitization were found in patients with the median distribution and those with proximal symptoms. Different mechanisms may underlie hand extramedian and proximal spread of symptoms, respectively. Extramedian spread of symptoms in the hand may be secondary to spinal sensitization but peripheral and supraspinal mechanisms may contribute. Proximal spread may represent referred pain. Central sensitization may be secondary to abnormal activity in the median nerve afferents or the consequence of a predisposing trait. Our data may explain the persistence of sensory symptoms after median nerve surgical release and the presence of non-anatomical sensory patterns in neuropathic pain.     

Chemical sympathectomy for neuropathic pain: does it work? Case report and systematic literature review.

OBJECTIVE: To determine if chemical sympathectomy successfully reduces limb neuropathic pain. DESIGN: Systematic literature review of the effectiveness of phenol or alcohol sympathectomy for extremity neuropathic pain. PATIENT: A 29-year-old female with complex regional pain syndrome of both lower extremities after back surgery who was submitted to bilateral lumbar chemical sympathectomy. SEARCH STRATEGY: The Cochrane Database of Systematic Reviews, the Cochrane Controlled Trials Register, Medline, and EMBASE were systematically searched. OUTCOME MEASURES: (1) For the patient in question: spontaneous pain, allodynia, pinprick hyperalgesia, pressure evoked pain; (2) For the literature review: meaningful versus nonmeaningful pain relief based on degree and duration (>2 weeks) of pain relief. RESULTS: (1) The case reported experienced partial temporary relief of pain primarily related to selective modulation of allodynia, but not deep pain or pinprick hyperalgesia; (2) 44% of 66 patients in 13 studies that met the authors' inclusion criteria experienced meaningful pain relief. Whereas 19% experienced no meaningful relief, for the remaining 37% of the patients no conclusions regarding duration and degree of relief could be drawn due to poor reporting of outcomes. CONCLUSIONS: Based on the case reported and systematic literature review, chemical sympathectomy seems to have at best a temporary effect, limited to cutaneous allodynia. Despite the popularity of chemical sympatholysis, only few patients and poorly defined outcomes are reported in the literature, substantiating the need for well-designed studies on the effectiveness of the procedure.     

Other Surgical Interventions

Abstract:   Optimal management of patients with chronic neuropathic pain requires a multidisciplinary approach that may include surgery. Yet despite the fact that lumbosacral spinal surgery, for example, is performed in thousands of patients every year, there is very little controlled clinical data to support its use or that of other surgical techniques in the treatment of chronic nonmalignant pain, especially neuropathic pain. Nevertheless, there is evidence of some success for ablative techniques such as dorsal root entry zone lesioning for phantom limb pain and girdle-zone neuropathic pain, and sympathectomy for the treatment of complex regional pain syndrome, and a variety of operations for tic douloureux. However, before considering a surgical procedure, a nonsurgical approach should have been tried and the suitability of the patient must be carefully assessed. To fully establish the role of surgery in the treatment of chronic neuropathic pain, further well-designed, prospective, controlled trials are essential.     

Systemic adenosine infusion reduces the area of tactile allodynia in neuropathic pain following peripheral nerve injury: a multi-centre, placebo-controlled study.

Systemic adenosine has been shown in earlier case reports and a small placebo-controlled study to reduce pathological sensory dysfunction such as tactile allodynia in neuropathic pain. To evaluate this further, the effects of systemic adenosine infusion (50 microg/kg/min for 60 min) on tactile sensory dysfunction and pain was evaluated in 26 patients suffering peripheral neuropathic pain characterized by dynamic tactile allodynia. A randomized, cross-over, double-blind, placebo-controlled technique was used in this multi-centre study.Psychophysical methods were used to evaluate sensory dysfunction and spontaneous pain. The area of dynamic tactile allodynia was significantly reduced by adenosine compared with placebo (p=0.043), but spontaneous pain and tactile pain threshold were not significantly improved compared with the effects of placebo treatment. As a secondary outcome, a higher incidence of positive subjective effects on the clinical pain condition, in a few cases with long duration (several months), following adenosine treatment was found when the global effect of respective treatment was assessed (p=0.028). The results demonstrate involvement of adenosine receptor-sensitive pain mechanisms in some aspects of the sensory dysfunction often found in neuropathic pain.     

Epidemiology of Refractory Neuropathic Pain

Abstract:   Although neuropathic pain can be acute in nature, in most patients the pain is persistent (or "refractory"). Patients with chronic neuropathic pain are seen most often in clinical practice. It consists of a number of different disease-specific indications, each of which can have differing diagnostic definitions and cutoffs. Consequently, it is difficult to estimate precisely the prevalence and incidence of neuropathic pain. The limited currently available epidemiological literature is reviewed in this article. The burden of neuropathic pain on patients and healthcare systems appears to be potentially large, with an estimated prevalence of 1.5%. Patients with neuropathic pain experience a poor health-related quality of life and consume a high level of healthcare resources, and costs. The future prioritization by healthcare policy makers for neuropathic pain treatment funding requires further data to clarify its epidemiology, the burden on the health of patients, and the demand on healthcare budgets.     

