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Biomedical subjects

N Attal

Publications and source records attributed to N Attal.

At least 37 records · Page 2Linked to original sources
PubMed1999

Mechanisms of pain in peripheral neuropathy.

Over the last few years, the mechanisms of pain due to peripheral nerve injury have been the subject of extensive clinical and fundamental investigation. Several types of peripheral mechanisms have been described in animal models of peripheral nerve injury. Abnormal (ectopic) neuronal activity has been reported in primary afferents and in the dorsal root ganglion, and appears related to dysregulation of the synthesis and/or the functioning of sodium channels (notably the tetrodotoxin-resistant channel). Fiber interactions (ephaptic or cross-excitation), nociceptor sensitization and sympathetic sensory coupling may also be involved in some cases. Peripheral nerve lesions can also induce central changes; this has essentially been investigated at the spinal cord level in animals. Three major types of modifications could induce a pathologic activation of central nociceptive neurons: modification of the modulatory controls of the transmission of nociceptive messages; anatomic reorganization (neuroplasticity) of the central nociceptive neurons, and thus their pathologic activation; and central sensitization (hyperexcitability) of nociceptive neurons to produce modifications of their electrophysiologic properties. Central sensitization probably depends critically on intracellular changes induced by the activation of N-methyl-D-aspartate (NMDA) receptors by excitatory amino acids released by primary afferents. Due to the multiplicity of mechanisms, it is unlikely that neuropathic pain corresponds to a unique entity. Each of the painful symptoms may correspond to distinct mechanisms and thus respond to specific treatments.

Animals↗
PubMed1999

[Characterization of sensation disorders and neuropathic pain related to syringomyelia. A prospective study].

The present prospective study aimed to perform quantitative sensory testing (QST) in patients with painful or painless syringomyelia before and after surgical treatment of their syrinx (at 3 and 9 months). Eighteen consecutive patients with cervical or dorso-lumbar syringomyelia completed the study and 9 underwent surgery. Twelve patients had central neuropathic pain (of whom 6 were followed up). Spontaneous pain and brush-evoked allodynia were assessed. Von Frey hairs, vibrameter and a thermotest device were used to determine the mechanical-, vibratory-, thermal-detection thresholds, and the mechanical and thermal pain thresholds. Results showed evidence of deficits in temperature and pain sensibility in 17 cases, often associated with deficits in vibration and touch sensitivity (11 cases). Magnetic resonance scan, including axial images, demonstrated good correlation between paramedian extension of the syrinx and the laterality of thermal deficits. Somatosensory evoked potentials (11 patients) were abnormal in 9 cases at level, and showed good correlation with deficits in vibration. The magnitude of the thermal and tactile deficit was similar between areas of spontaneous pain and adjacent non painful areas. Surgery induced a significant decrease of tactile deficits, and to a lesser extent, of thermal deficits. Effects on neuropathic pain were positive in 3 patients (total disappearance of pain) and negligible or negative in 3 patients, despite collapse of the syrinx (in 2 cases). These results confirm that QST are useful in clinical practice to quantify the clinical results of surgery in patients with syringomyelia, and allow some hypotheses about the mechanisms of neuropathic pain in these patients.

Adult↗
PubMed1998

A case of 'pure' dynamic mechano-allodynia due to a lesion of the spinal cord: pathophysiological considerations.

We report the unusual observation of a patient who presented with the single symptom of a very intense, brush-induced allodynia (dynamic mechanical allodynia) which was strictly confined to the left C2 and C3 dermatomes. All investigations, including a cervical spinal MRI, were initially normal. The clinical picture remained stable for several months until the appearance of spontaneous pain and sensory deficits suggestive of a spinal lesion. A second MRI revealed an intraspinal lesion involving the C2-C5 segments. In accordance with other clinical and animal studies, such an observation of a 'pure' dynamic mechano-allodynia suggests that specific mechanisms underlie each component of neuropathic pain. Possible pathophysiological mechanisms are discussed in the light of recent experimental results obtained in animals.

