The neuropathic component in persistent postsurgical pain: A systematic literature review

Persistent postsurgical pain (PPSP) is a frequent and often disabling complication of many surgical procedures. Nerve injury–induced neuropathic pain (NeuP) has repeatedly been proposed as a major cause of PPSP. However, there is a lack of uniformity in NeuP assessment across studies, and the prevalence of NeuP may differ after various surgeries. We performed a systematic search of the PubMed, CENTRAL, and Embase databases and assessed 281 studies that investigated PPSP after 11 types of surgery. The prevalence of PPSP in each surgical group was examined. The prevalence of NeuP was determined by applying the recently published NeuP probability grading system. The prevalence of probable or definite NeuP was high in patients with persistent pain after thoracic and breast surgeries—66% and 68%, respectively. In patients with PPSP after groin hernia repair, the prevalence of NeuP was 31%, and after total hip or knee arthroplasty it was 6%. The results suggest that the prevalence of NeuP among PPSP cases differs in various types of surgery, probably depending on the likelihood of surgical iatrogenic nerve injury. Because of large methodological variability across studies, a more uniform approach is desirable in future studies for evaluating persistent postsurgical NeuP.     

Exuberant sprouting of sensory and sympathetic nerve fibers in nonhealed bone fractures and the generation and maintenance of chronic skeletal pain

Skeletal injury is a leading cause of chronic pain and long-term disability worldwide. While most acute skeletal pain can be effectively managed with nonsteroidal anti-inflammatory drugs and opiates, chronic skeletal pain is more difficult to control using these same therapy regimens. One possibility as to why chronic skeletal pain is more difficult to manage over time is that there may be nerve sprouting in nonhealed areas of the skeleton that normally receive little (mineralized bone) to no (articular cartilage) innervation. If such ectopic sprouting did occur, it could result in normally nonnoxious loading of the skeleton being perceived as noxious and/or the generation of a neuropathic pain state. To explore this possibility, a mouse model of skeletal pain was generated by inducing a closed fracture of the femur. Examined animals had comminuted fractures and did not fully heal even at 90+ days post fracture. In all mice with nonhealed fractures, exuberant sensory and sympathetic nerve sprouting, an increase in the density of nerve fibers, and the formation of neuroma-like structures near the fracture site were observed. Additionally, all of these animals exhibited significant pain behaviors upon palpation of the nonhealed fracture site. In contrast, sprouting of sensory and sympathetic nerve fibers or significant palpation-induced pain behaviors was never observed in naïve animals. Understanding what drives this ectopic nerve sprouting and the role it plays in skeletal pain may allow a better understanding and treatment of this currently difficult-to-control pain state.     

Characterization of persistent postoperative pain by quantitative sensory testing

Postoperative pain remains inadequately treated, and it has been estimated that 5–10% undergoing surgery will develop moderate to severe persistent pain leading to chronic physical disability and psychosocial distress.Quantitative sensory testing (QST) is a graded, standardized activation of the sensory system either by mechanical, thermal or electrical stimuli, with assessment of the evoked psychophysical response. QST has been used in prospective assessments of how and why some individuals develop persistent postoperative pain.This comprehensive review describes, first, QST as a predictive research tool in studies investigating the correlation between responses to preoperatively applied experimental pain stimuli and clinical postoperative pain. Second, the use of QST as a valuable prognostic, sequential assessment tool in surgical procedure specific research is presented. Third, the implications of these findings for use of QST in future research are discussed. More rational design of predictive studies in PPP, based on surgical procedure specific approaches, is needed in order to improve our understanding of prevention and management of this debilitating postsurgical condition.     

