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N Attal

Publications and source records attributed to N Attal.

At least 19 recordsLinked to original sources
PubMed2006

EFNS guidelines on pharmacological treatment of neuropathic pain.

Neuropathic pain treatment remains unsatisfactory despite a substantial increase in the number of trials. This EFNS Task Force aimed at evaluating the existing evidence about the pharmacological treatment of neuropathic pain. Studies were identified using first the Cochrane Database then Medline. Trials were classified according to the aetiological condition. All class I and II controlled trials (according to EFNS classification of evidence) were assessed, but lower-class studies were considered in conditions that had no top level studies. Only treatments feasible in an outpatient setting were evaluated. Effects on pain symptoms/signs, quality of life and comorbidities were particularly searched for. Most of the randomized controlled trials included patients with postherpetic neuralgia (PHN) and painful polyneuropathies (PPN) mainly caused by diabetes. These trials provide level A evidence for the efficacy of tricyclic antidepressants, gabapentin, pregabalin and opioids, with a large number of class I trials, followed by topical lidocaine (in PHN) and the newer antidepressants venlafaxine and duloxetine (in PPN). A small number of controlled trials were performed in central pain, trigeminal neuralgia, other peripheral neuropathic pain states and multiple-aetiology neuropathic pains. The main peripheral pain conditions respond similarly well to tricyclic antidepressants, gabapentin, and pregabalin, but some conditions, such as HIV-associated polyneuropathy, are more refractory. There are too few studies on central pain, combination therapy, and head-to-head comparison. For future trials, we recommend to assess quality of life and pain symptoms or signs with standardized tools.

AIDS-Associated Nephropathy↗
PubMed2004

Systemic lidocaine in pain due to peripheral nerve injury and predictors of response.

OBJECTIVE: To investigate the effects of IV lidocaine on spontaneous and evoked pain (allodynia and hyperalgesia) due to peripheral nerve injury (postherpetic neuralgia or nerve trauma) using quantitative sensory testing. METHOD: The authors randomized 22 patients to receive lidocaine 5 mg/kg IV during 30 minutes or placebo in a double-blind crossover design and 16 patients subsequently received mexiletine on an open basis titrated from 400 to 1,000 mg per day (mean 737 mg/day). RESULTS: Lidocaine induced a significant decrease in ongoing pain for up to 6 hours with a peak effect 60 to 120 minutes postinjection. The drug also decreased mechanical dynamic allodynia and static (punctate) mechanical allodynia/hyperalgesia, but not thermal allodynia and hyperalgesia. The effects of lidocaine and mexiletine on spontaneous pain intensity were significantly higher in patients with concomitant mechanical allodynia in comparison with those without allodynia. CONCLUSIONS: These data indicate modality-specific antihyperalgesic effects of IV lidocaine in patients with peripheral nerve injury. Patients with mechanical allodynia may be good candidates for treatment with local anesthetic-like drugs and possibly with other sodium-channel blockers.

Adult↗
PubMed2004

[Neuropathic pain: experimental advances and clinical applications].

Neuropathic pain is a clinical entity designating the different types of pain associated with a lesion of the nervous system including a wide range of pathological conditions from painful peripheral lesions (for example diabetic neuropathy, post-zoster pain, trauma-induced nerve injury) and central pain (particularly stroke-induced pain, spinal lesions, and multiple sclerosis). Despite this wide range of etiologies, neuropathic pain has well characterized clinical features which generally allow distinction from other types of pain: continuous often burn-like pain, paroxysmal pain (electrical discharge, knife stab), evoked pain, highly invalidating pain (allodynia, hyperalgesia), and associated dysethesia and/or paresthesia. Over the last ten Years, very little work has been published on neuropathic pain, which is now becoming a very active domain of research in neurobiology. Advances to date have not been spectacular although better tolerated agents have been recently marketed. Future progress should enable an appropriate response to the therapeutic challenge of neuropathic pain.

Animals↗
PubMed2004

Are oral cannabinoids safe and effective in refractory neuropathic pain?

