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1.
Dev Cogn Neurosci ; 39: 100703, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31487608

RESUMO

Preterm birth is a significant risk factor for a range of long-term health problems and developmental disabilities. Though touch plays a central role in many perinatal care strategies, the neurobiological basis of these approaches is seldom considered. C-Tactile afferents (CTs) are a class of unmyelinated nerve fibre activated by low force, dynamic touch. Consistent with an interoceptive function, touch specifically targeted to activate CTs activates posterior insular cortex and has been reported to reduce autonomic arousal. The present study compared the effect of 5 min of CT optimal velocity stroking touch to 5 min of static touch on the heart-rate and oxygen saturation levels of preterm infants between 28- & 37-weeks gestational age. CT touch produced a significant decrease in infants' heart-rates and increase in their blood oxygenation levels, which sustained throughout a 5-min post-touch period. In contrast, there was no significant change in heart-rate or blood oxygenation levels of infants receiving static touch. These findings provide support for the hypothesis that CTs signal the affective quality of nurturing touch, providing a neurobiological substrate for the apparent beneficial effects of neonatal tactile interventions and offering insight for their optimisation.


Assuntos
Nível de Alerta/fisiologia , Recém-Nascido Prematuro/fisiologia , Fibras Nervosas Amielínicas/fisiologia , Neurônios Aferentes/fisiologia , Percepção do Tato/fisiologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro/psicologia , Masculino , Distribuição Aleatória , Tato/fisiologia
2.
Muscle Nerve ; 60(5): 575-579, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31443127

RESUMO

BACKGROUND: Myotonic dystrophy type 1 (DM1) is a multisystem disorder affecting the peripheral nervous system. However, studies evaluating somatic small fiber sensory nerve function, which may contribute to pain in DM1, are lacking. METHODS: Using quantitative sensory testing of the hand and foot, we evaluated Aδ and C-fiber function. Of 20 adult DM1 patients recruited, 16 were analyzed. Their results were compared with those of 32 age- and sex-matched controls. RESULTS: No DM1 patient had diabetes mellitus or clinical evidence of small fiber neuropathy. In DM1, hand (P < .01) and foot (P = 0.02) warm detection thresholds were higher than those of controls. Cool detection thresholds were lower in the foot (P < .001). CONCLUSIONS: Subclinical small sensory fiber dysfunction occurs in DM1 patients without large fiber neuropathy. Further research with other modalities is required to characterize these disturbances as disease modifying therapies are developed.


Assuntos
Distrofia Miotônica/fisiopatologia , Fibras Nervosas Mielinizadas/fisiologia , Fibras Nervosas Amielínicas/fisiologia , Limiar Sensorial , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Pé/inervação , Mãos/inervação , Humanos , Masculino , Pessoa de Meia-Idade , Condução Nervosa , Sensação Térmica/fisiologia , Adulto Jovem
3.
Muscle Nerve ; 60(4): 367-375, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31107560

RESUMO

INTRODUCTION: Topical application of lidocaine-and-prilocaine (LP) cream attenuates the functionality of small cutaneous nerve fibers. The aim of this human study was to measure the underlying excitability modulation of small cutaneous nerve fibers using a novel and fast perception threshold tracking (PTT) technique. METHODS: Small sensory fibers were selectively blocked by 120-minute topical application of LP and confirmed by quantitative sensory testing. Excitability changes of small (activated by a specially designed pin electrode) and large (patch electrode) nerve fibers were assessed as the strength-duration relation and threshold electrotonus. RESULTS: The excitability assessed by the strength-duration relation and threshold electrotonus was significantly modulated for the small afferents (P < 0.05, Wilcoxon's test) but not the large afferents. DISCUSSION: This novel PTT technique was able to assess inhibition of membrane properties of small cutaneous fibers, suggesting the usefulness of the technique as a diagnostic method for assessing impairment of small fibers, as seen in many types of polyneuropathies.


