Papers by Rafael Benoliel
Oral Surgery, Oral Medicine, Oral Pathology, 1986
Oral Surgery, Oral Medicine, Oral Pathology, 1986
A probabilistic model analyzes the American Heart Association's (AHA) recommendations for the pre... more A probabilistic model analyzes the American Heart Association's (AHA) recommendations for the prevention of infective endocarditis (IE) of dental origin. The model, presented in the form of a flow chart, combines available data elements with the AHA recommendations; mortality serves as the sole valued outcome and payoff measure. The analysis shows that an annual death rate of 1.36 per million population is attributable to the antibiotics administered in an attempt to prevent IE, whereas not more than 0.26 annual deaths per million are traceable to IE of dental origin. Sensitivity and threshold analyses were conducted to determine the conditions under which the recommended prophylactic policy will prove beneficial. The model suggests that the standard AHA antibiotic regimen should be exploited only in IE susceptible patients belonging to the high risk categories and that its value in moderate, low, and negligible risk patients is doubtful. When the use of antibiotics is unavoidable, oral administration is the preferable route.
Journal of Clinical Periodontology, 1988
Abstract A case of Lichen Planus (LP) following periodontal surgery in a patient previously free ... more Abstract A case of Lichen Planus (LP) following periodontal surgery in a patient previously free of the disease is described. Genetic predisposition and lymphokine secretion stimulated by local trauma are suggested as a possible mechanism of the phenomenon. It is recommended that LP patients, especially those suffering from the erosive type, should be treated as conservatively as possible, minimizing the possibility of trauma to the oral tissues where local immunity may have been altered by a pathological process.
Journal of Clinical Periodontology, 1988
Abstract The peripheral blood lymphocyte subsets of 10 patients with rapidly progressive periodon... more Abstract The peripheral blood lymphocyte subsets of 10 patients with rapidly progressive periodontitis were investigated with monoclonal antibody. In 4 patients, the T helper/T suppressor ratio was increased. 5 others had a slightly reduced T helper/T suppressor ratio as compared to control group. These findings may indicate a possible cellular immune response in the pathogenesis of rapidly progressive periodontitis.
Oral Surgery, Oral Medicine, Oral Pathology, 1987
Oral Surgery, Oral Medicine, Oral Pathology, 1986
Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontology, 2005
Pain, 2002
The aim of the present study was to test the behavioural effect of infraorbital (IO) chronic cons... more 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.
Pain, 1999
Substance P (SP) plays a central role in the transduction of second messenger signals from primar... more Substance P (SP) plays a central role in the transduction of second messenger signals from primary afferent nociceptive terminals to second-order neurons in the spinal cord. We have tested a recombinant engineered diphtheria toxin/SP fusion protein (DAB389SP) in acute and chronic pain models in the rat. DAB389SP binds to the SP receptor (SPR) and is internalized and kills SPR-expressing cells by blocking cellular protein synthesis. DAB389SP delivery was by intrathecal infusion, of varying duration, at the lumbar level. In the chronic constriction injury model of neuropathic pain a significant reduction in mechanically induced hyperalgesia was obtained. This effect was less marked in an acute carageenan inflammation model. Although other pain characteristics (mechano-allodynia, cold-allodynia, and heathyperalgesia) showed some improvement, these were less pronounced. Immunocytochemistry revealed a toxin-induced reduction in lamina I, of SPR and of NMDA NR1 subunit receptor expressing neurons, and of c-Fos, an inducible molecular marker of persistent nociceptive activity. The use of cytotoxic fusion proteins to target specific cell types may be of considerable benefit in the study of nociception and the treatment of chronic pain.
