Nefopam analgesia and its role in multimodal analgesia: A review of preclinical and clinical studies.

Nefopam is a non-opioid, non-steroidal, centrally acting analgesic drug used to prevent postoperative pain, primarily in the context of multimodal analgesia. This paper reviews preclinical and clinical studies in which nefopam has been combined with opioids, non-steroidal anti-inflammatory compounds, and paracetamol. This report focuses on the literature during the last decade and discusses the translational efforts between animal and clinical studies in the context of multimodal or balanced analgesia. In preclinical rodent models of acute and inflammatory pain, nefopam combinations including opioids revealed a synergistic interaction or enhanced morphine analgesia in six out of seven studies. Nefopam combinations including non-steroidal anti-inflammatory drugs (NSAIDs) (aspirin, ketoprofen or nimesulide) or paracetamol likewise showed enhanced analgesic effects for the associated compound in all instances. Clinical studies have been performed in various types of surgeries involving different pain intensities. Nefopam combinations including opioids resulted in a reduction in morphine consumption in 8 out of 10 studies of severe or moderate pain. Nefopam combinations including NSAIDs (ketoprofen or tenoxicam) or paracetamol also demonstrated a synergic interaction or an enhancement of the analgesic effect of the associated compound. In conclusion, this review of nefopam combinations including various analgesic drugs (opioids, NSAIDs and paracetamol) reveals that enhanced analgesia was demonstrated in most preclinical and clinical studies, suggesting a role for nefopam in multimodal analgesia based on its distinct characteristics as an analgesic. Further clinical studies are needed to evaluate the analgesic effects of nefopam combinations including NSAIDs or paracetamol.

Nefopam and meperidine are infra-additive on the shivering threshold in humans.

BACKGROUND: Induction of therapeutic hypothermia is often complicated by shivering. Nefopam, a nonsedative benzoxazocine analgesic, reduces the shivering threshold (triggering core temperature) with minimal side effects. Consequently, nefopam is an attractive drug for inducing therapeutic hypothermia. However, nefopam alone is insufficient and thus needs to be combined with another drug. Meperidine also reduces the shivering threshold. We therefore determined whether the combination of nefopam and meperidine is additive, infra-additive, or synergistic on the shivering threshold. METHODS: Ten volunteers were each studied on 4 randomly assigned days. In random order, they were given the following treatments: (1) control, no drug; (2) nefopam to a target concentration of 0.1 µg/mL; (3) meperidine to a target concentration of 0.1 µg/mL; and (4) both nefopam and meperidine at target concentrations of 0.1 µg/mL each. Lactated Ringer's solution at 4°C was infused to decrease core temperature while mean skin temperature was kept near 30.5°C. The core temperature that increased oxygen consumption >25% defined the shivering threshold. RESULTS: Nefopam reduced the shivering thresholds by 0.7°C ± 0.3°C compared with no drug. Meperidine reduced the shivering thresholds by 0.4°C ± 0.3°C compared with no drug. When combined, the shivering threshold decreased by only 0.6°C ± 0.4°C, which was about half what would have been expected based on the individual effects of each drug (P < 0.001). The effect of combined nefopam and meperidine on the shivering threshold was thus infra-additive. CONCLUSIONS: The combination of nefopam and meperidine should be avoided for induction of therapeutic hypothermia. Better options would be combinations of drugs that are at least additive or even synergistic.

Nefopam and alfentanil additively reduce the shivering threshold in humans whereas nefopam and clonidine do not.

