Management of neuropathic pain induced by surgery: Review of the literature by a group of experts specialized in pain management, anesthesia and surgery.

Chronic postsurgical neuropathic pain (CPSNP) is frequent. While prevalence varies considerably according to type of operation and means of evaluation, it can reach 37% following breast surgery. Identification of risk factors related to the procedure and to the patient and taking into account the development of new, minimally invasive surgical techniques is increasingly nerve-sparing and reduces the likelihood of injury. CPSNP diagnosis in daily practice is facilitated by simple and quickly usable tools such as the NP4 4-question test. Management is based on pharmacological (analgesics, antiepileptics, antidepressants, local anesthetics) and non-pharmacological (kinesitherapy, neurostimulation, psychotherapy) approaches. In light of the present review of the literature, the authors, who constitute an expert group specialized in pain management, anesthesia and surgery, express their support for topical treatments (lidocaine, capsaicin) in treatment of localized postsurgical neuropathic pain in adults.

Multicolumn spinal cord stimulation for significant low back pain in failed back surgery syndrome: design of a national, multicentre, randomized, controlled health economics trial (ESTIMET Study).

BACKGROUND: Many studies have demonstrated the efficacy of spinal cord stimulation (SCS) for chronic neuropathic radicular pain over recent decades, but despite global favourable outcomes in failed back surgery syndrome (FBSS) with leg pain, the back pain component remains poorly controlled by neurostimulation. Technological and scientific progress has led to the development of new SCS leads, comprising a multicolumn design and a greater number of contacts. The efficacy of multicolumn SCS lead configurations for the treatment of the back pain component of FBSS has recently been suggested by pilot studies. However, a randomized controlled trial must be conducted to confirm the efficacy of new generation multicolumn SCS. Évaluation médico-économique de la STImulation MEdullaire mulTi-colonnes (ESTIMET) is a multicentre, randomized study designed to compare the clinical efficacy and health economics aspects of mono- vs. multicolumn SCS lead programming in FBSS patients with radicular pain and significant back pain. MATERIALS AND METHODS: FBSS patients with a radicular pain VAS score≥50mm, associated with a significant back pain component were recruited in 14 centres in France and implanted with multicolumn SCS. Before the lead implantation procedure, they were 1:1 randomized to monocolumn SCS (group 1) or multicolumn SCS (group 2). Programming was performed using only one column for group 1 and full use of the 3 columns for group 2. Outcome assessment was performed at baseline (pre-implantation), and 1, 3, 6 and 12months post-implantation. The primary outcome measure was a reduction of the severity of low back pain (bVAS reduction≥50%) at the 6-month visit. Additional outcome measures were changes in global pain, leg pain, paraesthesia coverage mapping, functional capacities, quality of life, neuropsychological aspects, patient satisfaction and healthcare resource consumption. TRIAL STATUS: Trial recruitment started in May 2012. As of September 2013, all 14 study centres have been initiated and 112/115 patients have been enrolled. Preliminary results are expected to be published in 2015. TRIAL REGISTRATION: Clinical trial registration information-URL: www.clinicaltrials.gov. Unique identifier NCT01628237.

Challenges in the optimisation of post-operative pain management with opioids in obese patients: a literature review.

An increasing number of obese patients are undergoing surgery, particularly bariatric and orthopaedic surgery. The physiological differences between obese and normal-weight subjects may modify not only anaesthetic requirements during surgery but also post-operative analgesic management, raising a number of challenges in a critical period. In this review, we analyse studies of post-operative pain management with opioids in obese subjects. We discuss the genetic factors common to pain and obesity and the factors potentially modifying opioid pharmacokinetics and pharmacodynamics in obese patients, and we analyse the overall efficacy and safety of opioids for pain management during the post-operative period in obese patients. Both modifications to surgical methods and additional analgesic treatments to decrease the requirement for opioids may improve early rehabilitation and quality of care and reduce adverse effects in obese patients.

Epidemiological data, efficacy and safety of a paracetamol-tramadol fixed combination in the treatment of moderate-to-severe pain. SALZA: a post-marketing study in general practice.

