Non-invasive measurement of trigeminal nerve somatosensory evoked potentials

Whiplash injuries are common yet enigmatic to substantiate clinically. Trigeminal somatosensory evoked potentials (TSEPs) were posited as an indicator of trigeminal nerve conduction damage resulting from whiplash. Alternating polarity square-wave current stimuli were applied transcutaneously in the facial region. 379 recorded pilot trials from 27 participants (8 male and 19 female) were utilized to develop a non-invasive recording capability for TSEPs. Stimulus intensity and artifact, cortical recording sites, stimulation electrode design and placement were explored. Statistically significant differences in amplitude of TSEP waveform components at 13, 19 and 27 ms between uninjured and whiplashed participants were noted. Increased stimulus intensity in whiplashed participants was observed to increase TSEP amplitude. The present methodology and hardware are discussed and directions for future advancement of the current process are outlined.

Nerve Growth Factor Sensitisation of TRPA1 on Sensory Neurones

Background: Sensory neurones from the trigeminal nerve innervate the oro-facial region and teeth. Transient receptor potential channels (TRPs) expressed by these neurones are responsible for relaying sensory information such as changes in ambient temperature, mechanical sensations and pain. Study of TRP channel expression and regulation in human sensory neurones therefore merits investigation to improve our understanding of allodynia and hyperalgesia. Objective: The objective of this study was to differentiate human dental pulp stem cells (hDPSCs) towards a neuronal phenotype (peripheral neuronal equivalents; PNEs) and employ this model to study TRP channel sensitisation. Method: hDPSCs were enriched by preferential adhesion to fibronectin, plated on coverslips (thickness 0) coated with poly-l-ornithine and laminin and then differentiated for 7 days in neurobasal A medium with additional supplementation. A whole cell patch clamp technique was used to investigate whether TRP channels on PNE membranes were modulated in the presence of nerve growth factor (NGF). PNEs were treated with NGF for 20 minutes immediately before experimentation and then stimulated for TRPA1 activity using cinnamaldehyde. Peak currents were read at 80 mV and -80 mV and compared to peak currents recorded in untreated PNEs. Data were analysed and plotted using Clampfit9 software (Molecular Devices, Sunnyvale, California, USA). Result: Results showed for the first time that pre-treatment of PNEs by NGF produced significantly larger inward and outward currents demonstrating that TRPA1 channels on PNE membranes were capable of becoming sensitised following treatment with NGF. Conclusion: Sensitisation of TRPA1 by NGF provides evidence of a mechanism for rapid neuronal sensitisation that is independent of TRPA1 gene expression

An in vitro model of nociceptors in human trigeminal nerves

Background: The oro-facial region is densely innervated by the trigeminal nerve, which when stimulated can induce noxious pain sensation and contribute to neurogenic inflammation in local tissues. Recent research on the expression of specialised ion channels on the trigeminal nerve has highlighted the need to undertake more extensive studies on ion channel expression/functionality with the aim of elucidating their role in pain sensations. A major family of such ion channels is the transient receptor potential (TRP) channels which are activated by a wide variety of thermal, mechanical or chemical stimuli and merit investigation as possible druggable targets for future analgesics.
Objective: Study of TRP channel expression and regulation in oro-facial tissues is hindered by the fact that the cell bodies of neurons innervating these tissues are located in the trigeminal ganglion. Using dental pulp stem cells differentiated towards peripheral neuronal equivalents (PNEs), we sought to determine TRP channel expression, functionality and potential modulation by cytokines in this novel model.
Method: Dental pulp stem cells (DPSCs) were grown on substrate-coated tissue culture plates and differentiated towards a neuronal phenotype using neuronal induction media. Quantitative polymerase chain reaction (qPCR) was performed on PNEs +/-cytokine treatment. Ion channel functionality was investigated using whole cell patch clamping.
Result: qPCR analysis showed that PNEs expressed the TRP channels TRPA1, TRPV1, TRPV4 and TRPM8. TRPA1 was the most abundantly expressed TRP channel studied whereas TRPM8 was lowly expressed. TRP channel expression was shown to be regulated by treatment with inflammatory cytokines. Patch clamp studies using specific agonists and antagonists for TRPA1 and TRPV1 showed these channels were functional.
Conclusion: PNEs differentiated from DPSCs provide a suitable model for TRP channel expression, regulation, and sensistisation in oro-facial tissues. This human neuronal model has potential for use in pre-clinical studies of novel analgesics.

