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1.
J Clin Neurophysiol ; 36(6): 437-442, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31688327

RESUMO

Invasive vagus nerve stimulation (VNS) is an approved treatment for drug-resistant epilepsy. Besides recognized clinical efficacy in about 60% of patients, there are major drawbacks such as invasiveness and common side effects including hoarseness, sore throat, shortness of breath, and coughing. Invasive VNS applies electrical stimulation to the left cervical branch of the vagus nerve and excites thick-myelinated afferent nerve fibers. Peripheral vagus nerve afferent volley initiates brainstem activity in the nucleus of the solitary tract and provokes typical brainstem and cerebral activation patterns that mediate the anticonvulsive mode of action. Whereas invasive VNS is an established neuromodulatory treatment in drug-resistant epilepsy, transcutaneous VNS (tVNS) of the auricular branch of the vagus nerve is suggested to be an alternative access path to the same neuronal network without invasiveness. Preclinical and clinical studies indicate that especially the cymba conchae of the auricle is selectively supplied by the auricular branch of the vagus nerve. Recent anatomical data demonstrate existence and quantity of thick-myelinated afferent nerve fibers of the left auricular branch of the vagus nerve that carries 21% of thick-myelinated afferent nerve fibers counted in the left thoracic vagus nerve in humans. Projection of auricular branch of the vagus nerve afferents from the auricle to the nucleus of the solitary tract is known from histochemical and electrophysiological experiments in rodents and confirmed in humans by functional imaging. Cerebral activation patterns triggered by invasive and tVNS resemble each other in appearance. Clinical trials in patients address safety and performance of tVNS and provide evidence for application in drug-resistant epilepsy.


Assuntos
Epilepsia Resistente a Medicamentos/terapia , Estimulação Elétrica Nervosa Transcutânea/métodos , Estimulação do Nervo Vago/métodos , Animais , Epilepsia Resistente a Medicamentos/fisiopatologia , Humanos , Nervo Vago/fisiologia
2.
J Med Internet Res ; 21(1): e10885, 2019 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-30674449

RESUMO

BACKGROUND: Perception of stimuli presented in a virtual dentistry environment affects regions of the brain that are related to pain perception. OBJECTIVE: We investigated whether neural correlates of virtual pain perception are affected by education in dentistry. METHODS: In this functional magnetic resonance imaging study, a sample of 20 dental students and 20 age-matched controls viewed and listened to video clips presenting a dental treatment from the first-person perspective. An anxiety questionnaire was used to assess the level of dental anxiety. Neural correlates of pain perception were investigated through classic general linear model analysis and in-house classification methods. RESULTS: Dental students and naïve controls exhibited similar anxiety levels for invasive stimuli. Invasive dentistry scenes evoked a less affective component of pain in dental students compared with naïve controls (P<.001). Reduced affective pain perception went along with suppressed brain activity in pain matrix regions including the insula, anterior cingulate cortex, and basal ganglia. Furthermore, a substantial reduction of brain activity was observed in motor-related regions, particularly the supplementary motor area, premotor cortex, and basal ganglia. Within this context, a classifier analysis based on neural activity in the nucleus lentiformis could identify dental students and controls on the individual subject level in 85% of the cases (34 out of 40 participants, sensitivity=90%, specificity=80%). CONCLUSIONS: Virtual dental treatment activates pain-related brain regions in controls. By contrast, dental students suppress affective and motor-related aspects of pain. We speculate that dental students learn to control motoric aspects of pain perception during their education because it is a prerequisite for the professional manual treatment of patients. We discuss that a specific set of learning mechanisms might affect perceived self-efficacy of dental students, which in turn might reduce their affective component of pain perception.


Assuntos
Encéfalo/fisiopatologia , Imagem por Ressonância Magnética/métodos , Dor/psicologia , Adulto , Humanos , Masculino , Percepção
3.
Acta Odontol Scand ; 75(5): 338-344, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28372503

RESUMO

OBJECTIVE: Cigarette smoking is associated with a variety of oral diseases. A previous study showed a reduction of thermal sensitivity in the innervation area of the lingual nerve in smokers possibly caused by a degeneration of thermosensitive receptors as a consequence of smoking. The current study investigates somatosensory changes in ex-smokers. MATERIALS AND METHODS: Sensory functions in innervation areas of lingual nerve were investigated in 40 ex-smokers by psychophysical means. Functions of lingual nerve in 40 ex-smokers were compared to those in 40 smokers and 40 non-smokers. Subjects were investigated using quantitative sensory testing (QST, cold and warm detection, thermal sensory limen, heat and cold pain, and mechanical detection). RESULTS: Significant differences were found in both groups, ex-smokers and smokers compared to non-smokers. Cold (p < .001), warm (ex-smokers: p < .01; smokers: p < .001) detection thresholds and thermal sensory limen (p < .001) showed significantly lower sensitivity in ex-smokers and smokers in comparison to non-smokers. CONCLUSIONS: The lower temperature sensitivity of ex-smokers compared to that in non-smokers indicates a reduction of somatosensory function of the tongue, possibly caused by irreversible nerve degeneration associated with smoking. Influencing factors leading to sensory changes could be modulation of thermo-receptors, demyelination as well as a change of the epithelial structure.