Aged↗
PubMed1998

Effects of gabapentin on the different components of peripheral and central neuropathic pain syndromes: a pilot study.

Anticonvulsants are widely used in the treatment of neuropathic pain, and are assumed to act preferentially on lancinating, shooting pain. In the present study, the effects of gabapentin, a novel anticonvulsant, were evaluated systematically on both spontaneous and evoked pain in 18 patients with peripheral nerve injuries or central lesions. Gabapentin was administered orally in gradually increasing doses up to a maximum of 2,400 mg/day. Evaluations of spontaneous ongoing and paroxysmal pain, allodynia and hyperalgesia were performed at the beginning of the study ('baseline') and 6 weeks after the steady-state dose had been reached. Quantitative sensory tests were used to measure detection and pain thresholds to mechanical and thermal stimuli and the responses to suprathreshold stimuli. Gabapentin induced a moderate and statistically significant relief of ongoing spontaneous pain and was particularly effective in reducing paroxysmal pain. A striking finding was the significant effect on brush-induced and cold allodynia. In contrast, no effects were observed on detection and pain thresholds to static mechanical and hot stimuli. Side effects were generally minor and did not interfere with everyday activities. The present study suggests that gabapentin has preferential antihyperalgesic and/or antiallodynic effects, and is equally effective in pain due to peripheral nerve injuries and central lesions.

Acetates↗
PubMed1995

Excessive glutamine sensitivity in Alzheimer's disease and Down syndrome lymphocytes.

In addition to clinical and neuropathological similarities between Alzheimer's disease and Down syndrome there are genetic and biochemical data which suggest common disease mechanism. Using an in vitro assay examining variations of the mitotic index in the presence or absence of various inhibitors or metabolites of purine and/or pyrimidine synthesis, we studied 19 Alzheimer disease patients and 16 patients with both Down syndrome and Alzheimer type dementia. A highly significant decrease in mitotic index in the presence of exogenous glutamine was noted in patients presenting an Alzheimer type dementia with or without associated Down syndrome. These findings suggest that glutamine sensitivity or some dysregulation of the glutamine/glutamate pathway may play a role in the pathogenesis of Alzheimer's disease. If these findings are confirmed, they would have important implications in the development of preventive strategies.

Adult↗
PubMed1994

Behavioural pain-related disorders and contribution of the saphenous nerve in crush and chronic constriction injury of the rat sciatic nerve.

This study evaluated the pain-related behaviours induced by 2 models of peripheral sciatic nerve injuries in the rat: transient nerve crush and chronic constriction injury (CCI). Various lesions of the saphenous nerve were performed in order to investigate the role of saphenous innervation in behavioural disorders induced by these nerve injuries. Behavioural testing included assessment of responses to phasic stimulation (mechanical and thermal) and observation of 'spontaneous' pain-related behaviour. Results confirmed that the model of CCI induces marked and prolonged phasic and spontaneous pain-related disorders (up to week 7). Rats with crush injury exhibited moderate and transient hyperalgesia and allodynia to mechanical and thermal stimulation on the lesioned side (with a maximum at day 3 and a recovery by week 1). Section plus ligation of the ipsilateral saphenous nerve on the day of surgery prevented nociceptive behaviours and induced persistent mechanical and thermal anaesthesia or hypoesthesia of the lesioned paw in both models (lasting up to 3-4 weeks). Section without ligation of the saphenous nerve induced comparable results in rats with sciatic crush, but did not significantly modify nociceptive behaviours in rats with CCI. These data emphasise the role of adjacent saphenous nerve in the mechanisms of pain-related disorders induced by these peripheral nerve lesions. On the contralateral paw, pain-related modifications were also observed in both models, suggesting that unilateral nerve lesions induce remote modifications extending beyond the site of the injured nerve.

Animals↗
PubMed1994

"SUNCT" syndrome. A case of transformation from trigeminal neuralgia?

A patient with typical trigeminal neuralgia involving the first branch of the nerve developed short-lasting unilateral attacks in the same area which were associated with severe vasomotor phenomena consistent with the recently described SUNCT syndrome. This evolution suggests that SUNCT might correspond, at least in this case, to a "transformed" trigeminal neuralgia and emphasizes the close relationship between these unilateral facial pain syndromes.

