Sympathectomy for neuropathic pain.

BACKGROUND: Neuropathic pain is defined as pain initiated or caused by a primary lesion or dysfunction in the nervous system. Some examples of this condition are phantom limb pain, post-stroke pain and complex regional pain syndrome type I (reflex sympathetic dystrophy) and type II (causalgia). Treatment options include drugs, physical treatments, surgery and psychological interventions. The concept that many neuropathic pain syndromes, particularly RSD and causalgia are "sympathetically maintained pains" has historically led to attempts to temporarily or permanently interrupt the sympathetic nervous system. Chemical sympathectomies use alcohol or phenol injections to destroy the sympathetic chain, but this effect is temporary until regeneration of the sympathetic chain occurs. Surgical ablation can be performed by open removal or electrocoagulation of the sympathetic chain, or minimally invasive procedures using stereotactic thermal or laser interruption. OBJECTIVES: The review aimed to assess the effects of both chemical and surgical sympathectomy for neuropathic pain. Secondary objectives were to compare the effects of sympathectomy with no treatment, placebo or conventional treatment, and to evaluate whether the technique of sympathectomy influences the outcomes of the procedure. SEARCH STRATEGY: We searched MEDLINE and EMBASE up to February 2003 and the latest issue of the Cochrane Library (Issue 1, 2003). We screened references in the retrieved articles, literature reviews and book chapters. We also contacted experts in the field of neuropathic pain. SELECTION CRITERIA: Clinical trials and observational studies assessing the effects of sympathectomy (surgical or chemical) for neuropathic pain of both central or peripheral origin were included. DATA COLLECTION AND ANALYSIS: Two reviewers applied the selection criteria to titles and abstracts. Full articles of potentially eligible trials were obtained and the same reviewers applied the inclusion criteria to the studies. The methodological quality of the studies was evaluated. The studies were also evaluated for clinical relevance according to a classification developed by our group. Statistical pooling was not possible due to heterogeneity of data; instead a narrative description of each included study was performed. MAIN RESULTS: We included four studies. One randomized trial comparing radiofrequency sympatholysis with phenol sympathectomy was rated as low methodological quality and it showed that radiofrequency sympatholysis does not offer advantage over phenol techniques. However, a modified technique produced sympatholysis comparable to that produced by 6% phenol, with less incidence of post-sympathectomy neuralgia. REVIEWER'S CONCLUSIONS: The practice of surgical and chemical sympathectomy is based on poor quality evidence, uncontrolled studies and personal experience. Furthermore, complications of the procedure may be significant, in terms of both worsening the pain or producing a new pain syndrome; and abnormal forms of sweating (compensatory hyperhidrosis and pathological gustatory sweating). Therefore, more clinical trials of sympathectomy are required to establish the overall effectiveness and potential risks of this procedure.

Unexplainable nondermatomal somatosensory deficits in patients with chronic nonmalignant pain in the context of litigation/compensation: a role for involvement of central factors?

OBJECTIVE: To address the prevalence and characteristics of nondermatomal somatosensory deficits (NDSD) in subjects with chronic pain in the context of compensation/litigation. METHODS: Data were collected via standardized history, examination, and patient- as well as physician-drawn body maps in a consecutive series of 194 subjects seen for the purpose of an independent medical examination. RESULTS: Forty-nine subjects (25.3%) with primarily widespread pain (often diagnosed as fibromyalgia) presented with hemisensory or quadrotomal deficits to pinprick and other cutaneous stimuli on the side of lateralized pain or worse pain. The NDSD limbs often had impairment of vibration sense (not infrequently associated with "forehead vibration split"), reduced strength, dexterity or movement, and extreme sensitivity to superficial skin palpation or profound insensitivity to deep pain. Spatial, temporal, qualitative, and evolutionary patterns of NDSD emerged associated with cognitive/affective symptoms. NDSD subjects were more often born outside Canada, more likely to be injured at work, present with abnormal pain behavior, and have negative investigations. CONCLUSION: NDSD are a prevalent problem associated with chronic pain. Future research should explore the prevalence of NDSD in other pain populations, the role of personality and related factors, and the underlying biological substrate of these deficits.