Assuntos
Nervo Lingual/fisiopatologia , Fumar/fisiopatologia , Sensação Térmica , Língua/fisiopatologia , Adulto , Temperatura Baixa , Feminino , Temperatura Alta , Humanos , Masculino , Pessoa de Meia-Idade , Limiar Sensorial/fisiologia , Abandono do Hábito de Fumar , Língua/inervação
4.
J Headache Pain ; 17(1): 75, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27565510

RESUMO

BACKGROUND: Tension-type headache and other primary headaches may be triggered or aggravated by disorders of pericranial muscles, which is possibly due to convergent or collateral afferent input from meningeal and muscular receptive areas. In rodent models high extracellular concentrations of ATP caused muscle nociception and central sensitization of second order neurons. In a rat model of meningeal nociception we asked if spinal trigeminal activity induced by ATP can be modulated by local anaesthesia of distinct muscles. METHODS: Ongoing activity was recorded from spinal trigeminal neurons with afferent input from the cranial dura mater, the temporal muscle and neck muscles. The stable ATP analogue α,ß-methylene adenosine 5'-triphosphate (α,ß-meATP, 10 mM) was injected into the ipsilateral temporal muscle, 30 min later followed by injection of local anaesthetics (lidocaine, 2 %) into the ipsilateral neck muscles and/or the temporal muscle. RESULTS: Injection of α,ß-meATP into the temporal muscle caused progressive increase in ongoing activity of most of the spinal trigeminal neurons within 30 min. Injection of lidocaine into the neck muscles and/or the temporal muscle reduced this activation to previous levels within 10 min. CONCLUSIONS: Distinct spinal trigeminal neurons processing meningeal nociceptive information are under the control of convergent afferent input from several pericranial muscles. Blockade of at least one of these inputs can normalize central trigeminal activity. This may explain why therapeutic manipulations of head muscles can be beneficial in primary headaches.


Assuntos
Dura-Máter/patologia , Músculo Esquelético/patologia , Neurônios Aferentes/patologia , Cefaleia do Tipo Tensional/patologia , Trifosfato de Adenosina/farmacologia , Animais , Modelos Animais de Doenças , Dura-Máter/fisiologia , Lidocaína/farmacologia , Masculino , Músculo Esquelético/inervação , Neurônios/fisiologia , Ratos , Ratos Wistar
5.
Anat Rec (Hoboken) ; 299(9): 1184-91, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27342906

RESUMO

Transcutaneous stimulation of the auricular branch of the vagus nerve (ABVN) resulted in deactivation of temporal lobe structures, similar to invasive cervical vagus nerve (CVN) stimulation. Presumably, both methods stimulated myelinated afferent beta axons mediating anti-convulsive effects. How numbers of A beta axons in the human ABVN compare to those of the CVN is unknown. The ABVN, CVN, recurrent laryngeal nerve (RLN) and thoracic vagus nerve (TVN) were dissected from embalmed bodies. Numbers and calibers of myelinated axons were analyzed in semithin sections. Myelinated axons in the left and right ABVN averaged to 385 and 363, respectively. Numbers of A beta axons measuring ≥7 µm averaged to 64 and 78 on the left and right, respectively. Numbers of A beta axons in CVN were estimated by subtracting myelinated presumed motor axons in RLN from the total count of CVN. This resulted in 280 and 504 A beta axons on the left and right, respectively, concurring well with the thick myelinated axon count of the ipsilateral TVN (255 and 466, respectively). Thus, the ratio of A beta axons in the ABVN and CVN was ∼1:5 and 1:6 on the left and right side, respectively. These results indicate that transcutaneous ABVN stimulation might be a promising alternative to invasive CVN stimulation. Anat Rec, 299:1184-1191, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Axônios , Fibras Nervosas Mielinizadas , Nervo Vago/anatomia & histologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
6.
Brain Stimul ; 8(3): 624-36, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25573069