BACKGROUND: Induction of therapeutic hypothermia is often complicated by shivering. Nefopam reduces the shivering threshold with minimal side effects. Consequently, nefopam is an attractive component for induction of therapeutic hypothermia. However, nefopam alone is insufficient; it will thus need to be combined with another drug. Clonidine and alfentanil each reduce the shivering threshold. This study, therefore, tested the hypothesis that nefopam, combined either with clonidine or alfentanil, synergistically reduces the shivering threshold. METHODS: For each combination, ten volunteers were studied on 4 days. Combination 1: (1) control (no drug); (2) nefopam (100 ng/ml); (3) clonidine (2.5 microg/kg); and (4) nefopam plus clonidine (100 ng/ml and 2.5 microg/kg, respectively). Combination 2: (1) control (no drug); (2) nefopam (100 ng/ml); (3) alfentanil (150 ng/ml); and (4) nefopam plus alfentanil (100 ng/ml and 150 ng/ml, respectively). Lactated Ringer's solution (approximately 4 degrees C) was infused to decrease core temperature. Mean skin temperature was maintained at 31 degrees C. The core temperature that increased oxygen consumption to more than 25% of baseline identified the shivering threshold. RESULTS: With nefopam and clonidine, the shivering thresholds were significantly lower than on the control day. The shivering threshold decreased significantly less than would be expected on the basis of the individual effects of each drug (P = 0.034). In contrast, the interaction between nefopam and alfentanil on shivering was additive, meaning that the combination reduced the shivering threshold as much as would be expected by the individual effect of each drug. CONCLUSIONS: Nefopam and alfentanil additively reduce the shivering threshold, but nefopam and clonidine do not.

Lack of impact of intravenous lidocaine on analgesia, functional recovery, and nociceptive pain threshold after total hip arthroplasty.

BACKGROUND: The analgesic effect of perioperative low doses of intravenous lidocaine has been demonstrated after abdominal surgery. This study aimed to evaluate whether a continuous intravenous low-dose lidocaine infusion reduced postoperative pain and modified nociceptive pain threshold after total hip arthroplasty. METHODS: Sixty patients participated in this randomized double-blinded study. Patients received lidocaine 1% (lidocaine group) with a 1.5 mg/kg intravenous bolus in 10 min followed by a 1.5 mg . kg . h intravenous infusion or saline (control group). These regimens were started 30 min before surgical incision and stopped 1h after skin closure. Lidocaine blood concentrations were measured at the end of administration. In both groups, postoperative analgesia was provided exclusively by patient-controlled intravenous morphine. Pain scores, morphine consumption, and operative hip flexion were recorded over 48 h. In addition, pressure pain thresholds and the extent of hyperalgesia around surgical incision were systematically measured at 24 and 48 h. RESULTS: In comparison with the placebo, lidocaine did not induce any opioid-sparing effect during the first 24 h (median [25-75% interquartile range]; 17 mg [9-28] vs. 15 mg [8-23]; P = 0.54). There was no significant difference regarding the effects of lidocaine and placebo on pain score, pressure pain thresholds, extent in the area of hyperalgesia, and maximal degree of active hip flexion tolerated. Mean plasma lidocaine concentration was 2.1 +/- 0.4 mug/ml. CONCLUSION: Low dose perioperative intravenous lidocaine after total hip arthroplasty offers no beneficial effect on postoperative analgesia and does not modify pressure and tactile pain thresholds.

Antiinflammatory effect of peripheral nerve blocks after knee surgery: clinical and biologic evaluation.

BACKGROUND: Nerve blocks provide analgesia after surgery. The authors tested whether nerve blocks have antiinflammatory effects. METHODS: Patients had combined sciatic (single-shot) and continuous femoral block (48 h) (block group) or morphine patient-controlled analgesia after total knee arthroplasty. Pain at rest and upon movement was monitored at 1 (D1), 4 (D4), and 7 days (D7) and 1 (M1) and 3 months (M3) after surgery. Knee inflammation was evaluated (skin temperature, knee circumference) before surgery and at D1, D4, D7, M1, and M3. Plasma cytokine concentrations (interleukin [IL]-6, IL-1beta, tumor necrosis factor [TNF], IL-10, soluble receptor 1 of TNF [sTNF-R1]) were measured before surgery and at 4 h, D1, D4, and D7 after surgery. Capsule and synovial membrane cytokines were measured (IL-6, TNF, IL-1, IL-10). Knee flexion was evaluated before surgery and at D1, D4, D7, M1, and M3. Morphine use and recovery time to autonomy were monitored. RESULTS: Pain at rest and upon movement was lower in the block group than in patient-controlled analgesia patients between D1 and D7 (analysis of variance, P < 0.005). Knee flexion was improved in the block group for D1 to M1 (analysis of variance, P < 0.0001). Block group patients recovered nonassisted mobilization (t test, P = 0.04) and toilet use (t test, P = 0.03) more rapidly. Knee circumference and skin temperature were lower in the block group between D1 and D7 (analysis of variance, P < 0.05). Synovial membrane IL-1 (P < 0.05) and IL-10 (P < 0.01) increased, and plasma IL-6 and sTNF-R1 peaked at 24 h, with no difference between groups. CONCLUSION: Nerve blocks inhibited clinical inflammation after total knee arthroplasty, with no change in tissue and plasma cytokine concentrations.