Although cannabinoids have anti-hyperalgesic effects in animal models of nerve injury, there are currently very few prospective trials of the efficacy of cannabinoids in neuropathic pain in humans. This open label prospective study investigated the safety, tolerability and analgesic benefit of oral Delta-9-tetrahydrocannabinol (THC) titrated to a maximal dosage of 25 mg/day in 8 consecutive patients with chronic refractory neuropathic pain. Spontaneous ongoing and paroxysmal pain, allodynia and paresthesias were assessed. The sensory and affective components of pain using the McGill pain questionnaire, quality of life, mood, anxiety and functionality were also evaluated. Seven patients suffered from side effects necessitating premature arrest of the drug in 5 of them. THC (mean dosage: 16.6+/-6.5 mg/day) did not induce any significant effects on ongoing and paroxysmal pain, allodynia, quality of life, anxiety/depression scores and functional impact of pain. These results do not support an overall benefit of THC in pain and quality of life in patients with refractory neuropathic pain.

Administration, Oral↗
PubMed2004

EFNS guidelines on neuropathic pain assessment.

In September 2001, a Task Force was set up under the auspices of the European Federation of Neurological Societies with the aim of evaluating the existing evidence about the methods of assessing neuropathic pain and its treatments. This review led to the development of guidelines to be used in the management of patients with neuropathic pain. In the clinical setting a neurological examination that includes an accurate sensory examination is often sufficient to reach a diagnosis. Nerve conduction studies and somatosensory-evoked potentials, which do not assess small fibre function, may demonstrate and localize a peripheral or central nervous lesion. A quantitative assessment of the nociceptive pathways is provided by quantitative sensory testing and laser-evoked potentials. To evaluate treatment efficacy in a patient and in controlled trials, the simplest psychometric scales and quality of life measures are probably the best methods. A laboratory measure of pain that by-passes the subjective report, and thus cognitive influences, is a hopeful aim for the future.

Europe↗
PubMed2004

Effects of surgery on the sensory deficits of syringomyelia and predictors of outcome: a long term prospective study.

OBJECTIVE: To quantify the effects of surgery on the thermal deficits of syringomyelia and assess the predictors for such effects. METHODS: The subjects were 16 consecutive patients (12 men, 4 women; mean (SD) duration of sensory symptoms, 5.1 (4.5) years) presenting with the typical symptoms of syringomyelia related to Chiari I malformation or trauma, and requiring surgical treatment. They were evaluated before surgery, then at six months and two years. Sensory evaluation included determination of the extent of thermal deficits and quantitative assessment of thermal, mechanical, vibration detection, and pain thresholds. Neuropathic pain intensity was evaluated on visual analogue scales. Magnetic resonance imaging was done before and after surgery to measure syrinx dimensions. RESULTS: The magnitude and extent of thermal deficits improved in a subgroup of patients and this was best predicted by the duration of sensory symptoms: patients operated on less than two years after the onset of their symptoms tended to improve, while those operated on later were stabilised or deteriorated slightly. The effect of surgery on thermal deficits was correlated with the duration of sensory symptoms. Surgery also affected vibration deficits in patients with the Chiari malformation, neuropathic pain on effort, and syrinx dimensions. CONCLUSIONS: The duration of sensory deficits is the best predictive factor of the efficacy of surgery for the thermal symptoms of syringomyelia. Early surgery is required if these deficits are to be minimised.

Adult↗
PubMed2003

Long term effects of oral sustained release morphine on neuropsychological performance in patients with chronic non-cancer pain.

Morphine is increasingly used in patients with chronic non-cancer pain, but a major concern associated with chronic use relates to possible cognitive side-effects. The aim of this long-term prospective study was to evaluate the cognitive impact of oral sustained release morphine in patients with non-cancer pain. A battery of neuropsychological tests to explore attention, psychomotor speed and memory was administered. The effects of morphine on pain, quality of life, mood, subjective memory impairment and side-effects were also investigated. Evaluations were performed at baseline in patients free from opioids and then after 3, 6 and 12 months. Twenty-eight patients were included: 18 received oral sustained morphine (range 40-140 mg/day), ten patients stopped morphine prematurely because of side-effects or insufficient pain relief and were followed as a control group. There was no impairment of any neuropsychological variable over time in the morphine treated patients in comparison with the control group. Two measures of information processing speed - the Stroop interference score and the digit symbol test were improved at 6 and 12 months and there were significant correlations with the pain relief and improvement of mood. Self-reported memory impairment improved notably in responders to morphine. Morphine induced persisting effects on pain, and to a lesser extent on quality of life and mood. The visual analog scale score for side-effects increased at 12 months and essentially consisted of gastrointestinal disorders. This study demonstrates that 12 months treatment with oral morphine does not disrupt cognitive functioning in patients with chronic non-cancer pain and instead results in moderate improvement of some aspects of cognitive functioning, as a consequence of the pain relief and concomitant improvement of well-being and mood.