Trigeminal neuralgia: Literature review

The trigeminal nerve, fifth equal of cranial nerves, a mixed nerve is considered by possessing motor and sensitive components. The sensitive portion takes to the Nervous System Central somesthesics information from the skin and mucous membrane of great area of the face, being responsible also for a neural disease, known as the Trigeminal Neuralgia. The aim of this study was to review the literature on the main characteristics of Trigeminal Neuralgia, the relevant aspects for the diagnosis and treatment options for this pathology. This neuralgia is characterized by hard pains and sudden, similar to electric discharges, with duration between a few seconds to two minutes, in the trigeminal nerve sensorial distribution. The pain is unchained by light touches in specific points in the skin of the face or for movements of the facial muscles, it can be caused by traumatic sequels or physiologic processes degenerative associate the vascular compression. Prevails in the senior population, frequently in the woman. In a unilateral way it attacks more the maxillary and mandibular divisions, rarely happens in a simultaneous way in the three branches of trigeminal nerve three branches.

Microvascular decompression for trigeminal neuralgia in the elderly: long-term treatment outcome and comparison with younger patients

OBJECTIVE: Multiple studies have proved that microvascular decompression (MVD) is the treatment of choice in cases of medically refractory trigeminal neuralgia (TN). In the elderly, however, the surgical risks related to MVD are assumed to be unacceptably high and various alternative therapies have been proposed. We evaluated the outcomes of MVD in patients aged older than 65 years of age and compared them with the outcomes in a matched group of younger patients. The focus was on procedure-related morbidity rate and long-term outcome. METHODS: This was a retrospective study of 112 patients with TN operated on consecutively over 22 years. The main outcome measures were immediate and long-term postoperative pain relief and neurological status, especially function of trigeminal, facial, and cochlear nerves, as well as surgical complications. A questionnaire was used to assess long-term outcome: pain relief, duration of a pain-free period, need for pain medications, time to recurrence, pain severity, and need for additional treatment. RESULTS: The mean age was 70.35 years. The second and third branches of the trigeminal nerve were most frequently affected (37.3%). The mean follow-up period was 90 months (range, 48-295 months). Seventy-five percent of the patients were completely pain free, 11% were never pain free, and 14% experienced recurrences. No statistically significant differences existed in the outcome between the younger and older patient groups. Postoperative morbidity included trigeminal hypesthesia in 6.25%, hypacusis in 5.4%, and complete hearing loss, vertigo, and partial facial nerve palsy in 0.89% each. Cerebrospinal fluid leak and meningitis occurred in 1 patient each. There were no mortalities in both groups. CONCLUSION: MVD for TN is a safe procedure even in the elderly. The risk of serious morbidity or mortality is similar to that in younger patients. Furthermore, no significant differences in short- and long-term outcome were found. Thus, MVD is the treatment of choice in patients with medically refractory TN, unless their general condition prohibits it.

Investigation of lymphotoxin α genetic variants in migraine

Migraine is a common neurological disease with a genetic basis affecting approximately 12% of the population. Pain during a migraine attack is associated with activation of the trigeminal nerve system, which carries pain signals from the meninges and the blood vessels infusing the meninges to the trigeminal nucleus in the brain stem. The release of inflammatory mediators following cortical spreading depression (CSD) may further promote and sustain the activation and sensitization of meningeal nociceptors, inducing the persistent throbbing headache characterised in migraine. Lymphotoxin α (LTA) is a cytokine secreted by lymphocytes and is a member of the tumour necrosis factor (TNF) family. Genetic variation with the TNF and LTA genes may contribute to threshold brain excitability, propagation of neuronal hyperexcitability and thus initiation and maintenance of a migraine attack. Three LTA variants rs2009658, rs2844482 and rs2229094 were identified in a recent pGWAS study conducted in the Norfolk Island population as being potentially implicated in migraine with nominally significant p values of p = 0.0093, p = 0.0088 and p = 0.033 respectively. To determine whether these SNPs played a role in migraine in a general outbred population these SNPs were gentoyped in a large case control Australian Caucasian population and tested for association with migraine. All three SNPs showed no association in our cohort (p > 0.05). Validation of GWAS data in independent case-controls cohorts is essential to establish risk validity within specific population groups. The importance of cytokines in modulating neural inflammation and pain threshold in addition to other studies showing associations between TNF-α and SNPs in the LTA gene with migraine, suggests that LTA could be an important factor contributing to migraine. Although the present study did not support a role for the tested LTA variants in migraine, investigation of other variants within the LTA gene is still warranted.