Assuntos
Anestésicos Locais/farmacologia , Combinação Lidocaína e Prilocaína/farmacologia , Fibras Nervosas Mielinizadas/efeitos dos fármacos , Limiar Sensorial/efeitos dos fármacos , Neuropatia de Pequenas Fibras/diagnóstico , Administração Cutânea , Adulto , Estudos Cross-Over , Método Duplo-Cego , Estimulação Elétrica , Eletrodiagnóstico , Feminino , Voluntários Saudáveis , Humanos , Masculino , Fibras Nervosas Mielinizadas/fisiologia , Fibras Nervosas Amielínicas/efeitos dos fármacos , Fibras Nervosas Amielínicas/fisiologia , Limiar Sensorial/fisiologia , Adulto Jovem
4.
BMJ ; 365: l1108, 2019 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-31068323

RESUMO

Sensory polyneuropathies, which are caused by dysfunction of peripheral sensory nerve fibers, are a heterogeneous group of disorders that range from the common diabetic neuropathy to the rare sensory neuronopathies. The presenting symptoms, acuity, time course, severity, and subsequent morbidity vary and depend on the type of fiber that is affected and the underlying cause. Damage to small thinly myelinated and unmyelinated nerve fibers results in neuropathic pain, whereas damage to large myelinated sensory afferents results in proprioceptive deficits and ataxia. The causes of these disorders are diverse and include metabolic, toxic, infectious, inflammatory, autoimmune, and genetic conditions. Idiopathic sensory polyneuropathies are common although they should be considered a diagnosis of exclusion. The diagnostic evaluation involves electrophysiologic testing including nerve conduction studies, histopathologic analysis of nerve tissue, serum studies, and sometimes autonomic testing and cerebrospinal fluid analysis. The treatment of these diseases depends on the underlying cause and may include immunotherapy, mitigation of risk factors, symptomatic treatment, and gene therapy, such as the recently developed RNA interference and antisense oligonucleotide therapies for transthyretin familial amyloid polyneuropathy. Many of these disorders have no directed treatment, in which case management remains symptomatic and supportive. More research is needed into the underlying pathophysiology of nerve damage in these polyneuropathies to guide advances in treatment.


Assuntos
Terapias Complementares/métodos , Terapia Genética/métodos , Imunoterapia/métodos , Exame Neurológico/métodos , Polineuropatias/diagnóstico , Humanos , Metanálise como Assunto , Fibras Nervosas Mielinizadas/fisiologia , Fibras Nervosas Amielínicas/fisiologia , Estudos Observacionais como Assunto , Polineuropatias/fisiopatologia , Polineuropatias/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Comportamento de Redução do Risco , Limiar Sensorial/fisiologia
5.
J Vis Exp ; (145)2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30933066

RESUMO

"Affective" touch is believed to be processed in a manner distinct from discriminatory touch and to involve activation of C-tactile (CT) afferent fibers. Touch that optimally activates CT fibers is consistently rated as hedonically pleasant. Patient groups with impaired social-emotional functioning also show disordered affective touch ratings. However, relying on self-reported ratings of touch has many limitations, including recall bias and communication barriers. Here, we describe a methodological approach to study affective responses to touch via facial electromyography (EMG) that circumvents the reliance on self-report ratings. Facial EMG is an objective, quantitative, and non-invasive method to measure facial muscle activity indicative of affective responses. Responses can be assessed across healthy and patient populations without the need for verbal communication. Here, we provide two separate datasets demonstrating that CT-optimal and non-optimal touch elicit distinct facial muscle reactions. Moreover, facial EMG responses are consistent across stimulus modalities, e.g. tactile (experienced touch) and visual (observed touch). Finally, the temporal resolution of facial EMG can detect responses on timescales that supersede that of verbal reporting. Together, our data suggest that facial EMG is a suitable methodology for use in affective tactile research that can be used to supplement, or in some cases, supplant, existing measures.


Assuntos
Eletromiografia , Músculos Faciais/fisiologia , Tato/fisiologia , Emoções/fisiologia , Face/fisiologia , Feminino , Humanos , Fibras Nervosas Amielínicas/fisiologia , Neurônios Aferentes/fisiologia , Estimulação Física , Análise e Desempenho de Tarefas , Percepção do Tato/fisiologia
6.
Dev Cogn Neurosci ; 36: 100639, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30903992

RESUMO

The evaluation of interpersonal touch is heavily influenced by its source. For example, a gentle stroke from a loved one is generally more pleasant than the same tactile stimulation from a complete stranger. Our study tested the early ontogenetic roots of humans' sensitivity to the source of interpersonal touch. We measured the heart rate of three groups of nine-month-olds while their legs were stroked with a brush. The participants were stroked at a different speed in each group (0.3 cm/s, 3 cm/s, 30 cm/s). Depending on the Identity condition (stranger vs. parent), the person who acted as if she was stroking the infant's leg was either an unfamiliar experimenter or the participant's caregiver. In fact, the stimulation was always delivered by a second experimenter blind to the Identity condition. Infants' heart rate decreased more in reaction to strokes when their caregiver rather than a stranger acted as the source of the touch. This effect was found only for tactile stimulations whose velocity (3 cm/s) is known to elicit maximal mean firing rates in a class of afferents named C-tactile fibers (CTs). Thus, the infants' reaction to touch is modulated not just by its mechanical properties but also by its social source.