Self-reported somatosensory symptoms of neuropathic pain in fibromyalgia and chronic widespread pain correlate with tender point count and pressure-pain thresholds

Widespread pain and pain hypersensitivity are the hallmark of fibromyalgia, a complex pain condition linked to central sensitization. In this study the painDETECT questionnaire (PDQ), validated to identify neuropathic pain and based on pain quality items, was applied in a cross-sectional sample of patients with chronic widespread pain (CWP). The aims of the study were to assess the patient-reported sensory neuropathic symptoms by PDQ and to correlate these with tender point (TP) count and pressure-pain thresholds. Eighty-one patients (75 F, 6 M) with CWP (ACR-criteria) filled in the PDQ. Manual TP examination was conducted according to ACR guidelines. Computerized cuff pressure algometry was used for the assessment of pressure-pain detection thresholds (PDT, unit: kPa) and pressure-pain tolerance thresholds (PTT, unit: kPa). Mean TP count was 14.32 (range: 2-18), mean PDQ score 22.75 (range: 5-37). Mean PDT was 8.8 kPa (range: 2-36) and mean PTT 30.9 kPa (range: 4-85). Deep-tissue hyperalgesia was the predominant somatosensory symptom reported in 83%, but other neuropathic symptoms were also frequent, e.g. burning 51% and prickling 47%. Statistically significant correlations were found between PDQ score and TP count: r = 0.35 (p < 0.01), and PDQ score and PDT: r = 0.45 (p < 0.01), and PTT: r = 0.43 (p < 0.01). The study indicates that pain in CWP has neuropathic features, and that the presence and number of tender points are associated with neuropathic pain symptoms. A high mean PDQ score was found to correlate with TP count and pressure-pain thresholds. The PDQ may become a useful tool assisting in the identification of central sensitization in patients with CWP and in the future diagnostic assessment fibromyalgia.     

Association of self-reported painful symptoms with clinical and neurophysiologic signs in HIV-associated sensory neuropathy

Sensory neuropathy (HIV-SN) is a common cause of pain in HIV-infected people. Establishing a diagnosis of HIV-SN is important, especially when contemplating opioid use in high-risk populations. However physical findings of HIV-SN may be subtle, and sensitive diagnostic tools require specialized expertise. We investigated the association between self-report of distal neuropathic pain and/or paresthesias (DNPP) and objective signs of HIV-SN. Data were obtained from the Central Nervous System HIV Antiretroviral Therapy Effects Research (CHARTER) study. Out of 237 participants, 101 (43%) reported DNPP. Signs of HIV-SN were measured by a modified Total Neuropathy Score (TNS), composed of six objective sensory subscores (pin sensibility, vibration sensibility, deep tendon reflexes, quantitative sensory testing for cooling and vibration, and sural sensory amplitude). Self-report of DNPP was associated with all six TNS items in univariate analysis and with four TNS items in multivariate analysis. The sensitivity and specificity of self-report of DNPP in detecting the presence of a sensory abnormality were 52% and 92%, respectively with a PPV of 96% and a NPV of 34%. Increasing intensity of pain measured on a visual analog scale was associated with increasing severity of sensory abnormality. In summary, our results suggest that HIV-infected patients reporting symptoms consistent with HIV-SN, such as tingling, pins and needles, or aching or stabbing pain in the distal lower extremities, usually have objective evidence of HIV-SN on neurologic examination or with neurophysiologic testing. This finding holds true regardless of demographic factors, depression or substance use history.     

Identification of patient subgroups and risk factors for persistent arm/shoulder pain following breast cancer surgery

PurposeIn this prospective, longitudinal study, we extend our findings on persistent breast pain in patients (n = 398) following breast cancer surgery and evaluate the prevalence and characteristics of persistent pain in the arm/shoulder. In addition, differences in the severity of common symptoms and quality of life outcomes measured prior to surgery, among the arm pain classes, were evaluated.Methods and samplePatients were recruited from Breast Care Centers located in a Comprehensive Cancer Center, two public hospitals, and four community practices. Patients were assessed prior to and monthly for six months following breast cancer surgery.ResultsUsing growth mixture modeling, patients were classified into no (41.6%), mild (23.6%), and moderate (34.8%) arm pain classes based on ratings of worst arm/shoulder pain. Compared to the no pain class, patients in the moderate pain class were significantly younger, had a higher body mass index, and were more likely to report preoperative breast pain and swelling in the affected breast. In addition, patients in the moderate pain class reported higher levels of depression, anxiety, and sleep disturbance than the no pain class.ConclusionsFindings suggest that approximately 35% of women experience persistent levels of moderate arm/shoulder pain in the first six months following breast cancer surgery. Moderate arm/shoulder pain is associated with clinically meaningful decrements in functional status and quality of life.     

