RESUMO
Data on the state of sense of smell in patients who had a new coronavirus infection caused by the SARS-CoV-2 virus are currently reduced because of the impairment of the olfactory nerve system. There are practically no results in studies of disorders in the trigeminal nerve system. OBJECTIVE: Qualitative assessment of olfactory disorders after COVID-19 according to the system of olfactory and trigeminal nerves with a targeted assessment of the functional component of olfactory disorders. MATERIAL AND METHODS: We examined 40 patients aged 19 to 66 who had a coronavirus infection. All patients underwent neurological, otorhinolaryngological examinations, olfactometry, filled out the hospital anxiety and depression scale. RESULTS: Anosmia was diagnosed in 5 (12.5%) patients, hyposmia in 21 (52.5%) patients, and normosmia in 14 (35%) patients. Formed: the 1st group - 14 patients (35%) with normogram according to olfactometry; the 2nd group - 26 patients (65%) with anosmia/hyposmia. In the 1st group, disorders of the anxiety-depressive spectrum were significantly more common. In the 2nd group, a low identification of odors was found, lying in the spectrum of fresh, sharp, unpleasant, irritating, compared with sweet and pleasant or neutral, which indicates a predominant lesion of the trigeminal system. CONCLUSION: In patients with complaints of impaired sense of smell after undergoing COVID-19, the possible functional nature of anosmia/hyposmia should be taken into account, which requires the referral of such patients to psychotherapeutic specialists, and the possible entry of olfactory disorders into the 'trigeminal' spectrum.
Assuntos
COVID-19 , Transtornos do Olfato , Nervo Trigêmeo , Humanos , COVID-19/complicações , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Transtornos do Olfato/etiologia , Transtornos do Olfato/fisiopatologia , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/virologia , Nervo Trigêmeo/fisiopatologia , SARS-CoV-2 , Idoso , Olfato/fisiologia , Olfatometria/métodos , Anosmia/etiologia , Anosmia/fisiopatologia , Federação Russa/epidemiologia , Doenças do Nervo Trigêmeo/fisiopatologia , Doenças do Nervo Trigêmeo/etiologia , Doenças do Nervo Trigêmeo/diagnósticoRESUMO
BACKGROUND: Nerve fibers related to pain and temperature sensation in the trigeminal nerve territory converge with the upper cervical spinal nerves from the level of the lower medulla oblongata to the upper cervical cord. This structure is called the trigemino-cervical complex and may cause referred pain in the territory of the trigeminal or upper cervical spinal nerves. CASE SERIES: Here, we report three cases of paroxysmal neuralgia in the occipital region with mild conjunctivitis or a few reddish spots in the ipsilateral trigeminal nerve territory. The patients exhibited gradual progression of these reddish spots evolving into vesicles over the course of several days, despite the absence of a rash in the occipital region. The patients were diagnosed with trigeminal herpes zoster and subsequently received antiherpetic therapy. Remarkably, the neuralgia in the occipital region showed gradual amelioration or complete resolution before the treatment, with no sequelae reported in the occipital region. DISCUSSION: The trigemino-cervical complex has the potential to cause neuralgia in the occipital region, as referred pain, caused by trigeminal herpes zoster. These cases suggest that, even if conjunctivitis or reddish spots appear to be trivial in the trigeminal nerve territory, trigeminal herpes zoster should be considered when neuralgia occurs in the ipsilateral occipital region.