The evolution of primary hyperalgesia in orthopedic surgery: quantitative sensory testing and clinical evaluation before and after total knee arthroplasty.

BACKGROUND: Quantitative sensory testing (QST) allows precise characterization of sensory deficits and painful symptoms and may offer additional information on the pathophysiology of postoperative pain. METHODS: We evaluated 20 patients scheduled for total knee arthroplasty clinically and with QST before surgery, at 1 and 4 days after surgery, and at 1 and 4 mo after surgery. The clinical evaluation included preoperative pain and inflammation of the operative knee, postoperative assessment of pain at rest and during movement (Visual Analog Scale score), cumulative morphine consumption, and circumference and temperature of both knees. QST included thermal and mechanical (pressure) pain threshold measurements and assessment of responses to suprathreshold stimuli. Brush-evoked allodynia was also evaluated. Measurements were taken on the operative knee, contralateral knee, and on the hand as a control site. RESULTS: All patients had prolonged and severe pain before surgery and inflammation of the operative knee. Preoperative QST provided evidence of heat hyperalgesia in the inflammatory area on the operative knee, but absence of punctate or brush-evoked allodynia in the adjacent noninflamed area. Patients had intense postoperative pain, mostly induced by movement. Primary heat hyperalgesia was present on the operative knee on the first and fourth day after surgery, and was associated with punctate mechanical allodynia in the inflammatory area, but not in the adjacent noninflamed area. Postoperative morphine consumption was correlated with preoperative heat hyperalgesia (r = 0.63; P = 0.01). QST returned to baseline at the 4-mo evaluation. Only four patients had moderate knee pain induced by movement at that time. CONCLUSION: Heat hyperalgesia was the predominant QST symptom associated with perioperative pain after total knee arthroplasty, and was predictive of postoperative morphine consumption.

The influence of timing of administration on the analgesic efficacy of parecoxib in orthopedic surgery.

BACKGROUND: Parecoxib, a selective cyclooxygenase-2 inhibitor, may reduce postoperative pain without increasing bleeding when administered before surgery. METHODS: We randomly assigned 62 patients scheduled for total hip arthroplasty to the following IV dosing schedule: 1) placebo at induction, at wound closure, and 12 h after induction (control); 2) parecoxib 40 mg at induction, placebo at wound closure, and parecoxib 40 mg 12 h after induction (pre); or, 3) placebo at induction, parecoxib 40 mg at wound closure, and parecoxib 40 mg 12 h after induction (post). Pain scores at rest and with movement were recorded every 4 h for 24 h using a visual analog scale. Treatment side effects were recorded every 4 h. Red cell loss for 5 days after surgery was calculated. RESULTS: Postoperative pain scores were less in the pre and post groups than in the control group. Postoperative bleeding was similar in the three groups. There were no significant differences between the pre and post groups, nor was their any trend suggesting a preemptive analgesic efficacy from preincision administration of parecoxib. Morphine use in the Postanesthesia Care Unit was reduced in the pre and post groups compared with the control group (14.2 +/- 2.0, and 15.7 +/- 2.0, vs 20.4 +/- 2.3 mg), although the trend was only significant (P < 0.05) in the pre group. The first pain score was also reduced in the pre and post groups compared to the control group (56.1 +/- 7.5 and 64.2 +/- 7.0 vs 78.3 +/- 5), but this was also only significant for the pre group (P = 0.001). The delay for first analgesic demand was increased for both the pre and post group compared to the control group (38 +/- 9 and 28.2 +/- 6.6 vs 18 +/- 6 min) but, again, this was only significant for the pre group (P = 0.05). Twenty-four hour consumption of morphine was similar in the pre (26 +/- 12 mg) and post groups (25 +/- 13 mg); both were significantly less than in the control group (47 +/- 27 mg, P < 0.001). CONCLUSIONS: Administration of parecoxib before hip arthroplasty did not provide preemptive analgesia. There was a trend towards improved analgesia immediately after surgery with preincision administration, consistent with the expected time course of nonsteroidal antiinflammatory drug's effect. Perioperative parecoxib administration, consisting of two injections spaced 12 h apart, improved postoperative analgesia over the first 24 h without increasing bleeding.