RESUMO

BACKGROUND: Tract-tracing studies in cats and rats demonstrated that the auricular branch of the vagus nerve (ABVN) projects to the nucleus tractus solitarii (NTS); it has remained unclear as to whether or not the ABVN projects to the NTS in humans. OBJECTIVE: To ascertain whether non-invasive electrical stimulation of the cymba conchae, a region of the external ear exclusively innervated by the ABVN, activates the NTS and the "classical" central vagal projections in humans. METHODS: Twelve healthy adults underwent two fMRI scans in the same session. Electrical stimulation (continuous 0.25ms pulses, 25Hz) was applied to the earlobe (control, scan #1) and left cymba conchae (scan #2). Statistical analyses were performed with FSL. Two region-of-interest analyses were performed to test the effects of cymba conchae stimulation (compared to baseline and control, earlobe, stimulation) on the central vagal projections (corrected; brainstem P < 0.01, forebrain P < 0.05), followed by a whole-brain analysis (corrected, P < 0.05). RESULTS: Cymba conchae stimulation, compared to earlobe (control) stimulation, produced significant activation of the "classical" central vagal projections, e.g., widespread activity in the ipsilateral NTS, bilateral spinal trigeminal nucleus, dorsal raphe, locus coeruleus, and contralateral parabrachial area, amygdala, and nucleus accumbens. Bilateral activation of the paracentral lobule was also observed. Deactivations were observed bilaterally in the hippocampus and hypothalamus. CONCLUSION: These findings provide evidence in humans that the central projections of the ABVN are consistent with the "classical" central vagal projections and can be accessed non-invasively via the external ear.


Assuntos
Encéfalo/fisiologia , Orelha Externa/inervação , Orelha Externa/fisiologia , Núcleo Solitário/fisiologia , Nervo Vago/fisiologia , Adulto , Idoso , Tonsila do Cerebelo/fisiologia , Córtex Cerebral/fisiologia , Estimulação Elétrica , Feminino , Humanos , Hipotálamo/fisiologia , Locus Cerúleo/fisiologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estimulação do Nervo Vago , Adulto Jovem
7.
Prosthet Orthot Int ; 39(6): 444-53, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24898556

RESUMO

BACKGROUND: An ankle-foot orthosis is suggested to actively assist dorsiflexion of the foot by induction of a positive proprioceptive impact to ankle dorsiflexor muscles. However, an objective proof is missing. OBJECTIVES: To assess the proprioceptive impact of an ankle-foot orthosis application by Hoffmann reflex recordings of the soleus muscle under static conditions. It was hypothesized that the use of an ankle-foot orthosis facilitated dorsiflexor motor function and thus a decreased the soleus Hoffmann reflex. STUDY DESIGN: Experimental study in healthy volunteers, pre-post test design. METHODS: In all, 20 healthy volunteers were enrolled in order to assess the proprioceptive impact of orthosis application. The Hoffmann reflex was recorded before, during, and after orthosis application. RESULTS: Under orthosis application, the Hoffmann reflex significantly decreased as compared to before (p < 0.05) and after application (p < 0.05). CONCLUSIONS: Findings indicate an inhibition of plantarflexors probably induced by facilitation of ankle dorsiflexors under static conditions. At first glance, it seems that foot orthoses primarily have a stabilizing effect on ankle joints in terms of simple mechanical bandages. However, the present results suggest an additional active impact on proprioceptive control. CLINICAL RELEVANCE: The putative neuromodulatory effect on motor control may support the application of such ankle-foot orthoses in, for example, drop foot. Furthermore, the objective assessment of a neurophysiological mode of action of orthoses by Hoffmann reflex recordings might be an appropriate primary outcome parameter in clinical trials.


Assuntos
Órtoses do Pé , Músculo Esquelético/fisiologia , Propriocepção/fisiologia , Reflexo Anormal/fisiologia , Análise de Variância , Tornozelo/fisiologia , Feminino , Pé/fisiologia , Voluntários Saudáveis , Humanos , Masculino , Valores de Referência , Adulto Jovem
8.
Int J Neurosci ; 125(7): 475-85, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25526555

RESUMO

The proceedings of the 2nd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, and computational work on DBS for the treatment of neurological and neuropsychiatric disease and represent the insights of a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers and members of industry. Presentations and discussions covered a broad range of topics, including advocacy for DBS, improving clinical outcomes, innovations in computational models of DBS, understanding of the neurophysiology of Parkinson's disease (PD) and Tourette syndrome (TS) and evolving sensor and device technologies.