OBJECTIVE: To evaluate the efficacy and safety of the paracetamol-tramadol combination (PTC) in treating moderate-to-severe pain, in patients aged 65 years and over within general practitioner (GP) practice centers. RESEARCH DESIGN AND METHODS: This was an observational, non-interventional, longitudinal, multicenter, open, non-comparative, prospective study. This intermediary analysis was of patients recruited before the French Health Authority confirmation (25th June, 2009) of the EMEA decision to withdraw all analgesics containing dextropropoxyphen. Trial registration information: This study has been submitted for approval to the CNIL and French Medical Council (CNOM) only. RESULTS: A total of 2663 patients aged 65 years or over were assessed 1 month after inclusion in the study. PTC was prescribed as first-line treatment in 30% of patients and, in the other cases, after failed or inadequate efficacy (69.8%), and/or as a result of safety problems (7.8%) with at least one other analgesic. During the month of the study period 14.7% of patients received an additional rescue analgesic. The study confirmed the efficacy of PTC with regard to pain intensity (-3.1 points reduction of pain scored 6.1 points on inclusion), pain relief (64.8% of patients experienced significant pain relief), patient satisfaction (90.5% of patients satisfied or completely satisfied) and clinical global impression evaluated by the patient (78.7% much or very much improved), regardless of the pain etiologies or duration of the underlying pathology. PTC was well-tolerated in this patient group, who had a mean age of 73.6 ± 6.6 years. A total of 119 patients (4.5%) reported at least one adverse event (AE). All were known and predictable AEs. This percentage is comparable to that found under similar conditions in patients of all ages (4.2%). CONCLUSIONS: PTC, due to the complementary action of its two analgesics, is effective in treating the different types of pain in a GP's practice setting and is well-tolerated, even in an elderly population. Study limitations include all those inherent to non-interventional and open-label observations.

[Cranial nerve functional neurosurgery: evaluation of surgical practice]. / La neurochirurgie fonctionnelle des nerfs crâniens Evaluation de l'activité

We report the results of an investigation carried out on the activity of functional neurosurgery of the cranial nerves in the French-speaking countries, based on the analysis of a questionnaire addressed to all the members of the SNCLF. Eighteen centers responded to this questionnaire, which showed that activities and indications varied greatly from one unit to another. The results appear homogeneous and comparable with those reported in the literature. The questionnaire sought to provide a global perspective, open to the comments and questions of all responders on the various techniques raised, with the objective of establishing a common decisional tree for these pathologies and providing if possible to a consensus for better dissemination of these therapies.

Active or passive pain coping strategies in hip and knee osteoarthritis? Results of a national survey of 4,719 patients in a primary care setting.

OBJECTIVE: To study pain coping strategies in patients with hip and knee osteoarthritis (OA), and to assess the psychometric qualities of the French version of the Pain Coping Inventory (PCI). METHODS: We conducted a national, cross-sectional survey in a primary care setting in France. A total of 1,811 general practitioners included 5,324 patients with hip and knee OA who completed several questionnaires, including the PCI, which assesses ability to cope with pain. RESULTS: The records of 4,719 (86.4%) patients were analyzed (knee 2,781; hip 1,553; hip and knee 385). Supporting the structure of the original questionnaire, we found that the 33 PCI questionnaire items could be grouped into 3 domains defining active coping strategies and 3 defining passive coping strategies. Acceptable convergent validity was found for the PCI (Cronbach's alpha coefficient for each domain >0.68). Coping strategy scores were significantly higher in patients with both knee and hip involvement (mean +/- SD 2.3 +/- 0.4) than for patients with OA at 1 site (mean +/- SD 2.1 +/- 0.4), and in women compared with men (P < 0.001). The use of passive pain coping strategies increased with OA duration, and was greater in older and overweight patients, in patients with no current physical activity or major impairment, in retired and nonworking patients, and in patients who were not married, and to a lesser extent in patients with higher pain intensity. Compared with previous data, patients with OA demonstrated lower active and higher passive strategies than patients with rheumatoid arthritis and other chronic painful conditions. CONCLUSION: The PCI has good structural validity and is highly suitable for analyzing active and passive pain coping strategies in OA. In OA, active and passive coping strategies differ significantly as a function of age, body mass index, OA involvement, professional and marital status, sport activities, and OA duration, with pain intensity having a weaker effect.