Gabapentin for neuropathic pain: systematic review of controlled and uncontrolled literature.

OBJECTIVE: To assess the efficacy/effectiveness and side effects of gabapentin for the treatment of neuropathic pain. DESIGN: Systematic review of the literature. METHODS: Extensive search of several electronic databases located both controlled and uncontrolled studies. Efficacy was assessed through meta-analysis of randomized controlled trials (RCTs), whereas the effectiveness of gabapentin in uncontrolled studies was assessed via a novel system of dichotomous classification of "bad" versus "good" results. FINDINGS: Thirty-five papers involving 727 patients with multiple neuropathic pain conditions met the inclusion criteria. The meta-analysis of the 2 high-quality, placebo-controlled RCTs showed positive effect of gabapentin in diabetic neuropathy and post-herpetic neuralgia. The addition of 2 low-quality, placebo-controlled RCTs did not alter the magnitude or direction of observed effect. The uncontrolled studies demonstrated positive effect on pain in different neuropathic syndromes, as well as benefit on different types of neuropathic pain; highest dose administered and rate-of-dose escalation showed wide variability between prescribers. Fewer and less severe side effects were reported in the uncontrolled studies. CONCLUSIONS: Gabapentin seems to be effective in multiple painful neuropathic conditions. The variable prescribing patterns of the uncontrolled studies raise the suspicion that effectiveness may be reduced if one limits administration of the drug to very low doses, whereas rapid dose escalation may be associated with increased central nervous system side effects. Well-designed controlled trials may provide insight into differential symptom sensitivity to the drug.

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.

Neuropathic pain syndrome as an occult manifestation of injury of the spinal cord after surgical repair of aortic coarctation.

Injury to the spinal cord injury with paraplegia, is a rare complication of surgical repair of aortic coarctation recognized immediately post-operatively. We present the case of a 41-year-old male undergoing surgery for restenosis at the site of a repair. Intra-operatively, he suffered inadvertent injury to an intercostal arterial branch during isolation of the aorta below the graft. Over the following months, he developed unusual symptoms involving the legs and genitourinary tract which, only after extensive investigations, were attributed to ischemic damage to the spinal cord related to the surgery. We suspect that similar syndromes reflecting injury to the spinal cord injury may be unrecognized following surgical repair of coarctation.

Anterior intercostal nerve damage after coronary artery bypass graft surgery with use of internal thoracic artery graft.

BACKGROUND: The prevalence of intercostal nerve damage associated with coronary artery bypass graft-internal thoracic (mammary) artery surgery is unknown. METHODS: A total of 37 consecutive patients with coronary artery bypass graft surgery (all with left internal thoracic artery graft) who were attending a cardiac-related exercise program underwent a thorough examination. Nerve damage was considered to be "definite" in the presence of two consistent and well-demarcated sensory abnormalities over the anterior chest wall within the T1 to T6 anterior intercostal nerve territory, and was considered "possible" in the presence of one such abnormality. RESULTS: Definite nerve damage was detected in 73% of the subjects, and possible nerve damage was found in another 11% at the site of internal thoracic artery harvesting. Protracted postoperative pain or unpleasant sensations, usually subsiding by 4 months, were reported by recollection by 81% of the subjects. Overall, the prevalence of persistent pain in those with definite nerve damage 5 to 28 months after surgery was 15%. CONCLUSIONS: Intercostal nerve damage seems to occur in three-quarters of all patients undergoing coronary artery bypass graft-internal thoracic artery surgery. A significant minority may continue to experience bothersome chronic chest wall pain.

Chronic pain in a family of 6 in the context of litigation.

We describe a family of 6 (2 parents and 4 children), evaluated 6 and 8 years after a minor car accident for chronic pain. A near identical complex of multiple physical, constitutional, and psychological symptoms were shared by all family members, all of whom bore the diagnosis of fibromyalgia. The case was brought to court after nearly a decade of symptomatology and extensive use of the health care system. The minor compensation awarded was consumed ultimately by legal fees. Psychosocial/personality issues and iatrogenic and medico-legal contributions in the evolution and resolution of the legal claim are discussed.