Administration, Oral↗
PubMed2002

Effects of IV morphine in central pain: a randomized placebo-controlled study.

OBJECTIVE: To investigate the effects of IV morphine on central pain syndromes through quantitative sensory testing and to assess the long-term benefit of oral morphine. METHODS: After an initial open titration phase aiming to determine the maximal tolerated dosage of IV morphine, the efficacy of morphine infusion (9-30 mg; mean dosage, 16 mg) was assessed in a double-blind, placebo-controlled and crossover fashion in 15 patients with poststroke- (6 patients) or spinal cord injury- (9 patients) related pain. All of the patients subsequently received sustained oral morphine. RESULTS: Morphine significantly reduced the intensity of brush-induced allodynia but had no effect on other evoked pains (i.e., static mechanical and thermal allodynia/hyperalgesia). The effects of morphine on ongoing pain were not significantly different from those of the placebo, but 7 patients (46%) responded to morphine. There was a correlation between the effects of morphine on spontaneous pain and the decrease of the responses to suprathreshold thermal stimuli on the nonpainful contralateral side, suggesting that these effects were related to the general antinociceptive activity of the drug. The effects of IV morphine were correlated with those of oral morphine at 1 month, but only 3 patients (20%) were still taking morphine after 1 year. CONCLUSIONS: IV morphine induces analgesic effects on some components of central neuropathic pain syndromes, but only a minority of patients may benefit from long-term opioid treatment.

Adult↗
PubMed2001

Local and remote effects of hypnotic suggestions of analgesia.

The present study was designed to further characterize hypnotic analgesia and particularly to examine whether the effects are due to a selective alteration of pain perception and are organized somatotopically. Thirty-two healthy volunteers participated in this study. Thermal detection thresholds for warmth and cool stimuli and heat pain thresholds were measured at both the upper and lower left limbs by means of a thermotest. Measurements were performed before, during and after a hypnotic session during which the subjects were administered a French adaptation of the Stanford Hypnotic Susceptibility Scale and then standardized suggestions of analgesia limited to the left foot. Heat pain thresholds were significantly increased at both the lower and upper limbs. Changes at the foot were positively correlated with the hypnotic susceptibility score, while, unexpectedly, changes at the hand were negatively correlated with the susceptibility score. Mean detection thresholds for warmth and cool stimuli were also altered at both the lower and upper limbs during hypnosis, but these modifications were correlated neither with susceptibility nor with the changes in heat pain threshold. These results indicate that hypnotic suggestions can selectively and somatotopically alter pain sensation in highly susceptible subjects. It is also suggested, however, that suggestions of analgesia can induce selective alterations of pain perception in poorly susceptible subjects, although these effects did not appear to be localized 'appropriately'.

Adult↗
PubMed2001

Opiate self-administration as a measure of chronic nociceptive pain in arthritic rats.

The study examined the validity of oral fentanyl self-administration (FSA) as a measure of the chronic nociceptive pain that develops in rats with adjuvant arthritis independently of acute noxious challenges. Arthritic rats self-administered more of a 0.008 mg/ml fentanyl solution (up to 3.4 g/rat per day) than non-arthritic controls (0.5 g/rat per day) and did so with a biphasic time course that reached peak during weeks 3 and 4 after inoculation with Mycobacterium butyricum. The time course paralleled both the disease process and the chronic pain. Continuous infusion of dexamethasone during weeks 3 and 4 via subcutaneous osmotic pumps at 0.0025-0.04 mg/rat per day disrupted the arthritic disease and decreased FSA to a level (i.e. by 65%) similar to that observed in non-arthritic rats. Continuous naloxone (2.5 mg/rat per day) decreased FSA (by 55%) in arthritic but not in non-arthritic animals. Continuous, subcutaneous infusion of fentanyl also decreased arthritic FSA in a manner that varied with dose at 0.04-0.16 mg/rat per day doses, but leveled off at 47% of controls with 0.31 mg/rat per day. The effects of continuous fentanyl on arthritic FSA occurred only with those doses and dose-dependent dynamics with which fentanyl also induced dependence in non-arthritic rats. The findings indicate that pain, rather than the rewarding or dependence-inducing action of fentanyl mediates FSA in arthritic rats. Paralleling patient-controlled analgesic drug intake, FSA offers a specific measure allowing the dynamic effects of neurobiological agents to be studied in this unique animal model of persistent nociceptive pain.