Evaluation of the ventilator-user interface of 2 new advanced compact transport ventilators.

BACKGROUND: Mechanical ventilation during patient transport frequently utilizes compact portable pneumatic ventilators that have limited ventilator-settings options. New advanced transport ventilators should yield quality improvements, but their user-friendliness needs to be tested. OBJECTIVE: To evaluate the ventilator-user interface of 2 new transport ventilators. METHODS: This was a 2-center descriptive study in which the ventilator-user interfaces of the Oxylog 3000 and Elisée 250 were compared by 20 French senior emergency physicians who were initially unfamiliar with these ventilators. Each physician carried out 15 tasks with each ventilator and then assigned each ventilator a satisfaction score. RESULTS: With the Elisée 250 the task success rate was significantly higher (85.6% vs 66.6% with the Oxylog 3000, p < 0.0001), and the total number of errors was lower (46 vs 113). The main errors were related to inspiratory flow settings with the Oxylog 3000 (31 errors), inspiratory-expiratory ratio settings with the Elisée 250 (11 errors), ventilation mode choice with the Oxylog 3000 (17 errors), trigger sensitivity setting with the Elisée 250 (16 errors) and the Oxylog 3000 (11 errors), and alarm range setting with the Oxylog 3000 (10 errors). The mean satisfaction score was significantly better with the Elisée 250 (81% +/- 7, range 64-92%) than with the Oxylog 3000 (66% +/- 10, range 49-87%) (p < 0.0001). CONCLUSIONS: The Elisée 250 ventilator-user interface was easier to use than that of the Oxylog 3000. The applicability of these results to other types of users will require further studies, but the types of errors found in our study might help future users.

A single preoperative dose of gabapentin (800 milligrams) does not augment postoperative analgesia in patients given interscalene brachial plexus blocks for arthroscopic shoulder surgery.

BACKGROUND: Inadequate analgesia is common after shoulder arthroscopy. Both interscalene blocks and gabapentin are effective methods of pain management under various circumstances. We tested the hypothesis that gabapentin augments postoperative analgesia provided by interscalene brachial plexus block in patients having ambulatory arthroscopic shoulder surgery. METHODS: Sixty patients were randomly assigned to receive oral gabapentin, 800 mg, or placebo 2 h before surgery. An interscalene brachial plexus block with 0.3 mL/kg of 0.5% ropivacaine was performed. General anesthesia was maintained with sevoflurane and included a single 1-microg/kg dose of remifentanil. Postoperative analgesia was initially provided with morphine and subsequently with ketoprofene (150 mg orally twice daily) and a combination of 400 mg acetaminophen and 30 mg dextropropoxyphene as needed. Pain scores, analgesic requirements, and side effects were assessed in the ambulatory unit and at home for 48 h. RESULTS: Emergence from general anesthesia was similar in both groups. There were no significant differences in pain scores, first postoperative request for analgesia, or oral analgesic consumption. The incidence of side effects was comparable in both groups, except that headaches were less frequent in the gabapentin group. CONCLUSION: A single preoperative dose of gabapentin (800 mg) does not augment postoperative analgesia in patients given interscalene brachial plexus blocks for arthroscopic shoulder surgery.

Cardiac function during intraperitoneal CO2 insufflation for aortic surgery: a transesophageal echocardiographic study.