Assuntos
Emoções/fisiologia , Fibras Nervosas Amielínicas/fisiologia , Percepção do Tato/fisiologia , Tato/fisiologia , Feminino , Humanos , Lactente , Masculino , Adulto Jovem
7.
Neuroscience ; 404: 499-509, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30826524

RESUMO

Under pathological conditions, acupoint sensitization is the phenomenon of acupoints transforming from the stable state to the dynamic state. Evidences suggest that hyperpolarization-activated current (Ih), conducted by the hyperpolarization-activated/cyclic nucleotide-gated (HCN) channel, greatly contributes to the peripheral and central sensitization. However, the role of the Ih current in acupoint sensitization has not been explained. In the present study, changes in excitability, Ih density and the HCN channel of dorsal root ganglion (DRG) nociceptive neurons were examined in the later phase of knee osteoarthritis (KOA) rats. To investigate the neuronal specificity of acupoint sensitization, retrograde dyes were injected into the acupoints ST35 and GB37. The results showed that acupoint sensitization occurred in bilateral ST35 but not GB37 acupoints. The excitability and Ih density of C- but not Aδ-type neurons innervating ST35 acupoint increased in bilateral L5 DRG of acupoint sensitized rats than that of sham rats. No obvious changes were found in the excitability or Ih density of C- and Aδ-type neurons innervating the GB37 acupoint in the bilateral L5 DRG. HCN channel subtype 2 (HCN2) expression levels significantly increased after acupoint sensitization. Furthermore, ZD7288, an HCN current (Ih) blocker, attenuated the acupoint sensitization of the ST35 acupoint. Taken together, our findings suggest that the increased excitability of C- but not Aδ-type neurons and the upregulation of Ih/HCN2 channels contribute to the formation of acupoint sensitization.


Assuntos
Pontos de Acupuntura , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/fisiologia , Fibras Nervosas Mielinizadas/fisiologia , Fibras Nervosas Amielínicas/fisiologia , Neurônios/fisiologia , Osteoartrite do Joelho/terapia , Animais , Masculino , Osteoartrite do Joelho/fisiopatologia , Ratos , Ratos Sprague-Dawley
8.
Eur J Pharmacol ; 849: 154-159, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30716310

RESUMO

Previously, we showed that the synthetic nitroderivative trans-4-methyl-ß-nitrostyrene (T4MeN) induced vasorelaxant effects in rat isolated aortic rings. Here, we investigated the mechanisms underlying the cardiovascular effects of T4MeN in normotensive rats. In pentobarbital-anesthetized rats, intravenous (i.v.) injection of T4MeN (0.03-0.5 mg/kg) induced a rapid (onset time of 1-2 s) and dose-dependent bradycardia and hypotension. These cardiovascular responses to T4MeN were abolished by bilateral cervical vagotomy or selective blockade of neural conduction of vagal C-fiber afferents by perineural treatment of both cervical vagus nerves with capsaicin. Hypotension and bradycardia were also recorded when T4MeN was directly injected in the right, but not into the left ventricle. Furthermore, they were significantly reduced by i.v. pretreatment with capsazepine but remained unaltered by ondansetron or suramin. In conscious rats, the dose-dependent hypotension and bradycardia evoked by T4MeN were abolished by i.v. methylatropine pretreatment. In conclusion, bradycardiac and depressor responses induced by T4MeN has a vago-vagal reflex origin resulting from the vagal pulmonary afferents stimulation. The transduction mechanism seems to involve the activation of vanilloid TRPV1, but not purinergic (P2X) or 5-HT3 receptors located on vagal pulmonary sensory nerves.