Prevalence of chronic pain with neuropathic characteristics in the general population

We conducted a large nationwide postal survey to estimate the prevalence of chronic pain with or without neuropathic characteristics in the French general population. A questionnaire aimed at identifying chronic pain (defined as daily pain for at least 3 months), evaluating its intensity, duration and body locations, was sent to a representative sample of 30,155 subjects. The DN4 questionnaire was used to identify neuropathic characteristics. Of the questionnaires, 24,497 (81.2%) were returned and 23,712 (96.8%) could be assessed. Seven thousand five hundred and twenty-two respondents reported chronic pain (prevalence=31.7%; [95%CI: 31.1-32.3]) and 4709 said the pain intensity was moderate to severe (prevalence=19.9%; [95%CI: 19.5-20.4]). Neuropathic characteristics were reported by 1631 respondents with chronic pain (prevalence=6.9%; [95%CI: 6.6-7.2]), which was moderate to severe in 1209 (prevalence=5.1% [95%CI: 4.8-5.4]). A higher prevalence of chronic pain with neuropathic characteristics was associated with middle age (50-64 years), manual professions and those living in rural areas. It was more frequently located in the lower limbs and its intensity and duration were higher in comparison with chronic pain without neuropathic characteristics. This large national population-based study indicates that a significant proportion of chronic pain patients report neuropathic characteristics. We identified distinctive socio-demographic profile and clinical features indicating that chronic pain with neuropathic characteristics is a specific health problem.     

Chronic pain following donor nephrectomy – A study of the incidence,nature and impact of chronic post‐nephrectomy pain

Chronic pain is a consequence of some types of surgery, but its incidence following open donor nephrectomy has never been investigated. We surveyed 123 patients who underwent open donor nephrectomy at our institution over a 10‐year period, to determine the incidence, severity and nature of chronic pain and its effect on quality of life. Of the 81 (66%) responders, 27 (33%) had experienced prolonged pain, and 21 (26%) still had chronic pain related to their surgery. The overall incidence of severe, disabling pain (visual analogue score ≥7) was 12% and of neuropathic pain was 14%. The average loss in quality adjusted life years (QALYs) was 1.053 for chronic pain sufferers, but was 1.851 for those who suffered specifically from neuropathic pain. Only one third of patients with chronic pain were receiving any treatment, and none were receiving neuropathic adjuvants or specialist pain management interventions. We conclude that the incidence of chronic pain following donor nephrectomy is underestimated and therefore under managed. Given the voluntary and altruistic nature of this procedure, and the enormous personal and social benefits which result from successful donor transplantation, those involved with the preparation and post‐operative management should be more aware of, and actively question donors about chronic pain so that diagnosis and appropriate therapy can be commenced as early as possible.     

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.     

聚丙烯酰胺水凝胶隆乳术后取出路径及影响再次隆乳原因探讨

目的探讨聚丙烯酰胺水凝胶(PAHG)隆乳术后取出路径及影响再次隆乳原因。方法在彩超、CT的指导下,对52例PAHG隆乳术的患者分别采用经腋窝、乳晕、乳房皱襞下等切口清除,同时对23例患者同期作了硅凝胶假体隆乳,11例患者在半年后作了硅凝胶假体隆乳。结果 47例患者术后自觉症状消失,彩超、CT检查乳腺、胸大肌及其间隙未发现PAHG,34例同期或延期隆乳的患者乳房形态满意,未出现术前的症状及心理问题。结论术前经彩超、CT检查了解PAHG的分布情况,根据分布情况采取适当的取出路径,胸大肌及其后间隙是否完整影响再次隆乳。     

Persistent Postmastectomy Pain in Breast Cancer Survivors: Analysis of Clinical,Demographic, and Psychosocial Factors