Assuntos
Herpes Zoster , Humanos , Masculino , Feminino , Herpes Zoster/complicações , Pessoa de Meia-Idade , Idoso , Neuralgia/etiologia , Nervo Trigêmeo/fisiopatologia , Neuralgia do Trigêmeo/etiologiaRESUMO
BACKGROUND: This study aimed to determine how nasal airflow measures and trigeminal function vary among patients with chronic rhinosinusitis (CRS) versus healthy controls and whether these measures are correlated with subjective nasal obstruction (SNO), olfactory function, and CRS control. METHODOLOGY: Participants included CRS patients and healthy controls. After a structured medical history, nasal airflow (peak nasal inspiratory flow [PNIF]; active anterior rhinomanometry [AAR]), trigeminal function (trigeminal lateralization test, CO2 sensitivity), and olfactory "Sniffin's Sticks" odor identification test) tests were performed. SNO ratings were also obtained. RESULTS: Sixty-nine participants were included (37 men, 32 women, mean age 51 years). There was no significant difference for objective nasal airflow between patients and controls, but CRS patients had worse SNO, trigeminal function, and olfaction compared to controls. SNO, but not objective nasal airflow tests, was negatively correlated with CO2 sensitivity and odor identification. CONCLUSION: The perception of nasal obstruction does not only depend on nasal airflow, but may also be modulated by trigeminal function and other factors. Thus, the role of objective nasal airflow measures as a sole method of functional nasal obstruction assessment in CRS remains limited.
Assuntos
Obstrução Nasal , Rinite , Rinomanometria , Sinusite , Olfato , Nervo Trigêmeo , Humanos , Sinusite/fisiopatologia , Sinusite/complicações , Obstrução Nasal/fisiopatologia , Pessoa de Meia-Idade , Feminino , Masculino , Doença Crônica , Rinite/fisiopatologia , Rinite/complicações , Olfato/fisiologia , Nervo Trigêmeo/fisiopatologia , Adulto , Estudos de Casos e Controles , Idoso , RinossinusiteRESUMO
BACKGROUND: Central and peripheral sensitization are characterized by widespread hyperalgesia that is manifested by larger pain extent area and reduction in pressure pain threshold (PPT). PPT decreases in patients with migraine not only over the trigeminal cervical complex but also throughout the body. METHODS: A cross-sectional study was adopted to assess the local and widespread hyperalgesia in chronic and episodic migraine patients respect to healthy controls. The guidelines of Andersen's were used to evaluate the PPT bilaterally over 3 muscles in the trigemino-cervical complex (temporalis, sub-occipitalis, trapezius) and over 1 muscle far from this area (tensor fasciae latae). RESULTS: Thirty subjects with episodic migraine (35.8 ± 2.82 years), 30 with chronic migraine (53.03 ± 19.79 years), and 30 healthy controls (29.06 ± 14.03 years) were enrolled. The interaction effect was present for the trapezius muscle with a significant difference between the right and the left side in episodic group (p = 0.003). A group effect was highlighted in all four muscles analyzed such as suboccipital (p < 0.001), temporalis (p > 0.001), trapezius (p < 0.001), and TFL (p < 0.001). PPT was usually higher in the control group than in the episodic group which in turn was characterized by higher PPT values than the chronic group. CONCLUSIONS: People with chronic and episodic migraine presented lower PPT than healthy controls both in the trigeminal and in the extra-trigeminal area. People with chronic migraine presented lower PPT than episodic migraine only in the trigeminal area. Temporalis and sub-occipitalis are the most sensitive muscles in people with chronic and episodic migraine.
Assuntos
Transtornos de Enxaqueca , Limiar da Dor , Humanos , Transtornos de Enxaqueca/fisiopatologia , Transtornos de Enxaqueca/diagnóstico , Estudos Transversais , Feminino , Adulto , Masculino , Limiar da Dor/fisiologia , Pessoa de Meia-Idade , Pressão , Nervo Trigêmeo/fisiopatologia , Hiperalgesia/fisiopatologia , Hiperalgesia/diagnóstico , Medição da Dor/métodos , Doença CrônicaRESUMO
OBJECTIVE: Next to olfactory function, the nose can also perceive chemestetic sensations mediated by the trigeminal nerve. While olfactory dysfunction as a symptom of COVID-19 is well described, there has been little research on the limitation of other nasal sensory inputs due to SARS-CoV-2 infection. The aim of this study was to determine possible limitations of nasal chemesthesis after COVID-19 infection by a psychophysiological diagnostic tool. METHODS: In 65 patients with a PCR-confirmed, former COVID-19 disease, olfaction was tested by means of a sniffin' sticks test, tasting by taste sprays and chemesthesis with a menthol dilution series. The subjective self-assessment of the patients was recorded via a questionnaire. RESULTS: We found a restriction of nasal chemesthesis and the extent correlated with the loss of smell, as well as with the values of the taste score, but not with subjective self-assessment. CONCLUSION: Not only the ability to smell and taste, but also nasal chemesthesis is affected by COVID-19.