Assuntos
Bradicardia/induzido quimicamente , Pulmão/inervação , Fibras Nervosas Amielínicas/efeitos dos fármacos , Reflexo/efeitos dos fármacos , Estirenos/farmacologia , Canais de Cátion TRPV/metabolismo , Nervo Vago/efeitos dos fármacos , Animais , Bradicardia/metabolismo , Bradicardia/fisiopatologia , Masculino , Fibras Nervosas Amielínicas/metabolismo , Fibras Nervosas Amielínicas/fisiologia , Ratos , Ratos Wistar
9.
J Neurophysiol ; 121(5): 1591-1608, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30625007

RESUMO

The monosynaptic stretch reflex (MSR) plays an important role in feedback control of movement and posture but can also lead to unstable oscillations associated with tremor and clonus, especially when increased with spinal cord injury (SCI). To control the MSR and clonus after SCI, we examined how serotonin regulates the MSR in the sacrocaudal spinal cord of rats with and without a chronic spinal transection. In chronic spinal rats, numerous 5-HT receptor agonists, including zolmitriptan, methylergonovine, and 5-HT, inhibited the MSR with a potency highly correlated to their binding affinity to 5-HT1D receptors and not other 5-HT receptors. Selective 5-HT1D receptor antagonists blocked this agonist-induced inhibition, although antagonists alone had no action, indicating a lack of endogenous or constitutive receptor activity. In normal uninjured rats, the MSR was likewise inhibited by 5-HT, but at much higher doses, indicating a supersensitivity after SCI. This supersensitivity resulted from the loss of the serotonin transporter SERT with spinal transection, because normal and injured rats were equally sensitive to 5-HT after SERT was blocked or to agonists not transported by SERT (zolmitriptan). Immunolabeling revealed that the 5-HT1D receptor was confined to superficial lamina of the dorsal horn, colocalized with CGRP-positive C-fibers, and eliminated by dorsal rhizotomy. 5-HT1D receptor labeling was not found on large proprioceptive afferents or α-motoneurons of the MSR. Thus serotonergic inhibition of the MSR acts indirectly by modulating C-fiber activity, opening up new possibilities for modulating reflex function and clonus via pain-related pathways. NEW & NOTEWORTHY Brain stem-derived serotonin potently inhibits afferent transmission in the monosynaptic stretch reflex. We show that serotonin produces this inhibition exclusively via 5-HT1D receptors, and yet these receptors are paradoxically mostly confined to C-fibers. This suggests that serotonin acts by gating of C-fiber activity, which in turn modulates afferent transmission to motoneurons. We also show that the classic supersensitivity to 5-HT after spinal cord injury results from a loss of SERT, and not 5-HT1D receptor plasticity.


Assuntos
Fibras Nervosas Amielínicas/metabolismo , Receptor 5-HT1D de Serotonina/metabolismo , Reflexo de Estiramento , Traumatismos da Medula Espinal/metabolismo , Animais , Feminino , Fibras Nervosas Amielínicas/efeitos dos fármacos , Fibras Nervosas Amielínicas/fisiologia , Ratos , Agonistas do Receptor 5-HT1 de Serotonina/farmacologia , Antagonistas do Receptor 5-HT1 de Serotonina/farmacologia , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Traumatismos da Medula Espinal/fisiopatologia
10.
Am J Physiol Renal Physiol ; 316(4): F703-F711, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30672315

RESUMO

This study in α-chloralose-anesthetized cats revealed a role of hypogastric nerve afferent axons in nociceptive bladder activity induced by bladder irritation using 0.25% acetic acid (AA). In cats with intact hypogastric and pelvic nerves, AA irritation significantly ( P < 0.05) reduced bladder capacity to 45.0 ± 5.7% of the control capacity measured during a saline cystometrogram (CMG). In cats with the hypogastric nerves transected bilaterally, AA irritation also significantly ( P < 0.05) reduced bladder capacity, but the change was significantly smaller (capacity reduced to 71.5 ± 10.6% of saline control, P < 0.05) than that in cats with an intact hypogastric nerve. However, application of hypogastric nerve stimulation (HGNS: 20 Hz, 0.2 ms pulse width) to the central end of the transected nerves at an intensity (16 V) strong enough to activate C-fiber afferent axons facilitated the effect of AA irritation and further ( P < 0.05) reduced bladder capacity to 48.4 ± 7.4% of the saline control. This facilitation by HGNS was effective only at selected frequencies (1, 20, and 30 Hz) when the stimulation intensity was above the threshold for activating C-fibers. Tramadol (an analgesic agent) at 3 mg/kg iv completely blocked the nociceptive bladder activity and eliminated the facilitation by HGNS. HGNS did not alter non-nociceptive bladder activity induced by saline distention of the bladder. These results indicate that sympathetic afferents in the hypogastric nerve play an important role in the facilitation of the nociceptive bladder activity induced by bladder irritation that activates the silent C-fibers in the pelvic nerve.