Phagocytosis of bacteria by olfactory ensheathing cells and Schwann cells

Opportunistic bacterial infections of the nasal cavity could potentially lead to infection of the brain if the olfactory or trigeminal nerves are colonised. The olfactory nerve may be a more susceptible route because primary olfactory neurons are in direct contact with the external environment. Peripheral glia are known to be able to phagocytose some species of bacteria and may therefore provide a defence mechanism against bacterial infection. As the nasal cavity is frequently exposed to bacterial infections, we hypothesised that the olfactory and trigeminal nerves within the nasal cavity could be subjected to bacterial colonisation and that the olfactory ensheathing cells and Schwann cells may be involved in responding to the bacterial invasion. We have examined the ability of mouse OECs and Schwann cells from the trigeminal nerve and dorsal root ganglia to phagocytose Escherichia coli and Burkholderia thailandensis in vitro. We found that all three sources of glia were equally able to phagocytose E. coli with 75-85% of glia having phagocytosed bacteria within 24h. We also show that human OECs phagocytosed E. coli. In contrast, the mouse OECs and Schwann cells had little capacity to phagocytose B. thailandensis. Thus subtypes of peripheral glia have similar capacities for phagocytosis of bacteria but show selective capacity for the two different species of bacteria that were examined. These results have implications for the understanding of the mechanisms of bacterial infections as well as for the use of glia for neural repair therapies.

Stereotactic radiosurgery for intractable cluster headache: an initial report from the North American Gamma Knife Consortium.

Abstract Object The aim of this study was to evaluate the outcomes of Gamma Knife surgery (GKS) when used for patients with intractable cluster headache (CH). Methods Four participating centers of the North American Gamma Knife Consortium identified 17 patients who underwent GKS for intractable CH between 1996 and 2008. The median patient age was 47 years (range 26-83 years). The median duration of pain before GKS was 10 years (range 1.3-40 years). Seven patients underwent unsuccessful prior surgical procedures, including microvascular decompression (2 patients), microvascular decompression with glycerol rhizotomy (2 patients), deep brain stimulation (1 patient), trigeminal ganglion stimulation (1 patient), and prior GKS (1 patient). Fourteen patients had associated autonomic symptoms. The radiosurgical target was the trigeminal nerve (TN) root and the sphenopalatine ganglion (SPG) in 8 patients, only the TN in 8 patients, and only the SPG in 1 patient. The median maximum TN and SPG dose was 80 Gy. Results Favorable pain relief (Barrow Neurological Institute Grades I-IIIb) was achieved and maintained in 10 (59%) of 17 patients at a median follow-up of 34 months. Three patients required additional procedures (repeat GKS in 2 patients, hypothalamic deep brain stimulation in 1 patient). Eight (50%) of 16 patients who had their TN irradiated developed facial sensory dysfunction after GKS. Conclusions Gamma Knife surgery for intractable, medically refractory CH provided lasting pain reduction in approximately 60% of patients, but was associated with a significantly greater chance of facial sensory disturbances than GKS used for trigeminal neuralgia.

True navigation in migrating gulls requires intact olfactory nerves

During migratory journeys, birds may become displaced from their normal migratory route. Experimental evidence has shown that adult birds can correct for such displacements and return to their goal. However, the nature of the cues used by migratory birds to perform long distance navigation is still debated. In this experiment we subjected adult lesser black-backed gulls migrating from their Finnish/Russian breeding grounds (from >60°N) to Africa (to < 5°N) to sensory manipulation, to determine the sensory systems required for navigation. We translocated birds westward (1080 km) or eastward (885 km) to simulate natural navigational challenges. When translocated westwards and outside their migratory corridor birds with olfactory nerve section kept a clear directional preference (southerly) but were unable to compensate for the displacement, while intact birds and gulls with the ophthalmic branch of the trigeminal nerve sectioned oriented towards their population-specific migratory corridor. Thus, air-borne olfactory information seems to be important for migrating gulls to navigate successfully in some circumstances.