Analgesics, Opioid↗
PubMed2001

Pharmacologic treatment of neuropathic pain.

There is currently no consensus concerning the optimal therapeutic strategy for neuropathic pain, despite an increasing number of clinical trials demonstrating successful pain relief with several drugs. Treatments have generally been selected on the basis of evidence for efficacy in randomized placebo-controlled trials conducted in disease-based groups of patients, notably in postherpetic neuralgia and diabetic polyneuropathy. These studies plead in favour of the overall efficacy of tricyclic antidepressants, standard and newer antiepileptics, opioids, tramadol, systemic and topical local anaesthetics, and some NMDA receptor antagonists; whereas evidence for efficacy is less for selective serotonin reuptake inhibitors, antiarrhythmics (mexiletine), and capsaicin. Pharmacological tests, notably therapeutic infusions, have been proposed for predicting the effectiveness of long-term treatments, but are not routinely performed. An analysis of the various neuropathic symptoms, aimed at selecting treatments targeted at mechanisms, may ultimately help the choice of different pharmacologic agents.

Analgesics, Opioid↗
PubMed2000

Intravenous lidocaine in central pain: a double-blind, placebo-controlled, psychophysical study.

OBJECTIVE: To investigate the effects of systemic administration of lidocaine on different components of neuropathic central pains by quantitative sensory testing. METHODS: The efficacy of systemic lidocaine (5 mg/kg IV over 30 minutes) was evaluated in a double-blind, placebo-controlled, and cross-over fashion, on both spontaneous ongoing pain and evoked pains (allodynia and hyperalgesia) in 16 patients with chronic poststroke (n = 6) or spinal cord injury (n = 10) related pain. RESULTS: Lidocaine was significantly superior to the placebo (saline) in reducing the intensity of spontaneous ongoing pain for up to 45 minutes after the injection: 10 of 16 patients (62.5%) receiving lidocaine showed a significant reduction in spontaneous pain, whereas only six patients showed this after the placebo. Lidocaine also significantly reduced the intensity of brush-induced allodynia and mechanical hyperalgesia, but was no better than the placebo against thermal allodynia and hyperalgesia. In general, the side effects were moderate and consisted mainly of lightheadedness (44%). CONCLUSIONS: Systemic lidocaine can induce a significant and selective reduction of several components of pain caused by CNS injuries. The observed preferential antihyperalgesic and antiallodynic effects of this drug suggest a selective central action on the mechanisms underlying these evoked pains.

Adult↗
PubMed2000

Chronic neuropathic pain: mechanisms and treatment.

There have been considerable advances in our understanding of the pathophysiology of neuropathic pain. There is still a lack of consensus about the optimal therapeutic strategy of such conditions, however. Drugs are generally selected on the basis of their established efficacy in randomized controlled studies in etiologically based groups of patients. These studies have been important in confirming the efficacy of antidepressants, antiepileptics, local anesthetics and derivatives, capsaicin, opioids, and N-methyl-D-aspartate antagonists in neuropathic pain, specifically painful diabetic neuropathy and postherpetic neuralgia. More specific therapeutic strategies based on precise quantified assessment of the various components of neuropathic pain are now increasingly used and may provide insight regarding the effects of treatments of particular symptoms (e.g., allodynia, hyperalgesia). In some cases, such assessment may also help to analyze the mechanisms involved in pain, thus allowing selection of treatment on a more rational basis. A mechanism-based approach seems promising for clinical research studies, although its application in current management remains challenging.

Chronic Disease↗
PubMed2000

[Recent pharmacologic approaches to pain].

The identification of compounds that can effectively and safely treat chronic pain is a major challenge of biomedical research. One approach is to optimize currently active analgesic treatments, notably by reducing their side effects. An example of this approach is the recent development of a novel class of nonsteroidal antiinflammatory drugs (NSAIDs), the cyclo-oxygenase 2 inhibitors, that lack the limiting gastrointestinal side effects of the traditional NSAIDs. Another approach, based on the recent development of molecular biology, is to develop analgesic compounds acting on new targets. These include notably ion channel blockers (TTX-resistant sodium channel blockers specific for nociceptors, N-type calcium channel blockers), nicotine receptor agonists, peptide receptor antagonists, N-methyl-D-aspartate (NMDA) receptor antagonists, vanilloids, new opioid compounds, cannabinoids, selective alpha2-adrergic agonists, purinergic modulators. Most of these compounds are currently in preclinical or early clinical investigation. However, the development of more predictable in vitro and in vivo tests and the broadening use of clinical models of experimental pain, will hopefully help increase the proportion of drugs that will become successful analgesics in clinical practice.