Assuntos
Neurônios Aferentes/fisiologia , Nociceptividade/fisiologia , Sistema Nervoso Simpático/fisiologia , Bexiga Urinária/fisiologia , Ácido Acético , Analgésicos Opioides/farmacologia , Animais , Axônios/fisiologia , Gatos , Estimulação Elétrica , Feminino , Masculino , Fibras Nervosas Amielínicas/fisiologia , Neurônios Aferentes/efeitos dos fármacos , Nociceptividade/efeitos dos fármacos , Sistema Nervoso Simpático/efeitos dos fármacos , Tramadol/farmacologia
11.
Ann Allergy Asthma Immunol ; 123(2): 158-165, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30685562

RESUMO

OBJECTIVE: Chronic itch can be a debilitating, unrelenting symptom. Over the years, we have advanced our knowledge about immune-mediated itch (eg, atopic dermatitis) and have developed several treatments targeting these immune pathways. Chronic itch that is noninflammatory in nature is more elusive. However, we have gained some understanding of the neural component mediating itch and have made progress in treating this challenging symptom. DATA SOURCES: A comprehensive literature search was conducted, and data and literature were reviewed on the topics of chronic itch, its pathophysiology, and nonimmunological treatments for chronic itch that work on the nerves. STUDY SELECTIONS: Basic science papers, review articles, case reports, and clinical trial data were considered. RESULTS: A variety of topical and systemic therapies targeting the nerves have shown effectiveness in treating patients with chronic itch of different types. CONCLUSION: Treating chronic itch may be challenging, but an arsenal of treatments are available and many are on the horizon as we expand our knowledge of mechanisms of itch and the neural receptors involved.


Assuntos
Analgésicos/uso terapêutico , Antipruriginosos/uso terapêutico , Dermatite Atópica/terapia , Prurido/tratamento farmacológico , Humanos , Fibras Nervosas Amielínicas/fisiologia , Células Receptoras Sensoriais/fisiologia
12.
Biol Psychol ; 140: 55-63, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30468895

RESUMO

Caress-like touch is thought to rely on C-tactile (CT) fiber signaling. Here, the arousing and emotional effects of CT-optimal touch were assessed via participants' skin conductance level (SCL), facial electromyography (EMG) responses and subjective ratings of pleasantness and intensity. Temporal facial EMG analysis was based on the conduction velocity of CT-fibers. 45 healthy participants received CT-optimal touch, control touch and visual control input during 2-minute trials. CT optimal touch was significantly more pleasant and intense than control touch. In the initial 700 ms of stimulation there was no difference in facial EMG responses to touch. Between 700 and 6300 ms there was a significant reduction of corrugator activity in response to CT optimal touch only, possibly reflecting the affective value of CT optimal touch. Based on the temporal dynamics of the reduced corrugator activity, we suggest that CT fibers are involved in mediating a reduction in corrugator activity.


Assuntos
Emoções/fisiologia , Resposta Galvânica da Pele/fisiologia , Fibras Nervosas Amielínicas/fisiologia , Percepção do Tato/fisiologia , Tato/fisiologia , Adulto , Eletromiografia , Face/fisiologia , Feminino , Voluntários Saudáveis , Humanos , Masculino , Estimulação Física/métodos
13.
Low Urin Tract Symptoms ; 11(2): O21-O27, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29105998

RESUMO

OBJECTIVE: The aim of the present study was to investigate associations between urethral sensation and urge urinary incontinence (UUI) in patients with and without detrusor overactivity (DO). METHODS: The medical records of 80 consecutive patients who underwent filling cystometry and urethral current perception threshold (CPT) tests were examined retrospectively. Following the exclusion of 4 patients not eligible for analysis, patients were classified into neurogenic DO, idiopathic DO, or DO-negative groups based on neurological and cystometric findings (n = 30, 12, and 34, respectively). Eleven DO-negative patients were defined as normal controls on cystometrograms (CMG) using the following exclusion criteria: bladder compliance <12.5 mL/cmH2 O, volume >275 mL at first filling sensation, and comorbidities possibly affecting lower urinary tract function. Thus, 53 patients were finally included in the study. Proximal urethral CPT was evaluated with intraurethral square-wave stimulation at 3 Hz to activate C-fiber afferents. RESULTS: Median CPT was higher in neurogenic and idiopathic DO than in the normal CMG group (11.3 and 9.0 vs. 2.8 mA, respectively; P < .05), as well as in patients with UUI (n = 19) compared with non-UUI patients (n = 34; 12.5 vs. 5.4 mA, respectively; P < .05). The proportion of UUI patients was significantly greater in the DO-positive groups than in the normal CMG group (P < .05). CPTs were not associated with bladder capacity at the first filling sensation (r = 0.11). CONCLUSION: Hyposensitive C-fibers of the proximal urethra may contribute to the development of urodynamic DO as well as UUI in patients complaining of lower urinary tract symptoms.