The effect of laparoscopy on cardiac function is controversial. We hypothesized that cardiac dysfunction related to increased afterload could be predominant in patients undergoing elective abdominal aortic repair. To test this hypothesis, we conducted a transesophageal echocardiographic study in 15 patients during laparoscopic aortic surgery. We systematically assessed left ventricular (LV) and right ventricular (RV) functions. Measurements were obtained in the supine position without pneumoperitoneum and with an intraabdominal pressure of 14 mm Hg. Then, patients were turned to the right lateral position without pneumoperitoneum and intraabdominal pressure was increased to 7 mm Hg and to 14 mm Hg. Pneumoperitoneum induced a 25% arterial blood pressure increase and a 38% increase in LV systolic wall stress. A 25% decrease in LV ejection fraction and an 18% decrease in LV stroke volume were observed, associated with an increase in LV end-systolic volume. LV diastolic function impairment was observed without change in LV end-diastolic volume. Respiratory alterations in superior vena cava diameter were never observed, suggesting that volume status remained optimal. Respiratory changes in RV stroke volume were increased according to intraabdominal pressure and body position, reflecting an increase in RV afterload. In conclusion, peritoneal CO2 insufflation in patients scheduled for laparoscopic aortic surgery could impair LV and RV systolic functions as a consequence of increased afterload.

Details of the initial management of cardiac arrest occurring in the workplace in a French urban area.

INTRODUCTION: Our goal was to evaluate the details and management of cardiac arrest (CA) occurring in the working environment. MATERIALS AND METHODS: We conducted a 10-year retrospective study based on the medical records of the Garches mobile intensive care unit. CA occurring in the workplace ("Inside W." group) was matched with two CA outside the workplace ("Outside W." group), with regard to sex, age and year of occurrence. The Chain of Survival and prognosis factors were analysed in a bi-multivariate analysis. RESULTS: From 1993 to 2002, 72 CA were included in the "Inside W." group, with 79% arising from suspected cardiac aetiology (there was a similar proportion in the "Outside W." group). Some variables in the cardiac aetiology patients were higher in the "Inside W." group compared to the "Outside W." group (P < 0.05): early external chest compression [(ECC), 37%, n = 20 versus 16%, n = 16)] and ventricular fibrillation as initial recorded rhythm (40%, n = 33 versus 16%, n = 16). The proportion of use of automated external defibrillator (AED) was similar in the two groups. The workplace was not associated with a better outcome, with 9% patients discharged alive compared to 4% n = 6, P > 0.05. Early ECC and defibrillation attempted with an AED were associated with patients discharged alive from the intensive care unit in a multivariate analysis (P < 0.05), but not the workplace and cardiac aetiology. CONCLUSION: Although our study did not support that concept that the workplace was a safer place, there was a better chain of survival for CA applied within workplace settings. Basic Life Support teaching and installation of AEDs could be helpful, though further cost-effectiveness studies are needed.

Interaction of a combination of morphine and ketamine on the nociceptive flexion reflex in human volunteers.

Experimental studies in animals have suggested that a combination of morphine and N-methyl-D-aspartate (NMDA) receptor antagonists may have additive or synergistic analgesic effects. To further study the nature of the interaction between these two classes of analgesic agents, we analyzed the effects of morphine, ketamine and their combination on electrophysiological recordings of the nociceptive flexion RIII reflex in 12 healthy volunteers. Morphine (0.1 mg/kg), ketamine (0.1 mg/kg followed by 4 microg/kg/min) or their combination were administered intravenously according to a double-blind, placebo controlled and cross-over design. The RIII reflex was recorded from the biceps femoris and elicited by electrical stimulation of the sural nerve. The effects of the drugs were tested on: (1) the stimulus-response curves of the reflex up to the tolerance threshold (frequency of stimulation: 0.1Hz); (2) the progressive increase of the reflex and painful sensations (i.e. wind-up phenomenon) induced by a series of 15 electrical stimuli at a frequency of 1Hz (intensity: 20% above threshold). The stimulus-response curve of the nociceptive RIII reflex was significantly reduced after injection of a combination of ketamine and morphine, but was not modified when placebo or each of the active drugs was administered alone. The wind-up of the RIII reflex and painful sensation was not significantly altered after the injection of placebo, ketamine, morphine or their combination. In conclusion, the present electrophysiological results in humans demonstrate a synergistic interaction between morphine and ketamine, which tends to confirm the interest of using this type of combination in the clinical context. The differential effects observed on the recruitment curve and wind-up indicate, however, that the mechanisms of the interaction between opiates and NMDA receptor antagonists are not univocal but depend on the modality of activation of the nociceptive afferents.