Neuroscience Letters, 2001
Inflammation along a nerve trunk with no frank axonal nerve damage produced by complete Freund's ... more Inflammation along a nerve trunk with no frank axonal nerve damage produced by complete Freund's adjuvant (CFA) or Carrageenan is known to induce a painful peripheral neuropathy. In the present study, we examined the electrophysiological properties of myelinated axons (spontaneous discharge and mechanical sensitivity) at the inflamed nerve site. The rat saphenous nerves were exposed at mid-thigh level and wrapped in 2 mm wide bands of haemostatic oxidized cellulose (Oxycel®) that were saturated with undiluted CFA. In the control rats the Oxycel® was saturated with saline. At postoperative days (PODs) 2–5 and 6–10, fine axon bundles were teased from the nerve, and electrophysiological recordings performed. At both time points spontaneous activity at the site of the application in CFA rats (PODs 2–5=9.9±2.5%: PODs 6–10=6.1±1.4%) was significantly higher than in the control animals (PODs 2–5=2.9±1.1%: PODs 6–10=1.6±1.4%: P=0.03, P=0.02, respectively). Mechanical sensitivity at both time points was significantly higher in CFA rats (PODs 2–5=12.6±3.1%: PODs 6–10=10.3±3.1%) than in saline rats (PODs 2–5=3.4±2.91%: PODs 6–10=0.8±1.0%: P=0.03, P=0.04, respectively). This study clearly shows that perineural inflammation with no axonal nerve damage induced by CFA application around the nerve trunk elevates spontaneous activity and induces mechanosensitivity in myelinated axons.
Neuroscience Letters, 2001
Following sciatic nerve injury sympathetic invasion and basket formation is seen in dorsal root g... more Following sciatic nerve injury sympathetic invasion and basket formation is seen in dorsal root ganglia. We examined whether this phenomenon occurs in trigeminal ganglion (TG) following axotomy (IOA x ) or chronic constriction injury to the infraorbital nerve (IOCCI). The IOCCI rats developed hyperresponsiveness to pinprick stimulation consistent with this model and the IOAx rats remained hyporesponsive for most of the study period. Immunocytochemistry employing antibodies to tyrosine hydroxylase showed no sympathetic invasion or basket formation 2 and 7 weeks post surgery. This study con®rms previous work that found no sympathetic invasion of TG following injury, and shows that this ®nding is unaffected by the presence or absence of nerve injury induced hyperresponsiveness. q 2001 Published by Elsevier Science Ireland Ltd.
Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontology, 2007
Current management of painful trigeminal neuropathies relies on pharmacological (topical and syst... more Current management of painful trigeminal neuropathies relies on pharmacological (topical and systemic), surgical, and complementary modalities. There is, however, a lack of quality research relating to the effectiveness of these modalities. In this review we analyze the available data that relates to the therapy of trigeminal neuralgia, postherpetic neuralgia, and posttraumatic neuropathies and provide clinical guidelines. The review focuses on medical management, as well as surgical and other interventions for painful neuropathies. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103(suppl 1):S32.e1-S32.e24)
Neuroscience Letters, 2000
Glutamate, substance P (SP), and their receptors have been implicated in the initiation and maint... more Glutamate, substance P (SP), and their receptors have been implicated in the initiation and maintenance of persistent pain through an interaction at second order spinal cord neurons. Employing well-characterized antibodies to the SP receptor and the N-methyl-d-aspartate receptor (NR1 subunit, splice variant missing exon 22), we demonstrate colocalization of these receptors on second order neurons at cervical, thoracic, lumbar, and sacral spinal cord levels. The co-localization was marked in lamina I of the dorsal horn at all levels and in the intermediolateral nucleus of the thoraco-lumbar spinal cord nuclei associated with autonomic function. q
Oral and Maxillofacial Surgery Clinics of North America, 2008
Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontology, 2008
Objectives. The objective of this study was to analyze the etiological factors and neurosensory s... more Objectives. The objective of this study was to analyze the etiological factors and neurosensory signatures of patients attending with a primary complaint of numb chin. Methods. Charts of 27 patients referred to Hadassah School of Dental Medicine, Jerusalem, Israel, with a complaint of unilateral numbness or paresthesias of the chin were reviewed. Demographic and etiologic data and special tests, including imaging, that were prescribed as necessary for the treatment protocol were evaluated. The neurosensory evaluation protocol included assessment of detection thresholds to electrical stimulation (assessing large myelinated nerve fibers) and heat (assessing thin unmyelinated nerve fibers) in the mental and infraorbital nerves regions bilaterally. Data from 8 healthy, age and sex-matched subjects who underwent similar sensory testing served as the control group. Results. Invasive dental procedures (eg, extractions, implants) were the etiologic factor in 63% of the cases. Inflammatory pathoses (15%) (eg, periapical periodontitis or infection), and malignant lesions (22%) were identified as causative in the remaining patients. Frank nerve injury due to advanced malignant processes was characterized by significantly elevated heat and electrical thresholds (hyposensitivity). Inflammatory process was accompanied by reduced electrical detection thresholds (hypersensitivity). Conclusions. This study concurs with previous studies that sensory hyposensitivity accompanies nerve damage. Accordingly, quantitative sensory testing may contribute to the diagnostic process of patients with mental nerve neuropathy. In this sample of patients, the most common cause for mental nerve neuropathy was dental treatment followed by malignant metastasis.
Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontology, 1997
To examine whether a classifiable primary vascular-type craniofacial pain subgroup exists that pr... more To examine whether a classifiable primary vascular-type craniofacial pain subgroup exists that predominantly affects intraoral structures. Fifty-five patients were chosen prospectively according to the following inclusion criteria; periodic craniofacial pain that was unilateral, pulsatile, severe, and that may wake the patient from sleep. Accompanying phenomena could include local autonomic and/or systemic signs. Twenty-six cases could be further classified into one of the categories of vascular craniofacial pain. The remaining 29, all with predominantly intraoral pain, were not readily classifiable. Of the 29 patients 70% were women, with an average onset-age of 42.6 years. All reported severe, episodic pain that was usually unilateral and lasted minutes to hours. In all, 55% of patients had autonomic or systemic signs, 48% had pulsatile pain, and 35.4% of patients were awakened by the pain. Although clinical similarities were observed within these patients, further studies are needed to confirm vascular orofacial pain as a clear diagnostic category.
Journal of Dental Research, 2007
The mechanisms involved, and possible treatment targets, in orofacial pain due to cancer are poor... more The mechanisms involved, and possible treatment targets, in orofacial pain due to cancer are poorly understood. The aim of the first of this two-part series is to review the involved pathophysiological mechanisms and explore their possible roles in the orofacial region. However, there is a lack of relevant research in the trigeminal region, and we have therefore applied data accumulated from experiments on cancer pain mechanisms in rodent spinal models. In the second part, we review the clinical presentation of cancer-associated orofacial pain at various stages: initial diagnosis, during therapy (chemo-, radiotherapy, surgery), and in the post-therapy period. In the present article, we provide a brief outline of trigeminal functional neuro-anatomy and pain-modulatory pathways. Tissue destruction by invasive tumors (or metastases) induces inflammation and nerve damage, with attendant acute pain. In some cases, chronic pain, involving inflammatory and neuropathic mechanisms, may ensue. Distant, painful effects of tumors include paraneoplastic neuropathic syndromes and effects secondary to the release of factors by the tumor (growth factors, cytokines, and enzymes). Additionally, pain is frequent in cancer management protocols (surgery, chemotherapy, and radiotherapy). Understanding the mechanisms involved in cancer-related orofacial pain will enhance patient management.
Pain, 2002
The present experiments investigated the behavioral and immunocytchemical (ICC) effects of applyi... more 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.
Pain, 2001
The aim of this study was to investigate neuropeptide Y (NPY) levels in trigeminal ganglia follow... more The aim of this study was to investigate neuropeptide Y (NPY) levels in trigeminal ganglia following infraorbital nerve injury. Two experimental procedures were performed in three groups of rats: a unilateral chronic constriction injury (CCI) to the infraorbital nerve (n 13), nerve manipulation without CCI (n 13) and unoperated controls (n 8). All rats underwent baseline and regular assessment of mechanical withdrawal threshold (Von Frey) and reaction to pin prick as well as free behavior evaluations. CCI to the infraorbital nerve induced signi®cant hyperalgesia and allodynia within 9±12 days. At 6 days seven rats were euthanized and trigeminal ganglia harvested for immunocytochemical (ICC) studies. The study was ended at 14 days when all rats were euthanized and their ganglia harvested for ICC and radioimmunoassay (RIA) studies. An increase in NPY levels was seen in the ipsilateral ganglia of manipulated and CCI rats at 6 days, when rats displayed no pain-related behavior. At 14 days, ICC and RIA both detected signi®cant increases in NPY levels in the ipsilateral ganglia of CCI and manipulated rats but not in unoperated controls. The possible roles of NPY in pain modulation and nerve injury are discussed in light of these ®ndings.
Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontology, 2005
Objective. To document the neurosensory changes in the infraorbital nerve following zygomatic fra... more Objective. To document the neurosensory changes in the infraorbital nerve following zygomatic fractures managed in various ways.
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Papers by Rafael Benoliel