Assuntos
Fibras Nervosas Amielínicas/fisiologia , Uretra/inervação , Bexiga Urinária Hiperativa/complicações , Incontinência Urinária de Urgência/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Uretra/fisiopatologia , Bexiga Urinária Hiperativa/fisiopatologia , Incontinência Urinária de Urgência/fisiopatologia , Urodinâmica , Adulto Jovem
14.
IEEE Trans Biomed Eng ; 66(2): 471-484, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29993457

RESUMO

OBJECTIVE: Currently, there is no imaging method that is able to distinguish the functional activity inside nerves. Such a method would be essential for understanding peripheral nerve physiology and would allow precise neuromodulation of organs these nerves supply. Electrical impedance tomography (EIT) is a method that produces images of electrical impedance change (dZ) of an object by injecting alternating current and recording surface voltages. It has been shown to be able to image fast activity in the brain and large peripheral nerves. To image inside small autonomic nerves, mostly containing unmyelinated fibers, it is necessary to maximize SNR and optimize the EIT parameters. An accurate model of the nerve is required to identify these optimal parameters as well as to validate data obtained in the experiments. METHODS: In this study, we developed two three-dimensional models of unmyelinated fibers: Hodgkin-Huxley (HH) squid giant axon (single and multiple) and mammalian C-nociceptor. A coupling feedback system was incorporated into the models to simulate direct and alternating current application and simultaneously record external field during action potential propagation. RESULTS: Parameters of the developed models were varied to study their influence on the recorded impedance changes; the optimal parameters were identified. The negative dZ was found to monotonically decrease with frequency for both HH and C fiber models, in accordance with the experimental data. CONCLUSION AND SIGNIFICANCE: The accurate realistic model of unmyelinated nerve allows the optimization of EIT parameters and matches literature and experimental results.


Assuntos
Impedância Elétrica , Modelos Neurológicos , Fibras Nervosas Amielínicas/fisiologia , Tomografia/métodos , Animais , Braquiúros/fisiologia , Análise de Elementos Finitos , Processamento de Sinais Assistido por Computador
15.
Curr Biol ; 28(24): R1380-R1381, 2018 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-30562526

RESUMO

A subclass of C fibre sensory neurons found in hairy skin are activated by gentle touch [1] and respond optimally to stroking at ∼1-10 cm/s, serving a protective function by promoting affiliative behaviours. In adult humans, stimulation of these C-tactile (CT) afferents is pleasant, and can reduce pain perception [2]. Touch-based techniques, such as infant massage and kangaroo care, are designed to comfort infants during procedures, and a modest reduction in pain-related behavioural and physiological responses has been observed in some studies [3]. Here, we investigated whether touch can reduce noxious-evoked brain activity. We demonstrate that stroking (at 3 cm/s) prior to an experimental noxious stimulus or clinical heel lance can attenuate noxious-evoked brain activity in infants. CT fibres may represent a biological target for non-pharmacological interventions that modulate pain in early life.


Assuntos
Encéfalo/fisiologia , Fibras Nervosas Amielínicas/fisiologia , Células Receptoras Sensoriais/fisiologia , Percepção do Tato/fisiologia , Tato/fisiologia , Eletroencefalografia , Feminino , Cabelo , Humanos , Recém-Nascido , Masculino , Pele/inervação , Fenômenos Fisiológicos da Pele
16.
Sci Rep ; 8(1): 14967, 2018 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-30297735