Assuntos
COVID-19/fisiopatologia , Transtornos do Olfato/virologia , Limiar Sensorial/fisiologia , Olfato/fisiologia , Nervo Trigêmeo/fisiopatologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE OF REVIEW: Headache is a common symptom of COVID-19 with emerging literature being published on the subject. Although it may seem unspecific, scientific evidence has allowed a better definition of this headache type, revealing relevant associations with other COVID-19 symptoms and prognoses. We therefore sought to highlight the most remarkable findings concerning headache secondary to COVID-19, specifically focusing on epidemiology, characteristics, pathophysiology, and treatments. RECENT FINDINGS: The real prevalence of headache as a symptom of COVID-19 is still unclear ranging from 10 to 70%. Headache mainly has a tension-type-like phenotype, although 25% of individuals present with migraine-like features that also occur in patients without personal migraine history. This finding suggests that a likely pathophysiological mechanism is the activation of the trigeminovascular system. SARS-CoV-2 neurotropism can occur by trans-synaptic invasion through the olfactory route from the nasal cavity, leading to anosmia which has been associated with headache. SARS-CoV-2 protein has been found not only in olfactory mucosa and bulbs but also in trigeminal branches and the trigeminal ganglion, supporting this hypothesis. However, other mechanisms such as brain vessels inflammation due to SARS-CoV-2 damage to the endothelium or systemic inflammation in the context of cytokine storm cannot be ruled out. Interestingly, headache has been associated with lower COVID-19 mortality. No specific treatment for COVID-19 headache is available at present. Studies show that investigating COVID-19 headache represents an opportunity not only to better understand COVID-19 in general but also to advance in the knowledge of both secondary and primary headaches. Future research is therefore warranted.
Assuntos
COVID-19/epidemiologia , Cefaleia/epidemiologia , Anosmia/fisiopatologia , COVID-19/complicações , COVID-19/mortalidade , COVID-19/fisiopatologia , Endotélio Vascular , Cefaleia/etiologia , Cefaleia/fisiopatologia , Cefaleia/terapia , Humanos , Inflamação , Transtornos de Enxaqueca/fisiopatologia , SARS-CoV-2 , Cefaleia do Tipo Tensional/fisiopatologia , Gânglio Trigeminal/fisiopatologia , Gânglio Trigeminal/virologia , Nervo Trigêmeo/fisiopatologia , Nervo Trigêmeo/virologia , Tropismo ViralRESUMO
OBJECTIVE: To explore the cortical areas targeted by acute transcutaneous trigeminal nerve stimulation (TNS) in patients with drug-resistant epilepsy (DRE) using single photon emission computed tomography (SPECT). METHODS: Ten patients with DRE underwent brain SPECT at baseline and immediately after a 20-minute TNS (0.25 ms; 120 Hz; 30 s ON and 30 s OFF) applied bilaterally to the infraorbital nerve. The French Color Standard International Scale was used for qualitative analyses and z-scores were used to calculate the Odds Ratio (OR). RESULTS: At baseline global hypoperfusion (mainly in temporo-mesial, temporo-parietal and fronto-temporal and temporo-occipital areas) was detected in all patients. Following TNS, a global increase in cortical tracer uptake and a significant decrease in median hypoperfusion score were observed. A significant effect favoring a general TNS-induced increase in cortical perfusion (OR = 4.96; p = 0.0005) was detected in 70% of cases, with significant effects in the limbic (p = 0.003) and temporal (p = 0.003) lobes. Quantitative analyses of z-scores confirmed significant TNS-induced increases in perfusion in the temporal (+0.59 SDs; p = 0.001), and limbic (+0.43 SDs; p = 0.03) lobes. CONCLUSION: Short-term TNS is followed a global increase in cortical perfusion, namely in the temporal and limbic lobes. SIGNIFICANCE: The TNS-induced perfusion increase may reflect neurons' activity changes in cortical areas implicated in the epilepsy network.