Assuntos
Estimulação Encefálica Profunda/métodos , Cooperação Internacional , Doença de Parkinson/terapia , Síndrome de Tourette/terapia , Animais , Encéfalo/fisiologia , Humanos
9.
Neuromodulation ; 17(7): 686-94; discussion 694-5, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24237769

RESUMO

OBJECTIVES: Electrical peripheral nerve stimulation (PNS) is discussed as an effective neuromodulatory treatment in chronic pain. This human experimental study hypothesized a rightward shift of stimulus-response function as a marker of antinociceptive and analgesic PNS effects. MATERIALS AND METHODS: Innocuous electrical PNS of the left superficial radial nerve trunk evoked paresthesia on the left hand dorsum in 29 healthy volunteers. In this innervation area, laser stimulation was performed before, during, and after PNS. Ten different laser intensities ranging between perception and tolerance thresholds were applied. Cortical laser-evoked potentials (LEP) were recorded, and perceptual ratings were documented. Data were analyzed in low, medium, and high laser intensity categories. Stimulus-response functions were calculated. Laser detection and pain thresholds were interpolated. RESULTS: Interpolated laser thresholds after logarithmic regression were not different from measured thresholds. Laser pain threshold increased during and after PNS. LEP amplitude decreased at medium and high intensities under PNS. Ratings transiently decreased during PNS at medium and high laser intensities. CONCLUSIONS: Modulation of laser pain threshold, perceptual ratings, and LEP indicates a rightward shift of stimulus-response function under PNS. These data emphasize antinociceptive and analgesic effects of PNS in an experimental human model and support its clinical neuromodulative relevance.


Assuntos
Dor Crônica/terapia , Limiar da Dor/fisiologia , Nervos Periféricos/fisiologia , Pele/inervação , Análise de Variância , Córtex Cerebral/fisiopatologia , Dor Crônica/etiologia , Eletroencefalografia , Potenciais Somatossensoriais Evocados/fisiologia , Feminino , Lateralidade Funcional , Voluntários Saudáveis , Humanos , Hiperalgesia/etiologia , Lasers/efeitos adversos , Masculino
10.
Brain Stimul ; 6(2): 202-9, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22621941

RESUMO

BACKGROUND: Recent preclinical work strongly suggests that vagus nerve stimulation efficiently modulates nociception and pain processing in humans. Most recently, a medical device has offered a transcutaneous electrical stimulation of the auricular branch of the vagus nerve (t-VNS) without any surgery. OBJECTIVE: Our study investigates whether t-VNS may have the potential to alter pain processing using a controlled design. METHODS: Different submodalities of the somatosensory system were assessed with quantitative sensory testing (QST) including a tonic heat pain paradigm in 48 healthy volunteers. Each subject participated in two experimental sessions with active t-VNS (stimulation) or sham t-VNS (no stimulation) on different days in a randomized order (crossed-over). One session consisted of two QST measurements on the ipsi- and contralateral hand, each before and during 1 h of a continuous t-VNS on the left ear using rectangular pulses (250 µS, 25 Hz). RESULTS: We found an increase of mechanical and pressure pain threshold and a reduction of mechanical pain sensitivity. Moreover, active t-VNS significantly reduced pain ratings during sustained application of painful heat for 5 min compared to sham condition. No relevant alterations of cardiac or breathing activity or clinical relevant side effects were observed during t-VNS. CONCLUSIONS: Our findings of a reduced sensitivity of mechanically evoked pain and an inhibition of temporal summation of noxious tonic heat in healthy volunteers may pave the way for future studies on patients with chronic pain addressing the potential analgesic effects of t-VNS under clinical conditions.


Assuntos
Percepção da Dor/fisiologia , Limiar da Dor/fisiologia , Estimulação Elétrica Nervosa Transcutânea , Estimulação do Nervo Vago , Adulto , Estudos Cross-Over , Método Duplo-Cego , Feminino , Resposta Galvânica da Pele/fisiologia , Temperatura Alta , Humanos , Masculino , Medição da Dor , Estimulação Física
11.
Epilepsia ; 53(7): e115-8, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22554199

RESUMO

To elucidate, in a pilot-study, whether noninvasive transcutaneous vagus nerve stimulation (t-VNS) is a safe and tolerable alternative treatment option in pharmacoresistant epilepsy. t-VNS was applied to 10 patients with pharmacoresistant epilepsies. Stimulation via the auricular branch of the vagus nerve of the left tragus was delivered three times per day for 9 months. Subjective documentation of stimulation effects was obtained from patients' seizure diaries. For a more reliable assessment of seizure frequency, we carried out prolonged outpatient video-electroencephalography (EEG) monitoring. In addition, computerized testing of cognitive, affective, and emotional functions was performed. Three patients aborted the study. Of the remaining seven patients, an overall reduction of seizure frequency was observed in five patients after 9 months of t-VNS. The noninvasive t-VNS stimulation is a safe and well-tolerated method for relatively long periods, and might be an alternative treatment option for patients with epilepsy.


