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Biomedical subjects

Rafael Benoliel

Publications and source records attributed to Rafael Benoliel.

11 recordsLinked to original sources

Effects of topiramate on the chronic constriction injury model in the rat.

UNLABELLED: We studied the effects of topiramate at a relatively low dose of 20 mg/kg/d in rats that underwent chronic constriction injury (CCI) to the sciatic nerve. Fourteen rats underwent CCI and were then divided into two groups: one treated with topiramate and the other with an equal volume of saline. A further group of six rats was sham operated and treated with topiramate. Rats were examined over a period of 13 days for the presence of mechanoallodynia (von Frey hairs) and mechanohyperalgesia (pinprick test) and then euthanized and the degree of nerve injury was assessed by measuring the expression of neuropeptide Y (NPY) in dorsal root ganglia with enzyme-linked immunosorbent assay. Topiramate, at a lower dose than previously reported, significantly delayed the onset of allodynia and both delayed and attenuated the peak hyperalgesia observed. NPY levels were not significantly different between the operated groups. PERSPECTIVE: Topiramate is employed in various pain conditions and this study suggests that lower doses may be effective in neuropathic pain. Clinically this may mean reduced side effects. Additionally the potential of topiramate as a neuroprotectant is studied and, although the results were negative, this area needs further research.

Analysis of Variance↗

Trigeminal neurosensory changes following acute and chronic paranasal sinusitis.

OBJECTIVE: The aim of this study was to document sensory changes in the supraorbital, infraorbital, and mental nerve distributions following acute and chronic maxillary and frontal sinusitis. METHOD AND MATERIALS: Seven patients with a total of 14 infected sinuses were included in the study. Neurosensory function was evaluated by measuring the electrical detection threshold for large myelinated nerve fibers and heat detection thresholds for the assessment of the thin unmyelinated nerve fibers. The sensory tests were conducted in the infraorbital, supraorbital, and mental dermatomes. Patient evaluation included clinical examination and computerized tomographic imaging of the sinuses. Sinusitis symptoms of 1 month or less were considered acute, and symptoms that persisted for more than 3 months were considered chronic. Detection thresholds in 8 healthy volunteers served as controls. RESULTS: Eight acute and 6 chronic sinusitis cases were diagnosed. Acute sinusitis produced bilateral large myelinated fiber hypersensitivity (electrical) relative to healthy controls, with no significant change in the thin unmyelinated nerve fiber detection threshold (thermal). Chronic sinusitis resulted in large myelinated fiber hyposensitivity and thin myelinated fiber bilateral hyposensitivity, as compared to healthy controls. CONCLUSIONS: This study concurs with previous studies in finding that early inflammatory neuritis can produce large myelinated nerve fiber hypersensitivity, while long-lasting processes, presumably accompanied with early nerve damage, may result in hyposensitivity.

Acute Disease↗

Neurosensory changes in the infraorbital nerve following zygomatic fractures.

OBJECTIVE: To document the neurosensory changes in the infraorbital nerve following zygomatic fractures managed in various ways. STUDY DESIGN: Twenty-five patients were included in the study. Neurosensory function was assessed with calibrated nylon monofilaments, electrical stimulation, heat detection thresholds and response to pin prick in the infraorbital, supraorbital, and mental nerve regions. Patients were seen immediately post-trauma, then 1 and 6 months following surgery. RESULTS: Nine fractures were caused by traffic accidents (TAs), 8 by falls, and 8 by a local blow in a physical dispute. The fractures consisted of 15 displaced and 10 minimally or nondisplaced zygomatic complex fractures, and were left surgically untreated in 7 cases (None group), reduced but not fixed in 8 cases (Reduction group), and fixed with plates in 10 cases (Plates group). Plates were employed significantly more often in displaced fractures (chi-squared P = .0006). At 6 months significantly improved infraorbital nerve function was found in the Plate and None groups relative to the Reduction group (ANOVA P = .006). Only 1 case of chronic neuropathic pain was found. CONCLUSIONS: This study concurs with previous studies in finding that plate fixation allows for significantly better restoration of infraorbital nerve function. Chronic neuropathic pain following zygomatic fractures is rare.

Adolescent↗

Experimental malignancy in the rat induces early hypersensitivity indicative of neuritis.