Assuntos
Encéfalo/diagnóstico por imagem , Circulação Cerebrovascular/fisiologia , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Nervo Trigêmeo/fisiopatologia , Adulto , Encéfalo/fisiopatologia , Epilepsia Resistente a Medicamentos/fisiopatologia , Estimulação Elétrica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Tomografia Computadorizada de Emissão de Fóton ÚnicoAssuntos
COVID-19/fisiopatologia , Transtornos do Olfato/fisiopatologia , Nervo Trigêmeo/fisiopatologia , COVID-19/complicações , COVID-19/diagnóstico , Seguimentos , Humanos , Mucosa Nasal/inervação , Mucosa Nasal/fisiopatologia , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/etiologia , Recuperação de Função Fisiológica/fisiologia , SARS-CoV-2 , Teste de Desfecho Sinonasal , Olfato/fisiologiaRESUMO
BACKGROUND: The trigeminal nerve directly innervates key vascular structures both centrally and peripherally. Centrally, it is known to innervate the brainstem and cavernous sinus, whereas peripherally the trigemino-cerebrovascular network innervates the majority of the cerebral vasculature. Upon stimulation, it permits direct modulation of cerebral blood flow (CBF), making the trigeminal nerve a promising target for the management of cerebral vasospasm. However, trigeminally mediated cerebral vasodilation has not been applied to the treatment of vasospasm. OBJECTIVE: To determine the effect of percutaneous electrical stimulation of the infraorbital branch of the trigeminal nerve (pTNS) on the cerebral vasculature. METHODS: In order to determine the stimulus-response function of pTNS on cerebral vasodilation, CBF, arterial blood pressure, cerebrovascular resistance, intracranial pressure, cerebral perfusion pressure, cerebrospinal fluid calcitonin gene-related peptide (CGRP) concentrations, and the diameter of cerebral vessels were measured in healthy and subarachnoid hemorrhage (SAH) rats. RESULTS: The present study demonstrates, for the first time, that pTNS increases brain CGRP concentrations in a dose-dependent manner, thereby producing controllable cerebral vasodilation. This vasodilatory response appears to be independent of the pressor response induced by pTNS, as it is maintained even after transection of the spinal cord at the C5-C6 level and shown to be confined to the infraorbital nerve by administration of lidocaine or destroying it. Furthermore, such pTNS-induced vasodilatory response of cerebral vessels is retained after SAH-induced vasospasm. CONCLUSION: Our study demonstrates that pTNS is a promising vasodilator and increases CBF, cerebral perfusion, and CGRP concentration both in normal and vasoconstrictive conditions.
Assuntos
Peptídeo Relacionado com Gene de Calcitonina/sangue , Estimulação Elétrica/métodos , Vasoconstrição/fisiologia , Vasodilatação/fisiologia , Vasoespasmo Intracraniano/fisiopatologia , Animais , Circulação Cerebrovascular/fisiologia , Masculino , Ratos , Nervo Trigêmeo/fisiopatologia , Vasoespasmo Intracraniano/sangueRESUMO
BACKGROUND: To determine if trigeminal nerve electrical stimulation (TNS) would be an effective arousal treatment for loss of consciousness (LOC), we applied neuroscientific methods to investigate the role of potential brain circuit and neuropeptide pathway in regulating level of consciousness. METHODS: Consciousness behavioral analysis, Electroencephalogram (EEG) recording, Chemogenetics, Microarray analysis, Milliplex MAP rat peptide assay, Chromatin immune-precipitation (ChIP), Dual-luciferase reporter experiment, Western blot, PCR and Fluorescence in situ hybridization (FISH). RESULTS: TNS can markedly activate the neuronal activities of the lateral hypothalamus (LH) and the spinal trigeminal nucleus (Sp5), as well as improve rat consciousness level and EEG activities. Then we proved that LH activation and upregulated neuropeptide hypocretin are beneficial for promotion of consciousness recovery. We then applied gene microarray experiment and found hypocretin might be mediated by a well-known transcription factor Early growth response gene 1 (EGR1), and the results were confirmed by ChIP and Dual-luciferase reporter experiment. CONCLUSION: This study illustrates that TNS is an effective arousal strategy Treatment for LOC state via the activation of Sp5 and LH neurons and upregulation of hypocretin expression.