Analgesics↗
PubMed1999

Painful and painless peripheral sensory neuropathies due to HIV infection: a comparison using quantitative sensory evaluation.

In order to characterize further, sensory disorders due to HIV-induced distal symmetrical polyneuropathy (DSPN), we compared quantitative sensory testing (QST) and electrodiagnostic parameters in patients presenting with painful or painless DSPN. Forty HIV patients with DSPN were studied and compared with ten seronegative control subjects: 15 patients presented with pains (spontaneous and/or evoked) in the lower limbs and 25 patients, matched for age, sex, duration of HIV and CD4 count, had non-painful symptoms (i.e. paresthesia). QST and nerve conduction studies (NCS) were performed on the lower limbs. von Frey hairs and a thermotest device were used to determine the mechanical- and thermal-, detection and pain thresholds. The responses elicited by suprathreshold thermal and mechanical stimuli were measured on a visual analog scale (VAS), to evaluate hyperalgesia. NCS were not significantly different between the two groups of patients. Thermal and mechanical detection thresholds, as well as the thermal pain threshold were significantly, and similarly, increased in both groups of patients as compared with the normal control subjects. Responses to suprathreshold thermal stimuli were similar in patients and control subjects. In contrast, mechanical pain thresholds were significantly decreased (mechanical allodynia) and responses to suprathreshold mechanical stimuli significantly increased (mechanical hyperalgesia) in the pain, but not in the painless patients. The intensity of mechanical allodynia/hyperalgesia was correlated with the intensity of spontaneous ongoing pain. We conclude that patients with DSPN are characterized by thermal, mechanical and electrophysiological deficits, suggestive of alterations in both small and large peripheral nerve fibers. Patients with a painful neuropathy present with static mechanical allodynia/hyperalgesia, suggestive of a selective alteration in the processing of mechanoreceptive signals, which might have a significant role in the pathophysiology of spontaneous and evoked pains in these patients.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Effects of single and repeated applications of a eutectic mixture of local anaesthetics (EMLA) cream on spontaneous and evoked pain in post-herpetic neuralgia.

The analgesic effects of single and repeated applications of a eutectic mixture of local anaesthetics (EMLA) cream on both spontaneous and evoked pains were evaluated in 11 patients with post-herpetic neuralgia (PHN). Detection thresholds, pain thresholds and the responses to suprathreshold mechanical and thermal stimuli were quantitatively determined at baseline, 30 min after the first application and after a series of daily applications over six consecutive days (duration of application: 5 h/day). In the acute situation, EMLA produced an overall anaesthetic effect without significantly reducing spontaneous ongoing pain and mechanical allodynia. Repeated applications significantly reduced paroxysmal pain and both the dynamic and static subtypes of mechanical hyperalgesia. The effects on spontaneous ongoing pain were more variable. They were inversely correlated to the magnitude of the thermal deficit at baseline, and were significant only in patients with dynamic mechano-allodynia. Pathophysiological implications of these results are discussed.

Aged↗
PubMed1999

Carbamazepine in agitation and aggressive behaviour following severe closed-head injury: results of an open trial.

Ten patients presenting agitation and anger outbursts at various stages following a severe closed head injury, were treated in a prospective open trial with carbamazepine, with doses ranging from 400 to 800 mg per day, during 8 weeks. Group analysis demonstrated a statistically significant improvement of a score made up from six target items from the neurobehavioural rating scale. Improvement mainly concerned irritability and disinhibition. A statistically significant improvement was also found with the Agitated Behaviour Scale. Social functioning, as assessed by family or staff ratings of the Katz Adjustment Scale, also significantly improved. No modification of global cognitive functioning was found with the Mini Mental Status Examination. Individual analysis demonstrated that the beneficial effect was important in five cases, moderate in three patients and negligible in two cases. It is concluded that carbamazepine might help to reduce agitated behaviour in brain-injured patients. However, response to treatment demonstrated an important inter-individual variability.

Adult↗