[Pain management: a priority for public health]. / Prise en charge de la douleur : une priorité de santé publique.

In France, the actual anti-pain triennial plan (1998-2000) combines: the listening and the follow-up of the patient, the reinforcement of the fight against pain in health structures and care networks, the permanent information of medical and paramedical staffs, the information of the public.

Acute decreases in cerebrospinal fluid glutathione levels after intracerebroventricular morphine for cancer pain.

UNLABELLED: Intracerebroventricular (ICV) morphine administration is effective for the management of refractory cancer pain. Recent preclinical observations of acute depletion of the major endogenous intracellular antioxidant glutathione (GSH) in brain and peripheral organs after ICV morphine in rodents led us to apply microchemical methods to profile the neurochemical effects of ICV morphine in three patients treated for intractable cancer pain. Assessment of morphine, morphine-6-glucuronide, and a panel of endogenous compounds and metabolites in ventricular and cisternal cerebrospinal fluid (CSF) demonstrated transient, postdose increases in morphine and morphine-6-glucuronide in ventricular and cistemal CSF, accompanied by acute decreases in CSF GSH levels. Significant changes were also observed in the CSF levels of 4-hydroxybenzoic acid, homovanillic acid, 5-hydroxyphenyllactic acid, and uric acid. These pilot clinical observations of acute central GSH depletion after ICV morphine suggest a novel mechanism for neuropsychiatric toxicity or preclinical findings, such as hyperalgesia or increased motoric activity observed in nonhuman species after central morphine administration. Because ICV morphine is a mainstay of treatment for refractory cancer pain, elucidation of a mechanism's (or mechanisms') mediating a potential pro-oxidant state in the central nervous system induced by ICV morphine is important. IMPLICATIONS: We observed acute decreases in glutathione levels in cerebrospinal fluid sampled from patients after intracerebroventricular doses of morphine for intractable cancer pain. Such doses may, by depleting the antioxidant glutathione, render the central nervous system vulnerable to damage from oxidative stress.

[Analgesic effect of morphine and its metabolites administered by an intracerebroventricular route]. / Etudes de l'effet analgésique de la morphine et de ses métabolites administrés par voie intracérébro-ventriculaire.

Intraventricular morphine administration is indicated, in some selected cases, to alleviate intractable cancer pain. Our pharmacokinetics data in cerebro-spinal fluid allowed us to formulate the theory of "Front de Recrutement". Then we were able to determine in cisternal and ventricular cerebrospinal fluid the morphine 6-glucuronide concentrations. Morphine 6-glucuronide is the main analgesic metabolite of morphine and its presence in cerebro-spinal fluid could be due to a metabolism of morphine in the central nervous system. Our animal studies showed that the analgesic activity of morphine 6-glucuronide was 27 to 67 times higher than that of morphine. By demonstrating the 6-monoacetyl morphine potency (analgesic metabolite of heroin that is 20 times more potent than morphine), we showed the involvement of the 6 position in the analgesic effect of these opioids. When we compared the morphine-6 concentrations in human cerebro-spinal fluid with the analgesic potency of this metabolite, the morphine-6 glucuronide was responsible of 33% to 67% of the supra-spinal analgesic effect. As heroin, morphine must be considered as a precursor whose metabolites have pharmacologic effects.

[Benign chronic pain]. / Les douleurs chroniques bénignes.

Recent data indicate that 25 to 30% of the population in industrialized countries suffers from benign chronic pain. Among these patients, 50 to 75% are professionally incapable for varied lengths of time, from a few days to some weeks or months, or even definitively. The aetiology and clinical presentation of chronic benign pain are enormously varied because this definition includes such different pathologies as headache, pain of rheumatologic, postsurgical, organic, and post-zoster origin, lombalgia, radiculalgia, post-amputation pain, neuropathologic pain, causalgia, algoneurodystrophic pain, psychosomatic and idiopathic pain. Since these syndromes and causes of pain could not be discussed individually, they have been grouped according to their neurophysiology and pathophysiology.