Assuntos
Terapia por Estimulação Elétrica/métodos , Neurônios/fisiologia , Nervo Trigêmeo/fisiopatologia , Inconsciência/terapia , Animais , Nível de Alerta/fisiologia , Comportamento Animal/fisiologia , Eletroencefalografia , Masculino , Ratos , Ratos Sprague-Dawley , Resultado do Tratamento , Inconsciência/fisiopatologiaRESUMO
BACKGROUND: Trigeminal-cardiac reflex (TCR) is a brainstem vagus reflex that occurs when any center or peripheral branch of the trigeminal nerve was stimulated or operated on. The typical clinical manifestation is sudden bradycardia with or without blood pressure decline. The rhino-cardiac reflex which is one type of TCR is rare in clinical practice. As the rhino-cardiac reflex caused by disinfection of the nasal cavity is very rare, we report these two cases to remind other anesthesiologists to be vigilant to this situation. CASE PRESENTATION: This case report describes two cases of cardiac arrest caused by rhino-cardiac reflex while disinfecting nasal cavity before endoscopic transsphenoidal removal of pituitary adenomas. Their heart rate all dropped suddenly at the very moment of nasal stimulation and recovered quickly after stimulation was stopped and the administration of drugs or cardiac support. CONCLUSION: Although the occurrence of rhino-cardiac reflex is rare, we should pay attention to it in clinical anesthesia. It is necessary to know the risk factors for preventing it. Once it occurs, we should take active and effective rescue measures to avoid serious complications.
Assuntos
Desinfecção/métodos , Parada Cardíaca/etiologia , Parada Cardíaca/terapia , Neoplasias Hipofisárias/cirurgia , Cuidados Pré-Operatórios/efeitos adversos , Reflexo/fisiologia , Nervo Trigêmeo/fisiopatologia , Adulto , Idoso , Antiarrítmicos/uso terapêutico , Atropina/uso terapêutico , Reanimação Cardiopulmonar/métodos , Eletrocardiografia , Coração/fisiopatologia , Parada Cardíaca/diagnóstico , Humanos , Masculino , Cavidade Nasal/fisiopatologia , Cuidados Pré-Operatórios/métodosRESUMO
BACKGROUND: Photophobia is a potentially debilitating symptom often found in dry eye disease (DE), migraine and traumatic brain injury (TBI). METHODS: We conducted a review of the literature via a PubMed search of English language articles with a focus on how photophobia may relate to a shared pathophysiology across DE, migraine and TBI. RESULTS: DE, migraine and TBI are common conditions in the general population, are often comorbid, and share photophobia as a symptom. Across the three conditions, neural dysregulation of peripheral and central nervous system components is implicated in photophobia in various animal models and in humans. Enhanced activity of the neuropeptide calcitonin gene-related peptide (CGRP) is closely linked to photophobia. Current therapies for photophobia include glasses which shield the eyes from specific wavelengths, botulinum toxin, and inhibition of CGRP and its receptor. Many individuals have persistent photophobia despite the use of these therapies, and thus, development of new therapies is needed. CONCLUSIONS: The presence of photophobia in DE, migraine and TBI suggests shared trigeminothalamic pathophysiologic mechanisms, as explained by central neuroplasticity and hypersensitivity mediated by neuropeptide CGRP. Treatment strategies which target neural pathways (ie, oral neuromodulators, transcutaneous nerve stimulation) should be considered in patients with persistent photophobia, specifically in individuals with DE whose symptoms are not controlled with traditional therapies.