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.

Drug interactions in human neuropathic pain pharmacotherapy.

Current practice predicates the use of multiple drug combinations in the treatment of neuropathic pain. These combinations may be required because of multiple pain symptoms directly arising from neuropathic pathology, other symptoms attributable to the chronicity and severity of the patient's pain or conditions unrelated to their pain. A fear exists that combination drug use or the addition of a new drug to a therapeutic regimen may lead to increased drug toxicity or decreased efficacy. Many of the drug interactions of significance to neuropathic pain physicians involve the cytochromes P450 2D6 and 3A3/4 isoenzymes. Drug interactions should be more predictable based on the knowledge of which compounds induce, inhibit or are metabolized by specific cytochrome P450 enzymes. Mechanisms of induction or inhibition of biotransformation via the P450 hepatic enzyme system are discussed and various inducers, inhibitors and substrates relating to neuropathic pain pharmacotherapy are listed.

Hematuria-loin pain syndrome: its existence as a discrete clinicopathological entity cannot be supported.

OBJECTIVE: To (a) review existing literature and current concepts on Hematuria-Loin Pain Syndrome (HLPS) and (b) to describe seven cases of this syndrome. PATIENTS AND SETTING: Seven HLPS patients seen over a period of 8 years by the pain and nephrology services of the Toronto Hospital, Toronto, Ontario, Canada. METHODS AND RESULTS: Retrospective analysis was performed. All patients were remarkable for the variability of clinical presentation, pain characteristics, and dissociation of pain and hematuria occurrence. Routine renal investigations revealed different benign kidney pathologies in 5 of 7 patients. All patients, however, displayed variable combinations of personality factors, drug seeking behaviour, psychopathology, and presence of significant psychosocial stressors. Four cases were managed conservatively with antidepressants, anxiolytics, and supportive counseling and did very well despite persistent hematuria in two. CONCLUSIONS: HLPS does not constitute a distinct clinicopathological entity. In a minority of cases only underlying kidney pathology is related to pain, and in many cases psychosocial stressors and underlying psychopathology may play a significant role in the reported disabling pain. A concerted medical/psychological approach is advocated.

Effect of intravenous sodium amytal on cutaneous limb temperatures and sympathetic skin responses in normal subjects and pain patients with and without Complex Regional Pain Syndromes (type I and II). I.

This study examined the effects of intravenous administration of sodium amytal (SA), a medium action barbiturate, on cutaneous limb temperatures and sympathetic skin responses (SSR) to electrical stimulation. Eight normal volunteers and 13 patients with musculoskeletal pain, somatoform pain disorders or nerve/root injury (with findings strictly limited to the distribution of the distribution of the involved nerve) were compared to 15 patients with Complex Regional Pain syndromes (one of whom had documented nerve injury). The Complex Regional Pain Syndromes (CRPS) patients were characterized by the presence of severe diffuse limb pain and extraterritorial sensory, sudomotor and vasomotor abnormalities (i.e., not confined to the site of injury or the distribution of the injured nerve). The CRPS patients were different from the normal controls and the non-CRPS patients in their tendency to warm significantly many of their limbs (not just the symptomatic ones). SSR were reduced or lost in a few limbs only in all three groups, irrespective of the increase or decrease of limb temperature and the side of symptoms. We argue that the enhanced thermogenic effect of SA in CRPS patients is due to generalized central changes of thermoregulatory control specifically in this group.

Effect of intravenous sodium amytal on cutaneous sensory abnormalities, spontaneous pain and algometric pain pressure thresholds in neuropathic pain patients: a placebo-controlled study. II.