Mild hypothermia does not increase bacterial proliferation on implanted vascular grafts.

BACKGROUND: Mild hypothermia may offer protection against spinal cord ischemia during aortic surgery. However, hypothermia also promotes postoperative infection via two mechanisms: peripheral vasoconstriction and impairment of various immune functions. If mild hypothermia aggravates graft infections, immune function impairment would presumably be the most important factor because thermoregulatory vasoconstriction does not appreciably reduce aortic blood flow. We therefore tested the hypothesis that resistance to vascular graft infection is not reduced by mild perioperative hypothermia in dogs. METHODS: After colonization with a solution of Staphylococcus epidermidis, prostheses were used to replace the infrarenal aorta in 20 dogs. During surgery, the dogs were randomly assigned to maintain of normothermia or passive cooling. Seven days later, grafts were recovered for bacteriologic study. RESULTS: Colony counts for the grafts removed from the normothermic and hypothermic dogs did not differ significantly. CONCLUSIONS: Mild perioperative hypothermia does not increase proliferation of S epidermidis on aortic vascular grafts.

'Boussignac' continuous positive airway pressure system: practical use in a prehospital medical care unit.

Continuous positive airway pressure in acute cardiogenic pulmonary edema is rarely used by prehospital emergency care units, because of the particular technical drawbacks of existing equipment. The aim of this one year prospective descriptive open study without a control group was to assess the technical feasibility of using the Boussignac continuous positive airway pressure system (Vygon) in a prehospital medical care service. Statistical comparisons were performed using Student's t-test or a Wilcoxon T-test. There were 57 decisions to use continuous positive airway pressure. Seven records were excluded. Four patients were intubated on the scene and six within one hour after hospital admission. The respiratory rate and transcutaneous oxygen saturation improved significantly for all of the other patients (Student's t-test P < 0.001). The Boussignac continuous positive airway pressure system has many advantages, including flexibility and pressure monitoring, lower oxygen consumption, and ease of use. These should allow this technique to be used more widely by prehospital teams.

Quality control programme for acute pain management in emergency medicine: a national survey.

OBJECTIVE: This national survey was carried out to evaluate the quality programme for acute pain management in the emergency department (ED) and in pre-hospital emergency medical services (EMS). METHODS: Two types of questionnaires were sent to the chief consultant and the chief nurse of all ED and EMS. Data collected were: the type of structure, quality programme organization, acute pain management, and the training needs to initiate a pain quality programme. RESULTS: A total of 363 questionnaires were recorded (198 from chief consultants) with 98% of questionnaires being usable. A pain management committee existed in 71% of cases, a quality committee in 83%. A complete quality control procedure existed in 53% of units. An audit on pain management was carried out in only 23% of cases. Training in quality was performed for 64% of physicians and 68% of nurses. Training specifically for pain management was carried out for physicians in 56% of cases and for nurses in 68% of cases. Pain therapeutics protocols existed in 69% of cases. Pain intensity was evaluated 'systematically or often' in 64% at the beginning of patient management, and in 56% at the end of patient management. The staff was 'not very motivated' for a pain management quality programme in less than 3% of responses. A total of 61% of chief consultants and 58% of chief nurses requested advice. CONCLUSION: Most ED and EMS units seem to master the quality control programme methodology. Units are highly motivated to initiate a quality control programme on pain. Nevertheless, its implementation could benefit from some external support.

The efficacy of a glial inhibitor, minocycline, for preventing persistent pain after lumbar discectomy: a randomized, double-blind, controlled study.