Assuntos
Lesões Encefálicas Traumáticas/fisiopatologia , Síndromes do Olho Seco/fisiopatologia , Transtornos de Enxaqueca/fisiopatologia , Plasticidade Neuronal/fisiologia , Fotofobia/fisiopatologia , Núcleos Talâmicos/fisiopatologia , Nervo Trigêmeo/fisiopatologia , HumanosRESUMO
AIM: Little is known about short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA). We present our experience with SUNCT/SUNA patients to aid identification and management of these disorders. METHODS: A retrospective review of patient records of one orofacial pain clinic was performed. Inclusion criteria was a diagnosis of SUNCT/SUNA confirmed with at least one follow-up visit. RESULTS: Six of the 2464 new patients seen between 2015-2018 met the selection criteria (SUNCT n = 2, SUNA n = 4). Gender distribution was one male to one female and average age of diagnosis was 52 years (range 26-62). Attacks were located in the V1/V2 trigeminal distributions, and five patients reported associated intraoral pain. Pain quality was sharp, shooting, and burning with two patients reporting "numbness". Pain was moderate-severe in intensity, with daily episodes that typically lasted for seconds. Common autonomic features were lacrimation, conjunctival injection, rhinorrhea, and flushing. Frequent triggers were touching the nose or a specific intraoral area. Lamotrigine and gabapentin were commonly used as initial therapy. CONCLUSIONS: Differentiating between SUNCT/SUNA does not appear to be clinically relevant. Presenting symptoms were consistent with those published, except 5/6 patients describing intraoral pain and two patients describing paresthesia.
Assuntos
Doenças do Sistema Nervoso Autônomo/complicações , Dor Facial/etiologia , Transtornos da Cefaleia/etiologia , Transtornos de Enxaqueca , Síndrome SUNCT , Adulto , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Dor Facial/diagnóstico , Dor Facial/tratamento farmacológico , Feminino , Gabapentina/uso terapêutico , Transtornos da Cefaleia/classificação , Humanos , Lamotrigina/uso terapêutico , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/complicações , Estudos Retrospectivos , Síndrome SUNCT/diagnóstico , Síndrome SUNCT/etiologia , Síndrome SUNCT/fisiopatologia , Nervo Trigêmeo/fisiopatologiaRESUMO
Poststroke cognitive impairment (PSCI) is a severe sequela of stroke. There are no effective therapeutic options for it. In this study, we evaluated whether electroacupuncture (EA) on the trigeminal nerve-innervated acupoints could alleviate PSCI and identified the mechanisms in an animal model. The male Sprague-Dawley rat middle cerebral artery occlusion (MCAO) model was used in our study. EA was conducted on the two scalp acupoints, EX-HN3 (Yintang) and GV20 (Baihui), innervated by the trigeminal nerve, for 14 sessions, daily. Morris water maze and novel object recognition were used to evaluate the animal's cognitive performance. Neuroprotection and synaptic plasticity biomarkers were analyzed in brain tissues. Ischemia-reperfusion (I/R) injury significantly impaired spatial and cognition memory, while EA obviously reversed cognitive deterioration to the control level in the two cognitive paradigms. Moreover, EA reversed the I/R injury-induced decrease of brain-derived neurotrophic factor, tyrosine kinase B, N-methyl-D-aspartic acid receptor 1, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor, γ-aminobutyric acid type A receptors, Ca2+/calmodulin-dependent protein kinase II, neuronal nuclei, and postsynaptic density protein 95 expression in the prefrontal cortex and hippocampus. These results suggest that EA on the trigeminal nerve-innervated acupoints is an effective therapy for PSCI, in association with mediating neuroprotection and synaptic plasticity in related brain regions in the MCAO rat model.