Cancer pain mechanisms involve multiple factors including the accompanying inflammatory process neural effects. Inflammation along a nerve trunk (neuritis) has been shown to induce hypersensitivity at the innervated target organ. In this experiment the neural effects of MAT B mammary adenocarcinoma cells implanted adjacent to sciatic nerve (MAT group) were compared to those induced by thymus cell extract (THY), saline (SAL) and the potent proinflammatory agent Complete Freund's adjuvant (CFA). Significant pain behavior was detected only in the ipsilateral hindpaw of MAT and CFA rats lasting seven days post-operatively (dpo). On the ninth dpo MAT rats developed significant hyposensitivity to mechanical and electrical stimuli. Interleukin (IL)-6 levels (ELISA) from MAT and CFA exposed nerves were significantly elevated at dpo 2 and remained so in MAT at dpo 8. Indomethacin (1 mg/kg i.p.) abolished the observed pain responses in MAT and CFA rats exposed nerves. Light microscopy of the MAT nerves at the second dpo revealed neural infiltration of immune and malignant cells with mild edema. By the seventh dpo there was nerve damage and at dpo 14 nerve tissue was largely replaced by malignant and immune cells. Electrophysiology of saphenous nerves exposed to MAT, CFA or SAL revealed significantly increased spontaneous activity in MAT and CFA groups. Spike response to hindpaw mechanical stimulation was significantly reduced only in the MAT group (dpo 6-9) suggestive of nerve damage. Inflammatory neuritis is an early expression of malignancy and may play a role in chronic cancer-related pain initiation and additionally may offer diagnostic opportunities.

Action Potentials↗

Quantitative sensory testing in trigeminal nerve damage assessment.

Evaluating sensory nerve damage is a challenging and often frustrating process. Diagnosis and follow-up is usually based on the patient's history and gross physical evaluation in addition to simple sensory tests such as brushing or pin prick. Based on evidence accumulated from clinical and animal experiments, quantitative sensory testing (QST) has emerged as a useful tool in the assessment of sensory nerve damage. QST has demonstrated diagnostic capabilities in temporomandibular disorders, burning mouth syndrome, oral malignancies, numb chin syndrome, posttraumatic pain, and whiplash injuries, and in elucidating mechanisms of central sensitization. In this article specific clinical uses of QST are described and its clinical applicability is demonstrated. Future studies should be directed at exploring the use of QST in the diagnosis and classification of further nerve pathologies.

Burning Mouth Syndrome↗

Facial arthralgia and myalgia: can they be differentiated by trigeminal sensory assessment?

Heat and electrical detection thresholds were assessed in 72 patients suffering from painful temporomandibular disorder. Employing widely accepted criteria, 44 patients were classified as suffering from temporomandibular joint (TMJ) arthralgia (i.e. pain originating from the TMJ) and 28 from myalgia (i.e. pain originating from the muscles of mastication). Electrical stimulation was employed to assess thresholds in large myelinated nerve fibers (Abeta) and heat application to assess thresholds in unmyelinated nerve fibers (C). The sensory tests were performed bilaterally in three trigeminal nerve sites: the auriculotemporal nerve territory (AUT), buccal nerve territory (BUC) and the mental nerve territory (MNT). In addition, 22 healthy asymptomatic controls were examined. A subset of ten arthralgia patients underwent arthrocentesis and electrical detection thresholds were additionally assessed following the procedure. Electrical detection threshold ratios were calculated by dividing the affected side by the control side, thus reduced ratios indicate hypersensitivity of the affected side. In control patients, ratios obtained at all sites did not vary significantly from the expected value of 'one' (mean with 95% confidence intervals; AUT, 1:0.95-1.06; BUC, 1.01:0.93-1.11; MNT, 0.97:0.88-1.05, all areas one sample analysis P>0.05). In arthralgia patients mean ratios (+/-SEM) obtained for the AUT territory (0.63+/-0.03) were significantly lower compared to ratios for the MNT (1.02+/-0.03) and BUC (0.96+/-0.04) territories (repeated measures analysis of variance (RANOVA), P<0.0001) and compared to the AUT ratios in myalgia (1.27+/-0.09) and control subjects (1+/-0.06, ANOVA, P<0.0001). In the myalgia group the electrical detection threshold ratios in the AUT territory were significantly elevated compared to the AUT ratios in control subjects (Dunnett test, P<0.05), but only approached statistical significance compared to the MNT (1.07+/-0.04) and BUC (1.11+/-0.06) territories (RANOVA, F(2,27)=3.12, P=0.052). There were no significant differences between and within the groups for electrical detection threshold ratios in the BUC and MNT nerve territories, and for the heat detection thresholds in all tested sites. Following arthrocentesis, mean electrical detection threshold ratios in the AUT territory were significantly elevated from 0.64+/-0.06 to 0.99+/-0.04 indicating resolution of the hypersensitivity (paired t-test, P=0.001). In conclusion, large myelinated fiber hypersensitivity is found in the skin overlying TMJs with clinical pain and pathology but is not found in controls. In patients with muscle-related facial pain there was significant elevation of the electrical detection threshold in the AUT region.