Complex Regional Pain Syndrome Type I: Neuropathic or Not?

Complex regional pain syndrome (CRPS) is clinically characterized by pain, abnormal regulation of blood flow and sweating, edema of skin and subcutaneous tissues, active and passive movement disorders, and trophic changes. It is classified as type I (reflex sympathetic dystrophy) and type II (causalgia). CRPS cannot be reduced to one system or to one mechanism only. In the past decades, there has been absolutely no doubt that complex regional pain syndromes have to be classified as neuropathic pain disorders. This situation changed when a proposal to redefine neuropathic pain states was recently published, which resulted in an exclusion of CRPS from neuropathic pain disorders. We analyzed the strength of the scientific evidence that supports the neuropathic nature of complex regional pain syndromes.     

胸锁乳突肌瓣预防腮腺切除术后味觉出汗综合征效果的Meta分析

目的采用Meta分析方法评估胸锁乳突肌瓣预防腮腺切除术后味觉出汗综合征的效果。方法计算机检索Cochrane图书馆、MEDLINE、EMbase、CBM、VIP、CNKI和WanFang Data中从建库至2012年3月收录的关于采用胸锁乳突肌瓣预防腮腺切除术后味觉出汗综合征的随机对照试验。由2位评价者独立对符合纳入标准的研究进行资料提取、质量评价并交叉核对后,采用RevMan 5.1软件进行Meta分析。结果最终纳入10个研究,共825例腮腺切除术患者。Meta分析结果表明:与空白对照组相比,采用胸锁乳突肌瓣可使腮腺切除术患者术后味觉出汗综合征主观发生风险显著降低78%[OR=0.22,95%CI(0.08,0.59),P=0.003],客观发生风险显著降低83%[OR=0.17,95%CI(0.05,0.60),P=0.006];敏感性分析显示上述结果稳定性好。基于GRADE系统的证据等级均为"低级"。漏斗图结果显示无明显发表偏倚。结论当前证据表明使用胸锁乳突肌瓣能显著降低腮腺切除术患者术后味觉出汗综合征的主观及客观发生率。但鉴于纳入研究的局限性,建议行更多大样本、高质量的随机对照试验,并将是否影响胸锁乳突肌功能作为结局指标之一做进一步论证。     

T2-4与T3-4交感神经链切断治疗手足多汗症术后代偿性出汗比较

目的:通过比较胸腔镜下T2-4与T3-4交感神经链切断治疗手足多汗症术后代偿性出汗发生情况,探讨其发生的可能机制.方法:手足多汗症患者146例,按不同手术方式分为T2-4组(行T2-4水平交感神经链切断术,共66例)与T3-4组(行T3-4水平交感神经链切断术,共80例).比较两组术后第1日、第6个月手术效果以及代偿性出汗发生部位和严重程度.结果:术后两组手汗治愈率100％,最常见代偿性出汗部位是背部和胸部.术后第1日T2-4组代偿性出汗发生率明显高于T3-4组(39％对比21％,P＜0.05),T2-4组出现2例重度代偿性出汗,T3-4组无重度者.术后6个月T2-4组代偿性出汗发生率依然明显高于T3-4组[24％ (16/66)对比11％ (9/80),P＜0.05].T2-4组仍有1例重度代偿性出汗患者.结论:降低胸交感神经链切断位置可减少代偿性出汗发生率和严重程度,T3-4切断术是一种较为理想的手术方式.代偿性出汗可能随时间有缓解趋势.     

The Lindblom roller.

Neuropathic pain is caused by injury of the peripheral or central nervous system. The neurological examination of the sensory system in neuropathic pain patients guides the anatomical localization of the injury. Among the sensory modalities to be tested, priority should be given to those subserved by small peripheral sensory fibers or by the spinothalamic tract that most commonly are abnormal in neuropathic pain patients. Testing of cold and warm perception was traditionally carried out in the clinic using tubes filled with water at different temperatures, a cumbersome method that has limited the routine examination of these sensory modalities. The Lindblom roller offers a practical and effective method of readily testing temperature perception and is among the best available clinical tools for delineating the anatomical boundaries of a sensory abnormality. Routinely use of the Lindblom roller shall be standard bedside clinical assessment of neuropathic pain patients. To exemplify this statement we describe two patients affected by complex and fluctuating painful sensory abnormalities caused by an extradural mass compressing the spinal cord. The level of the injury was readily localized with a roller kept at room temperature.