Assuntos
Pontos de Acupuntura , Disfunção Cognitiva/metabolismo , Eletroacupuntura , Hipocampo/metabolismo , Infarto da Artéria Cerebral Média/complicações , Plasticidade Neuronal , Córtex Pré-Frontal/metabolismo , Nervo Trigêmeo/fisiopatologia , Animais , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/prevenção & controle , Masculino , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To determine whether erenumab, a new monoclonal antibody to the calcitonin gene-related peptide (CGRP) receptor, exerts functional central effects in migraineurs by performing functional imaging scans on patients treated with erenumab. METHODS: We conducted an fMRI study on 27 patients with migraine using a well-established trigeminal nociceptive paradigm, examining patients before and 2 weeks after administration of the CGRP receptor antibody erenumab 70 mg. RESULTS: Comparing both visit days in all patients (n = 27) revealed that erenumab leads to a decrease in activation in the right thalamus (i.e., contralateral to the stimulated side), right middle temporal gyrus, right lingual gyrus, left operculum, and several clusters on both sides of the cerebellum. Furthermore, when responders (n = 9) and nonresponders (n = 8) of the respective same headache state were compared, we found a significant reduction of hypothalamic activation after the administration of erenumab in responders only (t = 4.78; contrast estimate 29.79 [90% confidence interval 19.53-40.05]). This finding of reduced hypothalamic activation was confirmed when absolute headache days was used as a regressor. INTERPRETATION: These findings suggest that erenumab may not be an exclusively peripheral migraine treatment but has additional central effects. Whether this is due to secondary changes after peripheral modulation of sensory input or indeed represents a direct central mode of action is discussed.
Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Encéfalo , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/farmacologia , Neuroimagem Funcional , Transtornos de Enxaqueca/tratamento farmacológico , Rede Nervosa , Avaliação de Resultados em Cuidados de Saúde , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/administração & dosagem , Conectoma , Feminino , Seguimentos , Humanos , Hipotálamo/diagnóstico por imagem , Hipotálamo/efeitos dos fármacos , Hipotálamo/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/diagnóstico por imagem , Transtornos de Enxaqueca/fisiopatologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/efeitos dos fármacos , Rede Nervosa/fisiopatologia , Nociceptividade/fisiologia , Medição da Dor , Estimulação Física , Receptores de Peptídeo Relacionado com o Gene de Calcitonina/imunologia , Marcadores de Spin , Nervo Trigêmeo/fisiopatologia , Adulto JovemRESUMO
BACKGROUND: Stimulation of the occipital or trigeminal nerves has been successfully used to treat chronic refractory neurovascular headaches such as migraine or cluster headache, and painful neuropathies. Convergence of trigeminal and occipital sensory afferents in the 'trigeminocervical complex' (TCC) from cutaneous, muscular, dural, and visceral sources is a key mechanism for the input-induced central sensitization that may underlie the altered nociception. Both excitatory (glutamatergic) and inhibitory (GABAergic and glycinergic) mechanisms are involved in modulating nociception in the spinal and medullary dorsal horn neurons, but the mechanisms by which nerve stimulation effects occur are unclear. This study was aimed at investigating the acute effects of electrical stimulation of the greater occipital nerve (GON) on the responses of neurons in the TCC to the mechanical stimulation of the vibrissal pad. METHODS: Adult male Wistar rats were used. Neuronal recordings were obtained in laminae II-IV in the TCC in control, sham and infraorbital chronic constriction injury (CCI-IoN) animals. The GON was isolated and electrically stimulated. Responses to the stimulation of vibrissae by brief air pulses were analyzed before and after GON stimulation. In order to understand the role of the neurotransmitters involved, specific receptor blockers of NMDA (AP-5), GABAA (bicuculline, Bic) and Glycine (strychnine, Str) were applied locally. RESULTS: GON stimulation produced a facilitation of the response to light facial mechanical stimuli in controls, and an inhibition in CCI-IoN cases. AP-5 reduced responses to GON and vibrissal stimulation and blocked the facilitation of GON on vibrissal responses found in controls. The application of Bic or Str significantly reduced the facilitatory effect of GON stimulation on the response to vibrissal stimulation in controls. However, the opposite effect was found when GABAergic or Glycinergic transmission was prevented in CCI-IoN cases. CONCLUSIONS: GON stimulation modulates the responses of TCC neurons to light mechanical input from the face in opposite directions in controls and under CCI-IoN. This modulation is mediated by GABAergic and Glycinergic mechanisms. These results will help to elucidate the neural mechanisms underlying the effectiveness of nerve stimulation in controlling painful craniofacial disorders, and may be instrumental in identifying new therapeutic targets for their prevention and treatment.