Adult↗

Management of chronic orofacial pain: today and tomorrow.

In the facial region, chronic pain syndromes include musculoskeletal pain, neuropathic disorders, vascular pain, and other chronic headaches. Therapy of chronic facial pain syndromes often relies on long-term psychotropic medications that cause severe side effects and offer nontotal pain relief. In this article, therapeutically relevant advances in science, which will change the approach to pain management, are reviewed. Understanding the mechanisms involved in chronic pain enables the clinician to skillfully apply this knowledge when selecting a therapy.

Afferent Pathways↗

Strain-dependent modification of neuropathic pain behaviour in the rat hindpaw by a priming painful trigeminal nerve injury.

The aim of the present study was to test the behavioural effect of infraorbital (IO) chronic constriction injury (CCI) on the development of neuropathic pain in the rat hindpaw following sciatic nerve CCI performed 7 days later. Control groups consisted of rats that underwent sham infraorbital surgery followed by sciatic CCI at identical time points. Sensory testing of the rat's face and hindpaw was performed at baseline and at 4, 11, 14, 17 and 21 days postoperative (dpo) relative to the IOCCI, at which time all rats were euthanized. To test for strain differences the experiment was performed on Sprague-Dawley, Sabra and Lewis rats. In Lewis rats the trigeminal nerve injury significantly accelerated the development of hindpaw mechanoallodynia (11th, 14th and 17th dpo, unpaired t-test, P<0.05) and mechanohyperalgesia (14th and 17th dpo, unpaired t-test, P<0.05), following a second sciatic nerve CCI relative to the control group. This effect was not observed in Sprague-Dawley or Sabra rats.

Animals↗

Application of a pro-inflammatory agent to the orbital portion of the rat infraorbital nerve induces changes indicative of ongoing trigeminal pain.

The present experiments investigated the behavioral and immunocytchemical (ICC) effects of applying complete Freund's adjuvant (CFA) to the orbital portion of the infraorbital nerve (IOn). Two control groups, the first had saline applied to the IOn and the second underwent sham operation, were included in the study. In the CFA group, significant hyper-responsiveness to von Frey (analysis of variance <0.05) and to pinprick stimulation (Kruskal Wallis <0.05) in the vibrissal pad was observed on the fourth and the fifth days post-operative (dpo). This was accompanied by a reduced bite force and altered bite patterns of similar duration. Histology of the IOn in CFA rats revealed immune cell infiltration and edema around and in the nerve trunk with only mild axonal damage confirmed by neuropeptide Y immunoreactivity in trigeminal ganglion. Histological areas of inconsistent and mild inflammation were observed in the saline group that were accompanied by similarly attenuated behavioral and ICC changes. This model of inflammation-induced neuropathic pain is highly applicable to the study of neuroinflammatory orofacial pain.

Animals↗

Large myelinated nerve fiber hypersensitivity in oral malignancy.

OBJECTIVES: The purpose of this study was to assess the sensory function of trigeminal nerve A-beta fibers in suspected soft tissue oral malignancies. STUDY DESIGN: Twenty-three patients referred for the evaluation of an oral lesion suspected of malignancy were included in the study. All lesions were classified as in, near, or out of the nerve territory containing the lesion. Within these subgroups we assessed the sensitivity of A-beta primary afferents to weak electrical currents applied bilaterally to regions innervated by 3 peripheral branches of the trigeminal nerve. The ratio of electrical detection thresholds from the affected and the unaffected side was calculated. Electrical detection threshold ratios were contrasted with the results of physical examination, radiographic imaging, and biopsy. RESULTS: For dermatomes containing the lesions, ratios were lower than 0.8 in 12 patients. Biopsy showed that the lesions in 10 of these 12 patients were malignant. No malignancy was found in the remaining 11 patients. CONCLUSIONS: A-beta primary afferent hypersensitivity is observed to occur in nerves exposed to soft tissue oral malignancy.

Adult↗

Hemicrania continua.

Unilateral throbbing headaches may present similar signs and symptoms as dental pathology and are a diagnostic challenge for dental practitioners. Cases may be seen with a primary complaint of unilateral pain or referred by medical colleagues for exclusion of dental causes. In the present article the authors add a new case of hemicrania continua (HC), which is one such unilateral headache, and review the previously published cases. HC is relatively easy to treat since it responds completely to treatment with indomethacin. However, as is presented in this case, HC may masquerade as dental pain. Cases secondary to trauma, systemic disease, and nervous system pathology have been described in the literature, and the clinician must exclude these possible causes. A thorough knowledge of this entity is therefore essential.

Adult↗