Cerebrospinal Fluid Rhinorrhea↗
PubMed1993

Are mechanical and cold allodynia in mononeuropathic and arthritic rats relieved by systemic treatment with calcitonin or guanethidine?

The putative antinociceptive action of guanethidine and calcitonin systemically injected has been compared in 2 rat models of persistent experimental pain: Freund's adjuvant-induced arthritis (n = 29) and mononeuropathy induced by 4 loose ligatures around the sciatic nerve (n = 24). Guanethidine (30 mg/kg, i.v.) and calcitonin (0.125 mg, s.c.) were injected once a day over 1 week, when hyperalgesia was fully developed. The antinociceptive action was gauged using nociceptive tests based on mechanical or cold stimuli (vocalization threshold to paw pressure and struggle latency to 10 degrees C, respectively), and the score of spontaneous pain-related behavior was measured on the basis of the abnormal hind paw position. No antinociceptive action was observed in calcitonin-compared to saline-injected rats, either in arthritic or neuropathic animals. Guanethidine treatment was ineffective on hyperalgesia exhibited in arthritic rats but was able to reduce reliably and even suppress the abnormal reactions to cold stimulus in neuropathic animals. The lack of hypoalgesic action of calcitonin versus its beneficial action in bone repair, as well as the possible role(s) of the sympathetic system in neuropathic versus arthritic pain and in hyperalgesia versus physical signs of inflammation, are discussed.

Animals↗
PubMed1992

Lesions of basal ganglia due to disulfiram neurotoxicity.

Three cases of disulfiram induced Parkinsonism and frontal lobe-like syndrome associated with bilateral lesions of the lentiform nuclei on CT scan are reported. Symptoms developed either after an acute high dose of disulfiram (one case) or after several days to weeks of disulfiram treatment (two cases) and persisted over several years in two patients. These observations suggest that basal ganglia are one of the major targets of disulfiram neurotoxicity. The mechanisms of the lesions of basal ganglia may involve carbon disulfide toxicity.

Adult↗
PubMed1992

[Dementia disclosing primary Gougerot-Sjögren syndrome].

Two cases of primary Sjögren's syndrome revealed by dementia are reported. The patients had progressive or subacute memory dysfunction and psychiatric disorders with depression and delirium. The diagnosis of Sjögren's syndrome was established by biopsy of the minor salivary glands. Both patients were treated with corticosteroids. The neuropsychiatric symptoms improved dramatically in one case and remained unchanged in the other case. Dementia in Sjögren's syndrome seems to be without aphasia, apraxia or agnosia, and associated with psychiatric features, particularly depressive symptoms, thus including some characteristics of subcortical dementia. Diagnosis may be difficult because, as shown in our cases, symptoms of ocular and buccal dryness can be absent. Salivary gland biopsy can be useful in the evaluation of patients with dementia of undetermined etiology.

Biopsy↗
PubMed1991

Effects of guanethidine on sensitization to natural stimuli and self-mutilating behaviour in rats with a peripheral neuropathy.

In the present study we have used a recent rat model for neuropathic pain to investigate the effect of the sympatholytic drug guanethidine on changes in behavioural responses evoked by mechanical, heat and cold stimuli and on self-mutilating behaviour. After a unilateral peripheral mononeuropathy induced by ligatures around the right common sciatic nerve, the left side receiving just a sham wound, lesioned and non-operated control animals were treated with saline or guanethidine (30 mg/kg) for 4 consecutive days commencing 5 days before or 10 days after surgery. Behavioural parameters were followed for 4 weeks after drug treatment. Lesioned rats were found to be sensitized to the otherwise innocuous cold stimulus and showed decreased response thresholds to noxious heat and mechanical stimuli. Some lesioned animals self-mutilated. Treatment with guanethidine diminished heat and cold sensitization considerably, but had less effect on mechanical sensitization and, if administered before surgery, rather increased the severity of self-mutilating behaviour. While these results are in agreement with clinical observations on the prominence of sensitization to evoked stimuli, especially cold, and the effectiveness of guanethidine in sympathetically maintained neuropathic pain, they indicate that the mechanisms involved in sensitization to different stimuli and self mutilating behaviour differ.