Assuntos
Nervos Espinhais/fisiopatologia , Nervo Trigêmeo/fisiopatologia , Neuralgia do Trigêmeo/fisiopatologia , Vibrissas , Animais , Cefaleia Histamínica , Estimulação Elétrica , Cabeça , Transtornos da Cefaleia , Masculino , Transtornos de Enxaqueca , Neurônios/fisiologia , Nociceptividade , Ratos , Ratos Sprague-Dawley , Ratos WistarRESUMO
An epileptic seizure can trigger a headache during (ictal) or after (postictal) the termination of the event. Little is known about the pathophysiology of seizure-induced headaches. In the current study, we determined whether a seizure can activate nociceptive pathways that carry pain signals from the meninges to the spinal cord, and if so, to what extent and through which classes of peripheral and central neurons. To achieve these goals, we used single-unit recording techniques and an established animal model of seizure (picrotoxin) to determine the effects of epileptic seizure on the activity of trigeminovascular Aδ-, C-, wide-dynamic range, and high-threshold neurons in male and female rats. Occurrence of seizure activated 54%, 50%, 68%, and 39% of the Aδ-, C-, wide-dynamic range, and high-threshold neurons, respectively. Regardless of their class, activated neurons exhibited a twofold to fourfold increase in their firing, which started immediately (1 min) or up to 90 min after seizure initiation, and lasted as short as 10 min or as long as 120 min. Administration of lidocaine to the dura prevented activation of all neuronal classes but not the initiation or maintenance of the seizure. These findings suggest that all neuronal classes may be involved in the initiation and maintenance of seizure-induced headache, and that their activation patterns can provide a neural substrate for explaining the timing and duration of ictal and possibly postictal headaches. By using seizure, which is evident in humans, this study bypasses controversies associated with cortical spreading depression, which is less readily observed in humans.SIGNIFICANCE STATEMENT This preclinical study provides a neural substrate for ictal and postictal headache. By studying seizure effects on the activity of peripheral (C and Aδ) and central (wide dynamic range and high-threshold) trigeminovascular neurons in intact and anesthetized dura, the findings help resolve two outstanding questions about the pathophysiology of headaches of intracranial origin. The first is that abnormal brain activity (i.e., seizure) that is evident in human (unlike cortical spreading depression) gives rise to specific and selective activation of the different components of the trigeminovascular system, and the second is that the activation of all components of the trigeminovascular pathway (i.e., peripheral and central neurons) depends on activation of the meningeal nociceptors from their receptors in the dura.
Assuntos
Cefaleia/etiologia , Cefaleia/fisiopatologia , Neurônios , Convulsões/complicações , Convulsões/fisiopatologia , Nervo Trigêmeo/fisiopatologia , Anestésicos Locais/farmacologia , Animais , Sistema Nervoso Central/fisiopatologia , Eletroencefalografia , Feminino , Lidocaína/farmacologia , Masculino , Meninges/fisiopatologia , Fibras Nervosas Mielinizadas , Fibras Nervosas Amielínicas , Vias Neurais/fisiopatologia , Nociceptores , Sistema Nervoso Periférico/fisiopatologia , Ratos , Ratos Sprague-Dawley , Medula Espinal/fisiopatologiaRESUMO
The trigeminovagal reflex is a phenomenon that occurs rarely during maxillofacial surgery. Previously described as the oculocardiac reflex, this reflex can occur during ocular and periocular surgery. To be more anatomically precise, it was renamed the trigeminocardiac or trigeminovagal reflex, since stimulation of any part of the trigeminal nerve can elicit this reflex arc. We describe a case of asystole during mobilization of a maxilla following a Le Fort 1 osteotomy.