This study investigated the behaviour exhibited by 17 neuropathic pain patients (almost half of whom had documented neurological injury) with diffuse pain and extraterritorial sensory, sudomotor and vasomotor abnormalities, under the influence of intravenous administration of saline-controlled sodium amytal (SA), a medium action barbiturate. After SA (but not after normal saline) infusion, there was a dramatic and selective reduction of allodynia (touch-evoked pain) in all patients displaying this phenomenon, while pin prick and cold hypo- or hyperalgesia, as well as algometric pressure thresholds of the symptomatic limb (as a measurement of deep pain) were minimally changed in most patients. Spontaneous subjective pain was reduced substantially but not totally. The patients were able (once allodynia was eliminated) to recognize a deep-seated pain of which they were unaware before, evoked by firm but gentle palpation of the limb. Sympathetic blocks and A-fibre ischemic blocks in several patients and spinal stimulation in one patient produced effects identical to those observed during SA administration. The deep pain component was maintained despite elimination of allodynia even under stages of sleep induced by SA, at which time the patients would withdraw only the symptomatic limb upon firm but gentle palpation. We argue that neuropathic pain patients have two separate pain components, a cutaneous one (touch-evoked pain or allodynia) mediated by large fibres as a product of central sensitization, and a deep pain component mediated via nociceptors, which can be easily discriminated during systemic administration of SA.

Persistent neuropsychological deficits following whiplash: evidence for chronic mild traumatic brain injury?

OBJECTIVE: To investigate claims of neuropsychological evidence for acquired brain damage (axonal degeneration) in chronic whiplash. DESIGN: Fifteen whiplash patients (Whiplash) were compared with 10 patients who had documented moderate-to-severe head injury (Mod-Sev), and with 24 patients who had chronic pain syndrome (CPS) and no history of head injury on two tests of mental efficiency considered highly sensitive to and specific for the subtle effects of brain trauma. All 3 groups, assessed 4 years after onset in a teaching hospital setting were matched for age, education, and IQ. Exclusion criteria included narcotics/benzo-diazepines or (suspected) malingering. Subjective ratings of depression and pain were collected as well as objective indices of outcome (return to work/school). MEASURES: Neuropsychological test scores were subjected to ANOVA followed by regression analysis regarding the possible effects of age, IQ, pain, and mood ratings. RESULTS: No differences between the Whiplash, Mod-Sev, or CPS groups on the neuropsychological tests emerged. IQ was strongly related to mental efficiency. Counterintuitively, Mod-Sev patients complained of less depression and pain than did Whiplash or CPS patients (where no differences were seen) and displayed a better outcome. Finally, although results from 3 of the original 18 patients in the Whiplash group were later discarded for malingering, no malingering was detected in the 2 other groups. CONCLUSIONS: The theory of neuronal degeneration in the etiology of whiplash-related cognitive complaints was not supported, nor was the specificity of neuropsychological tests in detecting the subtle effects of brain trauma.

Thoracic outlet syndrome after motor vehicle accidents in a Canadian pain clinic population.

OBJECTIVE: To record symptoms and signs, operative findings, and long-term outcome in operated and nonoperated patients with the diagnosis of thoracic outlet syndrome after a motor vehicle accident. DESIGN: Descriptive prospective study. SETTING: Pain clinic population in the Toronto Hospital (Western Division), Toronto, Ontario, Canada. PATIENTS: Thirty-two patients diagnosed as having thoracic outlet syndrome after injuries sustained in a car accident (based on specific symptoms and signs as well as exclusion of other disorders generating brachialgia). INTERVENTIONS: Conservative management versus transaxillary or supraclavicular exploration of the thoracic outlet. OUTCOME MEASURES: Pain/symptom relief. RESULTS: Most patients presented with pain and paresthesiae, but conspicuous discoloration of the symptomatic extremity was seen in 41%. Osseous anomalies were seen in 22% of the patients in simple neck x-rays. Vascular studies were abnormal in 24% of tested patients. During transaxillary first rib resection in 15 patients, 87% were found to have musculotendinous and less often osseous anomalies compromising primarily the lower trunk of the brachial plexus. Long-term follow up demonstrated very good pain relief (based on patients' estimates) only in 47% of the operated patients and 20% of the conservatively treated patients. Reoperation was necessary in six cases through a supraclavicular decompression with only one patient experiencing substantial improvement with long-term follow-up. The difficulties in diagnosis as well as reasons for failures of conservative and surgical management are discussed, and the authors' current protocol for diagnosis and management is presented.