Assuntos
Epilepsia/terapia , Pele/inervação , Estimulação do Nervo Vago/métodos , Adolescente , Adulto , Antieméticos/efeitos adversos , Cognição/fisiologia , Orelha/inervação , Eletroencefalografia , Emoções , Epilepsia/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Gravação em Vídeo , Adulto Jovem
12.
Cephalalgia ; 32(7): 544-53, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22529194

RESUMO

INTRODUCTION: Facilitation of neck muscle nociception mediated via purinergic signalling may play a role in the pathophysiology of tension-type headache (TTH). The present study addressed reversal of purinergic facilitation of brainstem nociception via P2X7 antagonist action in anaesthetized mice. METHODS: Following administration of α,ß-meATP (i.m. 20 µL/min, 20 µL each) into semispinal neck muscles, the impact of neck muscle nociceptive input on brainstem processing was monitored by the jaw-opening reflex in anaesthetized mice (n = 20). The hypothesized involvement of the P2X7 receptor in the α,ß-meATP effect was addressed with i.p. (systemic) and i.m. (semispinalis, 20 µL/min, 20 µL each) administration of P2X7 inhibitor A438079 during established facilitation; i.p. saline served as control. RESULTS: α,ß-meATP reliably induced jaw-opening reflex facilitation (256 ± 48% (mean ± SEM), n = 20). I.p. A438079 (150, 300 µmol/kg) completely reversed this α,ß-meATP effect dose-dependently. Neither saline nor intramuscular A438079 (100 µM) altered facilitated brainstem nociceptive processing. DISCUSSION: These data suggest that muscular structures are not directly involved in the P2X7 antagonist-mediated reversal of purinergic facilitation. Instead, involvement of neuronal structures, particularly of the central nervous system, seems more probable. The results from this animal experimental model may point to involvement of purinergic P2X7 receptors in TTH pathophysiology and may suggest potential future targets for its pharmacological treatment.


Assuntos
Antagonistas do Receptor Purinérgico P2X/farmacologia , Piridinas/farmacologia , Receptores Purinérgicos P2X7/fisiologia , Cefaleia do Tipo Tensional/tratamento farmacológico , Cefaleia do Tipo Tensional/fisiopatologia , Tetrazóis/farmacologia , Trifosfato de Adenosina/análogos & derivados , Trifosfato de Adenosina/farmacologia , Animais , Tronco Encefálico/fisiopatologia , Arcada Osseodentária/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculos do Pescoço/inervação , Músculos do Pescoço/fisiopatologia , Nociceptores/efeitos dos fármacos , Nociceptores/fisiologia , Reflexo/efeitos dos fármacos , Reflexo/fisiologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
13.
Clin Oral Investig ; 16(1): 39-44, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20938792

RESUMO

Smoking has been indicated as a risk factor for oral diseases and can lead to altered sense of taste. So far, the effects of sensory changes on the tongue are not investigated. In this study, quantitative sensory testing was used to evaluate somatosensory function in the lingual region. Eighty healthy volunteers were investigated (20 smokers, 20 non-smokers). Subjects were bilaterally tested in innervation areas of lingual nerves. Thresholds of cold and warm detection, cold and heat pain, and mechanical detection were determined. As control for systemic, extraoral effects of smoking, tests were additionally performed in 40 volunteers (20 smokers, 20 non-smokers) on the skin of the chin innervated by the mental branch of the trigeminal nerve. Cold (p < 0.001), warm detection thresholds (p < 0.001), and thermal sensory limen (p < 0.001) showed higher sensitivity in non-smokers as compared to smokers. Heat pain and mechanical detection, as well as all tests in the skin of the chin, showed no significant differences. The impaired temperature perception in smokers indicates a reduction of somatosensory functions in the tongue, possibly caused by nerve degeneration associated with smoking. Possible systemic effects of smoking do not seem to affect extraoral trigeminal branches.