The immediate effects of atlanto-occipital joint manipulation and suboccipital muscle inhibition technique on active mouth opening and pressure pain sensitivity over latent myofascial trigger points in the masticatory muscles

DESIGN: A randomized controlled trial.OB JECTIVE: To investigate the immediate effects on pressure pain thresholds over latent trigger points (TrPs) in the masseter and temporalis muscles and active mouth opening following atlanto-occipital joint thrust manipulation or a soft tissue manual intervention targeted to the suboccipital muscles. BACKGROUND : Previous studies have described hypoalgesic effects of neck manipulative interventions over TrPs in the cervical musculature. There is a lack of studies analyzing these mechanisms over TrPs of muscles innervated by the trigeminal nerve. METHODS: One hundred twenty-two volunteers, 31 men and 91 women, between the ages of 18 and 30 years, with latent TrPs in the masseter muscle, were randomly divided into 3 groups: a manipulative group who received an atlanto-occipital joint thrust, a soft tissue group who received an inhibition technique over the suboccipital muscles, and a control group who did not receive an intervention. Pressure pain thresholds over latent TrPs in the masseter and temporalis muscles, and active mouth opening were assessed pretreatment and 2 minutes posttreatment by a blinded assessor. Mixed-model analyses of variance (ANOVA) were used to examine the effects of interventions on each outcome, with group as the between-subjects variable and time as the within-subjects variable. The primary analysis was the group-by-time interaction. RESULTS: The 2-by-3 mixed-model ANOVA revealed a significant group-by-time interaction for changes in pressure pain thresholds over masseter (P<.01) and temporalis (P =.003) muscle latent TrPs and also for active mouth opening (P<.001) in favor of the manipulative and soft tissue groups. Between-group effect sizes were small. CONCLUSIONS: The application of an atlanto-occipital thrust manipulation or soft tissue technique targeted to the suboccipital muscles led to an immediate increase in pressure pain thresholds over latent TrPs in the masseter and temporalis muscles and an increase in maximum active mouth opening. Nevertheless, the effects of both interventions were small and future studies are required to elucidate the clinical relevance of these changes. LEVEL OF EVIDENCE : Therapy, level 1b. J Orthop Sports Phys Ther 2010;40(5):310-317. doi:10.2519/jospt.2010.3257. KEYWORDSDS: cervical manipulation, muscle trigger points, neck, TMJ, upper cervical.

Les mécanismes synaptiques et intrinsèques qui sous-tendent l’activité des cellules réticulospinales (RS) en réponse à une stimulation sensorielle de type cutané chez la lamproie

Chez diverses espèces animales, les informations sensorielles peuvent déclencher la locomotion. Ceci nécessite l’intégration des informations sensorielles par le système nerveux central. Chez la lamproie, les réseaux locomoteurs spinaux sont activés et contrôlés par les cellules réticulospinales (RS), système descendant le plus important. Ces cellules reçoivent des informations variées provenant notamment de la périphérie. Une fois activées par une brève stimulation cutanée d’intensité suffisante, les cellules RS produisent des dépolarisations soutenues de durées variées impliquant des propriétés intrinsèques calcium-dépendantes et associées à l’induction de la nage de fuite. Au cours de ce doctorat, nous avons voulu savoir si les afférences synaptiques ont une influence sur la durée des dépolarisations soutenues et si l’ensemble des cellules RS partagent des propriétés d’intégration similaires, impliquant possiblement les réserves de calcium internes. Dans un premier temps, nous montrons pour la première fois qu’en plus de dépendre des propriétés intrinsèques des cellules réticulospinales, les dépolarisations soutenues dépendent des afférences excitatrices glutamatergiques, incluant les afférences spinales, pour perdurer pendant de longues périodes de temps. Les afférences cutanées ne participent pas au maintien des dépolarisations soutenues et les afférences inhibitrices glycinergique et GABAergiques ne sont pas suffisantes pour les arrêter. Dans un deuxième temps, nous montrons que suite à une stimulation cutanée, l’ensemble des cellules RS localisées dans les quatre noyaux réticulés possèdent un patron d’activation similaire et elles peuvent toutes produire des dépolarisations soutenues dont le maintien ne dépend pas des réserves de calcium internes. Enfin, les résultats obtenus durant ce doctorat ont permis de mieux comprendre les mécanismes cellulaires par lesquels l’ensemble des cellules RS intègrent une brève information sensorielle et la transforment en une réponse soutenue associée à une commande motrice.