Animals↗
PubMed1991

Single neurone studies of opioid tolerance and dependence at the ventrobasal thalamic level in an experimental model of clinical pain, the arthritic rat.

The aim of this electrophysiological study was to investigate the effects of an acute injection of morphine (1 mg/kg i.v.) or the opioid antagonist naloxone (0.6-2 mg/kg i.v.) on thalamic ventrobasal (VB) neuronal activities recorded in arthritic rats rendered tolerant/dependent by pretreatment with relatively low doses of morphine. Recordings were performed in animals immobilized by i.v. injections of gallamine triethiodide (Flaxedil) and artificially ventilated under a moderate gaseous anesthesia (mixture of one-third O2, two-thirds N2O, 0.5-0.6% halothane). This level of anesthesia, as checked by the electrocorticogram, was stable and appeared sufficiently deep, since no sign of suffering or stress could be detected. The efficacy of morphine on VB neuronal responses induced by mild stimulation of the joints was greatly reduced in morphine-pretreated arthritic rats, compared to naive animals (mean neuronal inhibition of 35 vs 85%, respectively). This indicates that the tolerance phenomena observed in behavioral studies are reflected at the VB level, on neurons involved in pain processes. In addition, naloxone (0.6, 1 and 2 mg/kg i.v.) induced a dramatic increase in the evoked (52, 88 and 93%) and spontaneous (64, 211 and 292%) VB neuronal activities recorded in morphine-pretreated arthritic rats, while these activities were not significantly altered in naive arthritic rats. The time-courses of the modifications induced by naloxone in morphine-pretreated arthritic animals were similar to those of the naloxone-precipitated morphine withdrawal observed in freely moving rats. These findings may represent the neuronal correlate at the VB level of the withdrawal response and/or the hyperalgesia induced in tolerant arthritic rats by high doses of naloxone.

Animals↗
PubMed1991

Behavioural evidence that systemic morphine may modulate a phasic pain-related behaviour in a rat model of peripheral mononeuropathy.

In a model of peripheral mononeuropathy produced by 4 ligatures around the sciatic nerve, we investigated the effects of various i.v. doses of morphine on the vocalization thresholds elicited by paw pressure and compared the effects obtained with the same doses in normal rats. In neuropathic rats, morphine (0.1 and 0.3 mg/kg) produced a significant analgesic effect on the lesioned hind paw, maximum at 15 min post injection with a recovery at 20-25 min. For doses of 0.6 and 1 mg/kg, a modification of the kinetics was observed, with maximum effect at 20-30 min post injection and a recovery at 50-80 min. An analgesic effect was also observed on the unlesioned side, significantly less potent than that observed on the lesioned paw. The effect of 1 mg/kg morphine was almost totally reversed by a 0.1 mg/kg dose of systemic naloxone. The effects induced by the successive doses of morphine on the lesioned paw appeared higher than in normal rats (maximum vocalization thresholds (% of control) following 1 mg/kg morphine (N = 12) were 193.92 +/- 6.57% versus 154 +/- 3.5% in normal rats N = 3), whereas they were comparable to those obtained from the sham-operated paw. The present data clearly show that morphine induces potent antinociceptive effects in a rat model of neuropathy, which seems to contradict the classical view that neuropathic pain is opioid resistant. Some possible pathophysiological mechanisms are discussed.

Animals↗
PubMed1990

The bidirectional dose-dependent effect of systemic naloxone is also related to the intensity and duration of pain-related disorders: a study in a rat model of peripheral mononeuropathy.