RESUMO

High blood pressure (BP) is a highly controllable risk factor for cardiovascular diseases; however, awareness of this condition and the rates of controlled hypertension are low. Experimental animal studies have shown that stimulation of the median nerve or PC6 acupoint over the wrist has effects on cardiovascular activities, including reductions in systolic and diastolic BPs. A proof-of-concept study was conducted in humans to investigate whether stimulation of median nerve near PC6 acupoint decreased high BP, identify the optimal stimulation parameters for the BP-lowering effects of median nerve stimulation, and determine the specific peripheral nerves or types of afferent fibers mediating the BP-lowering effects. Median nerve stimulation was carried out bilaterally or unilaterally with different stimulation parameters, and the BP and heart rate were monitored. The afferent mechanisms underlying the effects of median nerve stimulation on hypertension were investigated via microneurography, A-fiber blocking experiments, and localized chemical or electrical stimulation. Bilateral median nerve stimulation at either low or high frequencies produced profound but transient reductions in systolic BP, which were elicited when median nerve stimulation was unilaterally applied at interelectrode distances of 2 and 4 cm. Systolic BP was also reduced by electrical stimulation of the thumb on the palm side. Although microneurographic recordings revealed the excitation of both A- and C-fibers following median nerve stimulation, the median nerve-mediated reductions in BP were not affected by A-fiber blockade, and they were mimicked by the activation of C-fibers with capsaicin. The present results indicate that activation of C-fibers in the median nerve generates BP-lowering effects in humans. Based on our clinical study, an optimized median nerve stimulator was built and combined with a wrist BP monitor for simultaneous BP measurements and median nerve stimulation.


Assuntos
Hipertensão/terapia , Nervo Mediano/fisiopatologia , Fibras Nervosas Amielínicas/fisiologia , Estimulação Elétrica Nervosa Transcutânea/instrumentação , Adulto , Pressão Sanguínea/efeitos dos fármacos , Monitores de Pressão Arterial , Capsaicina/farmacologia , Eletrodos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/fisiopatologia , Masculino , Nervo Mediano/efeitos dos fármacos , Bloqueio Nervoso , Fibras Nervosas Amielínicas/efeitos dos fármacos , Nervo Ulnar/efeitos dos fármacos , Nervo Ulnar/fisiopatologia , Punho
17.
J Neurophysiol ; 120(6): 2834-2846, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30256737

RESUMO

The technique of microneurography-recording neural traffic from nerves in awake humans-has provided us with unrivaled insights into afferent and efferent processes in the peripheral nervous system for over 50 years. We review the use of microneurography to study single C-fiber afferents and provide an overview of the knowledge gained, with views to future investigations. C-fibers have slowly conducting, thin-diameter, unmyelinated axons and make up the majority of the fibers in peripheral nerves (~80%). With the use of microneurography in humans, C-fiber afferents have been differentiated into discrete subclasses that encode specific qualities of stimuli on the skin, and their functional roles have been investigated. Afferent somatosensory information provided by C-fibers underpins various positive and negative affective sensations from the periphery, including mechanical, thermal, and chemical pain (C-nociceptors), temperature (C-thermoreceptors), and positive affective aspects of touch (C-tactile afferents). Insights from microneurographic investigations have revealed the complexity of the C-fiber system, methods for delineating fundamental C-fiber populations in a translational manner, how C-fiber firing can be used to identify nerve deficits in pathological states, and how the responses from C-fibers may be modified to change sensory percepts, including decreasing pain. Understanding these processes may lead to future medical interventions to diagnose and treat C-fiber dysfunction. NEW & NOTEWORTHY The technique of microneurography allows us to directly investigate the functional roles of single C-fiber afferents in awake human beings. Here we outline and discuss the current field of C-fiber research on this heterogeneous population of afferents in healthy subjects, in pathological states, and from a translational perspective. We cover C-fibers encoding touch, temperature, and pain and provide perspectives on the future of C-fiber microneurography investigations in humans.


Assuntos
Imagem por Ressonância Magnética/métodos , Mecanorreceptores/fisiologia , Fibras Nervosas Amielínicas/fisiologia , Nociceptores/fisiologia , Termorreceptores/fisiologia , Humanos
18.
J Neurosci ; 38(41): 8809-8821, 2018 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-30143577