Assuntos
Sensação/fisiologia , Fumar/fisiopatologia , Língua/fisiopatologia , Adulto , Queixo/inervação , Temperatura Baixa , Feminino , Temperatura Alta , Humanos , Nervo Lingual/fisiopatologia , Lábio/inervação , Masculino , Pessoa de Meia-Idade , Limiar da Dor/fisiologia , Limiar Sensorial/fisiologia , Fatores Sexuais , Pele/inervação , Sensação Térmica/fisiologia , Língua/inervação , Tato/fisiologia , Nervo Trigêmeo/fisiologia , Adulto Jovem
14.
Eur J Pharmacol ; 673(1-3): 13-9, 2011 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-22032900

RESUMO

Infusion of α,ß-methylene ATP (α,ß-meATP) into murine neck muscle facilitates brainstem nociception. This animal experimental model is suggested to be appropriate for investigating pathophysiological mechanisms in tension-type headache. It was hypothesized that d-lysine acetylsalicylic acid (ASA, aspirin®) reverses this α,ß-meATP effect. Facilitation of neck muscle nociceptive processing was induced via bilateral infusion of α,ß-meATP into semispinal neck muscles (100 nM, 20 µl each) in 42 anesthetized mice. Brainstem nociception was monitored by the jaw-opening reflex elicited via electrical tongue stimulation. The hypothesis was addressed by subsequent (15, 30, 60 mg/kg) and preceding (60 mg/kg) intraperitoneal ASA injection. Saline served as control to ASA solution. Subsequent ASA dose-dependently reversed α,ß-meATP-induced reflex facilitation and was the most prominent with 60 mg/kg. Preceding 60 mg/kg ASA prevented reflex facilitation. Cyclooxygenases are involved in nociceptive transmission. Former experiments showed that unspecific inhibition of cyclooxygenases does not alter the α,ß-meATP effect. This suggests a specific mode of action of ASA. The concept is accepted that neck muscle nociception is involved in the pathophysiology of tension-type headache. Thus, objective proof of ASA effects in this experimental model may emphasize its major role in pharmacological treatment of tension-type headache attacks.


Assuntos
Trifosfato de Adenosina/análogos & derivados , Aspirina/farmacologia , Nociceptividade/efeitos dos fármacos , Cefaleia do Tipo Tensional/tratamento farmacológico , Trifosfato de Adenosina/administração & dosagem , Trifosfato de Adenosina/farmacologia , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacologia , Aspirina/administração & dosagem , Inibidores de Ciclo-Oxigenase/administração & dosagem , Inibidores de Ciclo-Oxigenase/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculos do Pescoço/efeitos dos fármacos , Músculos do Pescoço/fisiopatologia , Cefaleia do Tipo Tensional/fisiopatologia
15.
Exp Brain Res ; 212(2): 189-98, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21553262

RESUMO

Electrical low-frequency stimulation (LFS) evokes long-term depression (LTD) of nociception. Human studies suggested a strictly homotopic organization. This study hypothesizes that even heterotopic LFS evokes LTD within the same receptive field (RF). In 33 healthy volunteers, painful electrical test stimulation and LFS were applied to the low back by a concentric electrode (ExpBack) and to the forearm by a multiarray electrode (ExpArm). Volunteers rated pain perception during test stimulation that was applied before and after LFS. In ExpBack, test stimuli were administered within the right T12 dermatome. LFS was applied heterotopically within the same RF or remote in dermatome T8. In ExpArm, test stimulation was carried out in the center of the RF whereas LFS was applied to the center, margin, or outside the RF. In ExpBack (n = 20), pain ratings decreased significantly stronger in T12 than in T8 dermatome (P < 0.01). In ExpArm (n = 20), LFS to the center of the RF induced a stronger pain reduction than LFS applied outside the RF (P < 0.001). This study demonstrates a heterosynaptic organization of LTD within the same RF. Profound knowledge about RF involvement on LTD seems crucial in order to judge the quality of LFS as a possible neuromodulatory treatment of pain.


Assuntos
Terapia por Estimulação Elétrica/métodos , Depressão Sináptica de Longo Prazo/fisiologia , Manejo da Dor , Medição da Dor/métodos , Adulto , Feminino , Humanos , Potenciação de Longa Duração/fisiologia , Masculino , Plasticidade Neuronal/fisiologia , Dor/fisiopatologia , Adulto Jovem
16.
Headache ; 51(5): 734-43, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21434910