In an experimental model of mononeuropathy in the rat, created by 4 ligatures around the sciatic nerve, i.v. naloxone 1 week after surgery induces bidirectional effects (antinociceptive effects at very low doses, hyperalgesic effects with high doses). Using the same nociceptive test (vocalization thresholds to paw pressure), the activity of the same doses of naloxone (3 micrograms/kg, and 1 mg/kg) was investigated 2 weeks after sciatic ligation, when the behavioural pain-related disorders are at a maximum. Three micrograms/kg naloxone produced a significant antinociceptive effect on the lesioned and non-lesioned paw, which was clearly related to the degree as well as to the duration of pain-related signs in the rat. By contrast, the high dose of naloxone did not induce a mean significant effect when tested on either paw; however, it elicited a potent hyperalgesic effect in those rats which had recovered from hyperalgesia at this 2 week time point after the sciatic injury.

Animals↗
PubMed1990

Further evidence for 'pain-related' behaviours in a model of unilateral peripheral mononeuropathy.

A model of experimental peripheral neuropathy producing pain-related disorders has recently been described in the rat. The present study aimed to investigate, using a different and quantifiable behavioural approach, the abnormal pain-related sensations in the animals. The neuropathy was produced by 4 ligatures tied loosely around the common sciatic nerve. 6-8 days after surgery, most of the rats exhibited pain-related disorders ipsilateral to the sciatic ligation, which became maximal 2 weeks after surgery. Mechanical noxious stimulation (pinching of the hind paw) revealed hyperalgesia in all the animals. Rats also exhibited allodynia when tested with the vocalization threshold test to paw pressure (mean vocalization thresholds were 65.5 +/- 3.6% of the preoperative control, P less than 0.01, n = 95). Tests using heat (40, 42, 44, 46 degrees C) and cold (10 degrees C) stimulation (immersion of the rat's hind paw in a bath until it was observed to struggle) indicated hyperalgesia to noxious heat (decrease of 30% in the immersion duration (ID) at a temperature of 46 degrees C), and allodynia to non-noxious heat (decrease of 30% in the temperature of the struggle threshold) and to cold stimulation (decrease by 40% in the ID). In addition, the animals showed modifications in the spontaneous postures of the affected hind paw in a natural setting, suggesting a 'spontaneous' pain-related behaviour (the mean 'pain' rating, derived from the technique used for the formalin test and numbered 0-5, was 2.8 +/- 0.4, P less than 0.01, n = 12). Lastly, sensitized responses were observed to mechanical stimulation after thermal stimulation in the non-noxious range applied to the lesioned but not the non-lesioned paw. The time course of pain-related disorders was comparable whatever the behavioural test, with recovery 2 months after surgery. These results clearly show that the neuropathy produces abnormal pain-related disorders in the rat, which are reminiscent of those observed in some human neuropathies.

Animals↗
PubMed1989

Behavioural evidence for a bidirectional effect of systemic naloxone in a model of experimental neuropathy in the rat.

In animal models of inflammatory pain, we have demonstrated that the opioid antagonist naloxone induces a paradoxical analgesic effect at very low systemic doses, and a hyperalgesic effect at high doses. We have therefore proposed, that opioid systems are modified in these animals with persistent pain. The aim of the present study was to investigate the activity of naloxone through another model of pain in the rat due to a peripheral neuropathy of the sciatic nerve. The neuropathy was created by 4 ligatures around the sciatic nerve. We analyzed the effects of i.v. naloxone (3 and 10 micrograms/kg, 1 mg/kg) on the vocalization thresholds to paw pressure 8 days after the sciatic ligation. Three and 10 micrograms/kg naloxone produced a significant paradoxical antinociceptive effect on responses from the affected paw (with a mean increase of about 50 and 30% of the preinjection values, respectively) and also from the non-affected paw, although the effect was less potent. By contrast, 1 mg/kg naloxone elicited a significant hyperalgesia on responses from the affected and non-affected paw. The effects of the microdoses, but not those of the high dose, were clearly related to the vocalization thresholds measured for each rat just before injection. This study clearly shows that naloxone induces bidirectional effects in a rat model of neuropathic pain, which contradicts the current statement that neuropathic pain is opioid-resistant. The present results also suggest that these effects are not related to inflammatory processes, and may be due to modifications of opioid systems in these animals with persistent pain.

Animals↗