Enhanced potency of intravenous, but not intrathecal, morphine and morphine-6-glucuronide after burn trauma.

We examined the analgesic effect of morphine (M) and its metabolite morphine-6-glucuronide (M6G) in a rat model of acute thermal trauma. M or M6G were given by intrathecal (IT) or intravenous (i.v.) routes after brief burn or sham burn delivered during inhalational anesthesia. In the sham group, M6G was significantly less potent than M when given i.v., yet tended to be more potent than M when given IT. For both drugs, thermal injury increased i.v. potency, yet decreased (for M) or displayed a trend to decrease (for M6G) It potency. The increased potency seen with i.v. but not IT opioid administration may reflect pharmacokinetic (e.g., diminished clearance) and/or pharmacodynamic responses (e.g., activation of peripheral opioid receptors) after thermal injury.

Cerebral vasodilation after the thermocoagulation of the trigeminal ganglion in humans.

The resulting changes in the regional cerebral blood flow of 18 patients suffering from idiopathic trigeminal neuralgia and treated by selective thermocoagulation of the trigeminal ganglion were measured by xenon-133 emission tomography. One hour after thermal stimulation, there was an asymmetric increase (P < 0.05) in cerebral blood flow, with a 14.7% mean increase in the ipsilateral cerebral hemisphere (P < 0.001) and a 12.7% mean increase in the contralateral side (P < 0.01). The increase in regional cerebral blood flow was not uniform but was most marked in the ipsilateral middle cerebral artery territory (P < 0.001). There was a slight decrease in cerebellar blood flow, but the reduction in the ipsilateral cerebellar lobe was less than that in the contralateral lobe (P < 0.01). The topography of the most significant changes coincided with that of the innervation of the cerebral vessels by the trigeminal nerve. Several mechanisms are involved in the increase in regional cerebral blood flow, including overall nonspecific activation of the central nervous system and local mechanisms associated with the trigeminal-vascular system.

Morphine pharmacokinetics and pain assessment after intracerebroventricular administration in patients with terminal cancer.

Morphine pharmacokinetics and pain relief were evaluated after intracerebroventricular administration of morphine (0.4 +/- 0.11 mg) in seven patients with cancer suffering from intractable pain. Ventricular cerebrospinal fluid (CSF), lumbar CSF, and plasma morphine concentrations were analyzed by a specific morphine radioimmunoassay. A two-compartment model was sufficient to describe the kinetics of morphine in ventricular CSF. Morphine diffuses to the lumbar level, and the mean maximum concentration was 192 +/- 105 ng/ml at 4.5 +/- 1.3 hours. Ventricular and lumbar CSF morphine kinetics showed a similar decline during the elimination phase, with terminal half-lives of 3.8 +/- 0.6 hours and 4.2 +/- 1.6 hours, respectively. Pain relief was evaluated by a visual analog scale: the test showed a rapid onset of analgesia (less than 10 minutes). Analgesic effectiveness reached a maximum between 6 and 10 hours. The relationship between pharmacologic effect and morphine concentrations in ventricular CSF resulted in an anticlockwise hysteresis curve. The presence of morphine in lumbar CSF suggested an additive spinal action of morphine, which probably plays a role in the duration of analgesia.

Levels of morphine and metabolites in CSF during respiratory depression after intraventricular morphine injection.

We report a case of respiratory depression after intracerebroventricular morphine administration of a dose inadvertently 10 times greater than the typical daily dose. At the time of the respiratory dysfunction, the concentrations of morphine and its metabolites in cerebrospinal fluid (CSF) and plasma samples were determined. On comparison of these results with previous clinical studies in which there was no respiratory depression, no relationship was found between the occurrence of respiratory depression and the concentration of morphine or its metabolites in the CSF. The occurrence and characteristics of respiratory depression may be related to the concentrations of morphine and its metabolites in bulbar tissue.