RESUMO

BACKGROUND: Neck muscle nociception mediated by nitric oxide may play a role in the pathophysiology of tension-type headache. OBJECTIVE: The present study addresses the involvement of neuronal nitric oxide synthase (nNOS) in the facilitation of neck muscle nociception after local application of nerve growth factor (NGF). METHODS: After administration of NGF into semispinal neck muscles, the impact of neck muscle noxious input on brainstem processing was monitored by the jaw-opening reflex in anesthetized mice. The modulatory effect of preceding and subsequent administration of an inhibitor of neuronal nitric oxide synthase on central facilitation was addressed in a controlled study. RESULTS: With preceding i.p. application of saline or 0.096 mg/kg of the specific nNOS inhibitor Nω-propyl-L-arginine (NPLA), NGF induced a sustained reflex facilitation within 60 minutes. Preceding injection of 0.96 mg/kg or 1.92 mg/kg NPLA completely prevented the potentially facilitatory effect of NGF. Subsequent administration of 0.96 mg/kg NPLA did not affect established NGF-evoked reflex facilitation. Thus, NPLA prevents facilitation of brainstem processing by noxious myofascial input from neck muscles in a dose-dependent manner. CONCLUSION: These findings suggest that nNOS is involved in the induction but not the maintenance of NGF-evoked facilitation of nociception in the brainstem. These results from an experimental animal model may support the idea of NOS and nNOS as potential targets for pharmacological treatment of tension-type headache.


Assuntos
Músculos do Pescoço/inervação , Óxido Nítrico Sintase Tipo I/metabolismo , Dor/enzimologia , Cefaleia do Tipo Tensional/enzimologia , Animais , Arginina/análogos & derivados , Arginina/farmacologia , Tronco Encefálico/enzimologia , Modelos Animais de Doenças , Estimulação Elétrica , Inibidores Enzimáticos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculos do Pescoço/efeitos dos fármacos , Músculos do Pescoço/fisiopatologia , Fator de Crescimento Neural/toxicidade , Dor/fisiopatologia , Reflexo/efeitos dos fármacos , Cefaleia do Tipo Tensional/induzido quimicamente , Cefaleia do Tipo Tensional/fisiopatologia
17.
Eur J Pharmacol ; 647(1-3): 55-61, 2010 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-20813105

RESUMO

Infusion of α,ß-methylene ATP (α,ß-meATP) into murine neck muscle facilitates brainstem nociception. Unspecific nitric oxide synthase (NOS) inhibition prevents and reverses this sensitization. It is unclear whether neuronal (nNOS), inducible (iNOS) or endothelial NOS isoenzymes are involved in this α,ß-meATP effect. Hypothesized involvement of nNOS isoenzyme was addressed by preceding (0.5, 1, and 2 mg/kg) and subsequent (2 mg/kg) intraperitoneal injection of the nNOS-inhibitor NPLA. iNOS involvement was addressed by subsequent, intraperitoneal administration of the iNOS-inhibitor 1400 W (2 mg/kg). Brainstem nociception was monitored by the jaw-opening reflex elicited via electrical tongue stimulation in 45 anesthetized mice. Preceding NPLA dose-dependently prevented α,ß-meATP-induced reflex facilitation. Whereas subsequent inhibition of nNOS showed no effect, iNOS inhibition by 1400 W significantly reversed reflex facilitation. Data provide evidence that nNOS plays a major role in induction and iNOS in maintenance of facilitation in neck muscle nociception. Divergent roles of NOS isoenzymes may promote research on target specific treatment for headache and neck muscle pain.


Assuntos
Trifosfato de Adenosina/análogos & derivados , Músculos do Pescoço/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo I/antagonistas & inibidores , Nociceptores/efeitos dos fármacos , Cefaleia do Tipo Tensional/tratamento farmacológico , Trifosfato de Adenosina/metabolismo , Trifosfato de Adenosina/fisiologia , Animais , Arginina/administração & dosagem , Arginina/análogos & derivados , Arginina/farmacologia , Inibidores Enzimáticos/farmacologia , Iminas/administração & dosagem , Iminas/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculos do Pescoço/fisiopatologia , Reflexo/efeitos dos fármacos , Cefaleia do Tipo Tensional/fisiopatologia
18.
Cephalalgia ; 30(10): 1225-32, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20855368

RESUMO

INTRODUCTION: Tension-type headache (TTH) is associated with noxious input from neck muscles. Intravenous administration of the unspecific nitric oxide synthase inhibitor L-NMMA in chronic TTH patients caused analgesia and reduction of neck muscle tenderness. METHODS: The unspecific nitric oxide synthase inhibitor L-NMMA was applied in an experimental model for neck muscle nociception in anesthetized mice (N = 25). RESULTS: Local injection of α,ß-meATP into semispinal neck muscles induced sustained facilitation of brainstem nociception as monitored by the jaw-opening reflex. Preceding intraperitoneal administration of L-NMMA (0.05, 0.1, 1 mg/kg) prevented reflex facilitation evoked by α,ß-meATP in a dose-dependent manner. Intraperitoneal injection of L-NMMA subsequent to intramuscular α,ß-meATP application reversed established brainstem reflex facilitation back to baseline values. DISCUSSION: Both experiments with preceding and subsequent L-NMMA indicate the involvement of nitric oxide synthases in the induction and maintenance of facilitation. However, future experiments will have to address the involvement of various isoenzymes in order to provide for new therapeutic concepts in TTH.