Minocycline strongly inhibits microglial activation, which contributes to central sensitization, a major mechanism underlying chronic pain development. We hypothesized that the perioperative administration of minocycline might decrease persistent pain after lumbar discectomy. We randomly assigned 100 patients undergoing scheduled lumbar discectomy to placebo and minocycline groups. The minocycline group received 100mg minocycline orally, twice daily, beginning the evening before surgery and continuing for 8 days. The primary outcome was the change in lower limb pain intensity at rest between baseline and 3 months. Secondary outcomes were pain intensity on movement, the incidence of persistent pain and chronic neuropathic pain, back pain intensity at rest and on movement, and changes in Neuropathic Pain Symptom Inventory, Brief Pain Inventory, and Roland-Morris scores at 3 months. An intention-to-treat analysis was performed for patients assessed from the day before surgery to 3 months. The decrease in lower limb pain intensity was similar in the placebo and minocycline groups, both at rest -1.7 ± 1.6 vs -2.3 ± 2.4 and on movement -2.5 ± 2.1 vs -3.4 ± 2.9. The incidence and intensity of neuropathic pain and functional scores did not differ between the minocycline and placebo groups. Exploratory analysis suggested that minocycline might be effective in a subgroup of patients with predominantly deep spontaneous pain at baseline. Perioperative minocycline administration for 8 days does not improve persistent pain after lumbar discectomy.

Risk factors predictive of chronic postsurgical neuropathic pain: the value of the iliac crest bone harvest model.

Nerve lesions and secondary hyperalgesia may both be present after surgery, and their relative contributions to chronic postsurgical neuropathic pain (CPSNP) remain unclear. This prospective study explored the roles of these factors in the development of CPSNP after iliac crest bone harvest. CPSNP was defined as pain in the area of hypoesthesia, with a positive Douleur neuropathique 4 questionnaire (DN4) score 3 months after iliac crest bone harvest. The location, intensity, and neuropathic characteristics of pain were evaluated in 82 patients who were followed for 6 months. Neuropathic characteristics were assessed by clinical examination and DN4 questionnaire. The area of secondary hyperalgesia was evaluated 48 h and 1 month after surgery. The area of mechanical hypoesthesia, detection, and mechanical pain threshold were evaluated at 48 h and at 1 and 3 months. Nineteen patients (23%) had CPSNP at 3 months. The patients who developed CPSNP had a larger area of secondary hyperalgesia at 48 h (88 cm(2) vs 33 cm(2); P=.001), higher pain intensity (numerical rating scale 6.7 vs 4.7; P=.02), and higher neuropathic characteristics score on the DN4 questionnaire (4.3 vs 2.3; P=.001). However, neither the area nor the severity of hypoesthesia differed significantly between patients with and without CPSNP. Two independent, additive predictors of CPSNP were identified: area of secondary hyperalgesia (odds ratio 1.02; P=.004) and DN4 score (odds ratio 1.94; P=.001). These findings suggest that both nerve lesions and central sensitization are involved in CPSNP development and could be seen as early warning signs.

Small fibre impairment predicts neuropathic pain in Guillain-Barré syndrome.

The mechanisms of neuropathic pain (NP) in Guillain Barré syndrome (GBS) are currently unknown. It has recently been shown that acute neuropathy of GBS not only affects large myelinated fibres but also small nociceptive fibres. In this prospective longitudinal 18 months study, we investigated the role of small fibre impairment in NP in GBS (n=30). Small fibres were assessed by quantifying cold and warm detection and pain thresholds and responses to suprathreshold painful thermal and mechanical stimuli. Nerve conduction velocities and mechanical detection thresholds assessed large myelinated fibres. Detection thresholds particularly at the lower limbs were significantly impaired in patients with GBS compared to 15 healthy controls. GBS patients with NP (n=13) had more severe impairment of cold detection thresholds (p=0.04), heat pain thresholds (p=0.03) and responses to suprathreshold heat stimuli (p=0.017) in the foot compared with those without pain or with non-neuropathic pain (n=17). Large fibre dysfunction and motor disability were similar between groups. Small fibre sensory impairment at the acute stage was correlated with the intensity of burning pain (Rho: -0.72; p=0.01 for cold detection; Rho: 0.72; p=0.02 for heat pain) and predicted residual NP (odds 4.1 p=0.04 for heat pain). These findings emphasize the importance of nociceptive fibre impairment in NP in GBS at both acute and chronic stages and suggest similarities between the mechanisms of NP in GBS and those of small fibre painful sensory polyneuropathies.