Persistent postmastectomy pain (PPMP) is increasingly recognized as a major individual and public health problem. Although previous studies have investigated surgical, medical, and demographic risk factors, in this study we aimed to more clearly elucidate the relationship of psychosocial factors to PPMP. Postmastectomy patients (611) were queried about pain location, severity, and burden 38.3 ± 35.4 months postoperatively. Validated questionnaires for depressive symptoms, anxiety, sleep, perceived stress, emotional stability, somatization, and catastrophizing were administered. Detailed surgical, medical, and treatment information was abstracted from patients' medical records. One third (32.5%) of patients reported PPMP, defined as ≥3/10 pain severity in the breast, axilla, side, or arm, which did not vary according to time since surgery. Multiple regression analysis revealed significant and independent associations between PPMP and psychosocial factors, including catastrophizing, somatization, anxiety, and sleep disturbance. Conversely, treatment-related factors including surgical type, axillary node dissection, surgical complication, recurrence, tumor size, radiation, and chemotherapy were not significantly associated with PPMP. These data confirm previous studies suggesting that PPMP is relatively common and provide new evidence of significant associations between psychosocial characteristics such as catastrophizing with PPMP, regardless of the surgical and medical treatment that patients receive, which may lead to novel strategies in PPMP prevention and treatment.     

Hemiplegic shoulder pain: Evidence of a neuropathic origin

Hemiplegic shoulder pain (HSP) is common after stroke. Whereas most studies have concentrated on the possible musculoskeletal factors underlying HSP, neuropathic aspects have hardly been studied. Our aim was to explore the possible neuropathic components in HSP, and if identified, whether they are specific to the shoulder or characteristic of the entire affected side. Participants included 30 poststroke patients, 16 with and 14 without HSP, and 15 healthy controls. The thresholds of warmth, cold, heat-pain, touch, and graphesthesia were measured in the intact and affected shoulder and in the affected lower leg. They were also assessed for the presence of allodynia and hyperpathia, and computed tomography/magnetic resonance imaging scans of the brain were reviewed. In addition, chronic pain was characterized. Participants with HSP exhibited higher rates of parietal lobe damage (P < 0.05) compared to those without HSP. Both poststroke groups exhibited higher sensory thresholds than healthy controls. Those with HSP had higher heat-pain thresholds in both the affected shoulder (P < 0.001) and leg (P < 0.01), exhibited higher rates of hyperpathia in both these regions (each P < 0.001), and more often reported chronic pain throughout the affected side (P < 0.001) than those without HSP. The more prominent sensory alterations in the shoulder region suggest that neuropathic factors play a role in HSP. The clinical evidence of damage to the spinothalamic-thalamocortical system in the affected shoulder and leg, the presence of chronic pain throughout the affected side, and the more frequent involvement of the parietal cortex all suggest that the neuropathic component is of central origin.     

隆乳术后病人乳房按摩健康教育需求及相关情况的调查分析

[目的]了解隆乳术后病人乳房按摩健康教育的需求情况。[方法]采用自制问卷对65例隆乳术后病人进行乳房按摩相关健康教育需求的调查。[结果]隆乳术后病人乳房按摩健康教育总体需求较高,认为最需要或需要的占95.16%,隆乳术后病人对健康教育方式和内容有明显偏好,隆乳术后病人对隆乳术及乳房按摩相关知识需求强烈。[结论]对隆乳术后病人进行乳房按摩健康教育很有必要,乳房按摩技术、相关并发症产生的原因及预防措施应该成为今后健康教育的重点内容。     