Assuntos
Inibidores Enzimáticos/farmacologia , Músculos do Pescoço/efeitos dos fármacos , Cervicalgia/prevenção & controle , ômega-N-Metilarginina/farmacologia , Trifosfato de Adenosina/análogos & derivados , Trifosfato de Adenosina/toxicidade , Animais , Antineoplásicos/toxicidade , Eletrofisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Cervicalgia/induzido quimicamente , Óxido Nítrico Sintase/antagonistas & inibidores
19.
Cephalalgia ; 30(7): 860-7, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20647178

RESUMO

Repetitive low-frequency electrical stimulation (LFS) induces pain inhibition in healthy volunteers and in animals, but it is unknown whether it has an analgesic effect in patients with headache. The aim of this study was to investigate if LFS could induce prolonged pain inhibition, called long-term depression (LTD), in patients with chronic tension-type headache (CTTH). Twenty CTTH patients and 20 healthy volunteers were exposed to 20 min LFS (1 Hz) to the forehead. LTD was measured as a decrease in pain response to electrical stimulation in a 1-h post-LFS period following LFS. The LFS induced a significant and stable inhibition of pain (LTD) both in patients with CTTH (post-LFS average decrease in pain rating: 19.6 +/- 3.9%, all P < 0.005, Holm-Sidak) and in healthy controls (30.1 +/- 5.0%, all P < 0.001, Holm-Sidak). During the LFS period, the pain ratings decreased consistently in both groups. In conclusion, a significant and stable pain inhibition (LTD) can be induced in CTTH patients by LFS.


Assuntos
Terapia por Estimulação Elétrica/métodos , Depressão Sináptica de Longo Prazo/fisiologia , Cefaleia do Tipo Tensional/terapia , Doença Crônica , Feminino , Humanos , Masculino , Dor/etiologia , Manejo da Dor , Cefaleia do Tipo Tensional/complicações
20.
J Oral Maxillofac Surg ; 68(10): 2437-51, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20598414

RESUMO

PURPOSE: Orofacial sensory dysfunction plays an important role in oral and maxillofacial surgery. Quantitative sensory testing (QST) is a psychophysical approach to evaluate thermal and mechanical somatosensation. PATIENTS AND METHODS: The present human study 1) collected normative QST data in extraoral and intraoral regions, 2) analyzed effects of age, gender, and anatomical sites on QST, and 3) applied QST in 11 patients with iatrogenic inferior alveolar nerve lesions. Sixty (30 male and 30 female) healthy volunteers were tested bilaterally in the innervation areas of infraorbital, mental, and lingual nerves. Ten patients with sensory disturbances in innervation areas of the mental nerve were investigated at 1, 4, and 8 weeks after surgery. Another patient with a complete sensory loss after surgery was repetitively tested within 453 days after primary surgery (dental implant) and subsequent surgical reconstruction of the inferior alveolar nerve by autologous graft. RESULTS: Older subjects were significantly less sensitive than younger subjects for thermal parameters. Thermal detection thresholds in infraorbital and mental regions showed higher sensitivity in women. Sensitivity to thermal stimulation was higher in the infraorbital region than in the mental and lingual regions. QST monitored somatosensory deficits and recovery of inferior alveolar nerve functions in all patients. CONCLUSIONS: Age, gender, and anatomic region affect various QST parameters. QST might be useful in the diagnosis of inferior alveolar nerve disorders in patients. In dentistry, the monitoring of afferent nerve fiber functions by QST might support decisions on further interventions.


Assuntos
Traumatismos dos Nervos Cranianos/diagnóstico , Implantação Dentária Endo-Óssea/efeitos adversos , Exame Neurológico/métodos , Parestesia/diagnóstico , Extração Dentária/efeitos adversos , Traumatismos do Nervo Trigêmeo , Nervo Trigêmeo/fisiopatologia , Adulto , Fatores Etários , Análise de Variância , Estudos de Casos e Controles , Traumatismos dos Nervos Cranianos/etiologia , Feminino , Humanos , Masculino , Nervo Mandibular/fisiopatologia , Pessoa de Meia-Idade , Órbita/inervação , Parestesia/etiologia , Recuperação de Função Fisiológica , Valores de Referência , Limiar Sensorial , Fatores Sexuais , Estatísticas não Paramétricas , Adulto Jovem
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