Role of midbrain in the control of breathing in anuran amphibians

The present study was designed to explore systematically the midbrain of unanesthetized, decerebrate anuran amphibians (bullfrogs), using chemical and electrical stimulation and midbrain transections to identify sites capable of exciting and inhibiting breathing. Ventilation was measured as fictive motor output from the mandibular branch of the trigeminal nerve and the laryngeal branch of the vagus nerve. The results of our transection studies suggest that, under resting conditions, the net effect of inputs from sites within the rostral half of the midbrain is to increase fictive breathing frequency, whereas inputs from sites within the caudal half of the midbrain have no net effect on fictive breathing frequency but appear to act on the medullary central rhythm generator to produce episodic breathing. The results of our stimulation experiments indicate that the principal sites in the midbrain that are capable of exciting or inhibiting the fictive frequency of lung ventilation, and potentially clustering breaths into episodes, appear to be those primarily involved in visual and auditory integration, motor functions, and attentional state.

AN ANATOMICAL STUDY OF THE LATEROTRIGEMINAL VENOUS SYSTEM

The middle cranial fossa of 100 cadavers were dissected under stereoscopic loupe in order to identify and systematize the venous vessels located along the lateral margin of the trigeminal cave. The author found that at the sensitive root and trigeminal ganglion level a dural venous canal was present in most individuals examined and that the upper side of this canal communicated with the superior petrosal sinus. However, at the level of the lateral border of the intracranial segment of the mandibular nerve, venous lacunae were found to prevail, and these lacunae communicated with several other venous formations in the peritrigeminal region. The author concludes that the venous vascularization of this area constitutes a major risk in surgical interventions made in the middle cranial fossa. In addition, it is a relevant factor in the hemodynamics of the intracranial circulation.

Seqüência de moebius: Manifestações clínicas e avaliação auditiva

Introduction: Children with Moebius syndrome may present paralysis of cranial nerves III, IV, V, VI, VII, VIII, IX, X and XII, compromising motor and sensorial functions. Hands and feet defects (syndactyly, equinovarus and arthrogryposis) are frequently associated. These manifestations can be attributed to the use of misoprostol during pregnancy to induce abortion. Study design: Clinical prospective. Aim: To evaluate the main clinical manifestations, hearing acuity and possible etiologic factors in children with Moebius syndrome. Material and method: The children were submitted to clinical, otolaryngological and hearing acuity assessment. Hearing acuity was evaluated through behavioral tests, pure tone audiometry, tympanometry and auditory brainstem response (ABR). We investigated possible etiologic factors. Results: Three boys and two girls were evaluated. The main manifestations were: facial paralysis, paralysis of masseter muscle, defects in dental occlusion, retraction of tympanic membrane, equinovarus, oblique palpebral fissure and tongue atrophy. Conductive hearing loss was detected in three children and sensorineural hearing loss in one child. The use of misoprostol during pregnancy was reported by four mothers. Conclusions: The children with Moebius syndrome evaluated in the present study manifested palsies of various cranial nerves, especially V, VII and XII nerves, responsible for motor and sensorial alterations. Inadequate eustachian tube function associated to conductive hearing loss was frequent. The use of misoprostol during pregnancy was reported by the mothers and it was considered a possible etiologic factor.

Estudo da distribuição das proteínas relacionadas às teneurinas no sistema nervoso central de primatas não-humanos (Sapajus spp) e ratos (Rattus norvegicus)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)