SEPS镜辅助下的乳房整形术:隆乳和注射隆乳异物清除

目的直视下探查分离假体置入腔隙及聚丙烯酰胺水凝胶注射隆乳术后形成的多发性异物囊腔结节,减轻组织创伤,提高隆乳术效果和异物清除率。方法自2001年3月起在SEPS镜辅助下完成21例乳房整形术,其中13例为隆乳术,8例为聚丙烯酰胺水凝胶注射隆乳术后坚决要求行异物清除术,术前B超对异物定位标记,全部手术经腋部切口,在SEPS镜辅助下对皮下、乳腺内、腺体后、胸肌内等不同解剖层次的异物结节囊腔逐一探查剥离,清除异物,隆乳术者于胸大肌下剥离假体置入腔隙。结果术后无血肿、感染,伤口Ⅰ期愈合。随访6￣18个月,注射隆乳所致乳房疼痛、乳腺结节和双侧乳房不对称畸形等术前不良临床表现消失,术后复查乳腺B超已无异物包块征象;隆乳术后假体无移位,乳房外形及手感良好。结论SEPS镜辅助直视下行注射隆乳异物取出和隆乳较常规盲视下操作组织创伤小,更安全,确切,可靠,不失为注射隆乳异物清除和隆乳的良好方法。     

隆乳术后病人乳房按摩健康教育需求及相关情况的调查分析

[目的]了解隆乳术后病人乳房按摩健康教育的需求情况.[方法]采用自制问卷对65例隆乳术后病人进行乳房按摩相关健康教育需求的调查.[结果]隆乳术后病人乳房按摩健康教育总体需求较高,认为最需要或需要的占95.16%,隆乳术后病人对健康教育方式和内容有明显偏好,隆乳术后病人对隆乳术及乳房按摩相关知识需求强烈.[结论]对隆乳术后病人进行乳房按摩健康教育很有必要,乳房按摩技术、相关并发症产生的原因及预防措施应该成为今后健康教育的重点内容.     

Depression,anxiety, health-related quality of life and pain in patients with chronic fibromyalgia and neuropathic pain

Chronic pain is often associated with comorbidities such as anxiety and depression, resulting in a low health-related quality of life. The mechanisms underlying this association are not clear, but a disturbance in the pain control systems from the brain stem has been suggested. Thirty neuropathic pain (NP) patients, 28 patients with fibromyalgia (FM), and 26 pain-free age- and gender-matched controls were included and examined with respect to mental distress (self-rated Symptom Checklist-92), depression (doctor-rated Hamilton Depression Scale and self-rated Major Depression Inventory), and anxiety (doctor-rated Hamilton Anxiety Scale and self-rated Anxiety Inventory). In addition, patients assessed their health-related quality of life (SF-36). Chronic pain patients with FM and NP had significantly more mental distress including depression and anxiety than healthy controls both by self-rating and by a professional rating. However, these scores are low compared to other studies on mental distress in chronic pain patients. Only few chronic pain patients meet the diagnostic criteria for depression (NP 3.3%, FM 7.1%), and associations between pain and mental symptoms were only found in the FM group despite similar pain intensities. The findings suggest that different mechanisms are responsible for the development of mood disorders in the two patient groups.     

Referred sensations and neuropathic pain following spinal cord injury

It has been proposed that painful and non-painful referred sensations (RSs) are associated with reorganization of sensory pathways in patients with complete spinal cord injury (SCI). In order to investigate the referred sensation (RS) phenomenon and its correlation with neuropathic pain (NP) 48 patients with complete SCI, 24 with chronic NP and 24 without pain or paraesthesias were studied using clinical examination and neurophysiological tests. Patients reporting RSs were re-examined at 2 and 10 weeks after the first examination. We defined the presence of RS as sensations perceived below the injury level in response to touch and pinprick stimuli in various body points above the injury level. The examination was carried out by one researcher applying the stimuli to the patient under two visual conditions (open and closed eyes), and then asking the patient to make tactile self-stimulation. Seven patients with SCI and NP (29%) reported RS below the injury level. RS were well located and consistently evoked at repeated examinations. Touch and pinprick stimulation elicited similar RS that were non-painful in six patients and painful in one. Visual feedback did not change RS perception and characteristics. None of the patients in the SCI group without NP presented RS. In conclusion, our results indicate that RS is relatively frequent in patients with complete SCI and NP. The common occurrence of RS in patients with NP and the location of the sensations in the same area as NP suggest that pain and RS share common pathophysiological mechanisms.