Profile of Caucasian women with possible genetic predisposition to reflex sympathetic dystrophy: a pilot study.

OBJECTIVES: To test possible human lymphocyte antigen (HLA) associations in subjects with reflex sympathetic dystrophy (RSD), and to determine correlation of HLA associations to treatment outcomes. DESIGN: Identification of class I (HLA-A, B, C) and class II (HLA-DR and DQ) (MHC) antigens by well-defined reagents in patients with RSD. SETTING AND PATIENTS: The HLA analysis was performed on 15 Caucasian women attending a university pain clinic and diagnosed with RSD on the basis of strict inclusion and exclusion criteria. OUTCOME MEASURES: Resistance to treatment was defined on the basis of lack of response to conservative management, failure to experience long-term symptom relief after sympathetic blocks, recurrence of pain after sympathectomy, need for palliative treatment, and degree of residual disability at the end of all treatments. RESULTS: A twofold increase of A3, B7, and DR2(15) MHC antigens was observed in the study population compared to control frequencies. Eighty (five of six) of DR2(15)-positive patients proved to be resistant to treatment. CONCLUSIONS: The results of this pilot study are the first to suggest a possible genetic diathesis in RSD patients with poor treatment outcome. If this finding can be confirmed in larger studies, strictly defined RSD could constitute the third neuroimmune disorder (besides multiple sclerosis and narcolepsy) associated with DR2(15). Gene(s) conferring susceptibility to RSD may be present within or near the MHC region of the short arm of chromosome 6. Due to the small size of our study group it is imperative that larger studies be done in RSD patients employing strict diagnostic criteria to confirm or refute our original observations.

Alterations of the three-phase bone scan after sympathectomy.

OBJECTIVE: To evaluate alterations of the three-phase bone scan (TPBS) in patients with the clinical diagnosis of reflex sympathetic dystrophy (RSD) before and after surgical or chemical sympathectomy. DESIGN: The TPBS was done after i.v. administration of 99technetium dimethylphosphonate. Scans were read by one blinded and one nonblinded reviewer (as to site of symptoms and procedure), using a visual grading system devised in our institution. Since there were no statistically significant differences between the two examiners' scores for blood flow, pool, and delayed phases, all scores were averaged and used for comparison before and after sympathectomy. SUBJECTS: Ten women and four men with RSD were observed with 17 TPBSs before and 30 TPBSs after surgical (n = 6) or chemical (n = 8) sympathectomy. RESULTS: All three phases of TPBS were significantly enhanced after sympathectomy in 11 of 14 patients in a pattern indistinguishable from that very commonly reported in florid RSD. The increased uptake occurred within 24 h after the procedure, normalized as early as 3 months in some scans, and remained abnormal in some patients in the 12-month follow-up period. In total, only 33% of all sympathectomies performed led to long-term symptom relief. CONCLUSIONS: The data demonstrated that alterations in TPBS after sympathectomy are identical to those reported in early RSD and these alterations bear no relationship to the success of sympathectomy regarding pain relief. The mechanisms underlying alterations of TPBS as well as the potential mechanisms of sympathectomy failures are discussed.

Effect of surgical sympathectomy on arterial blood flow in reflex sympathetic dystrophy: Doppler US assessment.

PURPOSE: To assess duplex Doppler ultrasound (US) in providing objective, reproducible measurements of blood flow in patients with reflex sympathetic dystrophy (RSD) who underwent surgical sympathectomy. MATERIALS AND METHODS: Findings in eight adult patients with RSD who were evaluated with arterial duplex Doppler US after surgical sympathetectomy were retrospectively reviewed. Pulsatility index (PI) and waveform characteristics were compared to clinical findings (temperature and sudomotor state) in sympathectomized limbs. RESULTS: Warm and dry limbs yielded a consistently low PI (usually less than 2) and biphasic waveform. Cold and clammy limbs, which indicated failed sympathectomy, produced a high PI (usually greater than 4) and triphasic waveform. The Doppler waveform promptly reverted with the return of sympathetic tone in patients who had clinical relapse. CONCLUSION: Duplex Doppler US may be useful for objective follow-up of RSD patients after sympathectomy.