RESUMO

The dorsal horn of the spinal cord represents the first relay station in the pain pathway where primary nociceptive inputs are modulated by local circuits and by descending signals before being relayed to supraspinal nuclei. To determine whether dopamine can modulate primary nociceptive Aδ- and C-fiber signals, the effects of dopamine were tested on the excitatory postsynaptic currents (EPSCs) recorded from large lamina I neurons and from retrograde-labeled spinoparabrachial lamina I neurons upon stimulation of the L4/L5 dorsal root in horizontal spinal cord slices in vitro Dopamine inhibited the EPSCs in a dose-dependent manner, with substantial inhibition (33%) at 1 µm and maximum inhibition (∼70%) at 10-20 µm Dopamine reduced the frequency of miniature EPSCs recorded from large lamina I neurons, increased the paired pulse depression ratio of paired EPSCs, and induced similar inhibition of EPSCs after dialysis of large lamina I neurons with GDP-ß-S, consistent with actions at presynaptic sites. Pharmacological experiments suggested that the inhibitory effects of dopamine were largely mediated by D4 receptors (53%). Similar inhibition (66%) by dopamine was observed on EPSCs recorded from ipsilateral large lamina I neurons 6 d after injection of complete Freund's adjuvant in the hindpaw, suggesting that dopamine downregulates primary nociceptive inputs to lamina I neurons during chronic inflammatory pain. We propose that presynaptic inhibition of primary nociceptive inputs to lamina I projection neurons is a mechanism whereby dopamine can inhibit incoming noxious stimuli to the dorsal horn of the spinal cord.SIGNIFICANCE STATEMENT Lamina I projection neurons represent the main output for the pain signals from the dorsal horn of the spinal cord to brainstem and thalamic nuclei. We found that dopamine inhibits the nociceptive Aδ- and C-fiber synaptic inputs to lamina I projection neurons via presynaptic actions. Similar inhibitory effects of dopamine on the EPSCs were observed in rats subjected to complete Freund's adjuvant to induce peripheral inflammation, suggesting that dopamine inhibits the synaptic inputs to lamina I neurons in the setting of injury. A better understanding of how primary nociceptive inputs to the dorsal horn of the spinal cord are modulated by descending monoaminergic signals may help in the development of new pharmacological strategies to selectively downregulate the output from lamina I projection neurons.


Assuntos
Dopamina/fisiologia , Inibição Neural , Nociceptividade/fisiologia , Células do Corno Posterior/fisiologia , Terminações Pré-Sinápticas/fisiologia , Animais , Dopamina/administração & dosagem , Potenciais Pós-Sinápticos Excitadores , Feminino , Gânglios Espinais/fisiologia , Masculino , Potenciais Pós-Sinápticos em Miniatura , Fibras Nervosas Mielinizadas/fisiologia , Fibras Nervosas Amielínicas/fisiologia , Ratos Sprague-Dawley , Receptores de Dopamina D3/fisiologia , Receptores de Dopamina D4/fisiologia
19.
Clin Neurophysiol ; 129(11): 2475-2481, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30107982

RESUMO

OBJECTIVE: Microneurography is the only method for recording from single neurons in intact human nerves. It is challenging - requiring technical expertise, investment in specialised equipment and has sparse data yields. METHODS: We assessed whether ultrasound guidance in combination with an 'open access' amplifier and data capture system (Open-Ephys) would simplify and expand the scope of microneurographic recordings in humans. RESULTS: In 32 healthy consenting volunteers, ultrasound-guidance improved success rates for obtaining cutaneous C-fibres and reduced "Skin to Nerve" times from 28.5 min to 4.5 min for recordings of the peroneal nerve (P < 0.0001). We illustrate the potential utility of ultrasound-guided microneurography for difficult to access nerves with phrenic nerve recording during a Valsalva manoeuvre. We show that Open Ephys is a viable alternative to commercially available recording systems and offers advantages in terms of cost and software customisability. CONCLUSIONS: Ultrasound guidance for microneurography with Open Ephys facilitates cutaneous C nociceptor recordings and allows recordings to be made from nerves previously considered inaccessible. SIGNIFICANCE: We anticipate that the adoption of these techniques will improve microneurography experimental efficiency, adds an important visual learning aid and increases the generalisability of the approach.


Assuntos
Eletrofisiologia/métodos , Fibras Nervosas Amielínicas/fisiologia , Condução Nervosa , Nervo Frênico/fisiologia , Ultrassonografia/métodos , Adulto , Eletrofisiologia/normas , Humanos , Masculino , Pessoa de Meia-Idade , Nervo Frênico/citologia
20.
J Physiol ; 596(18): 4443-4455, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29992559

RESUMO

KEY POINTS: A recent animal study showed that high frequency electrical stimulation (HFS) of C-fibres induces a gliogenic heterosynaptic long-term potentiation at the spinal cord that is hypothesized to mediate secondary hyperalgesia in humans. Here this hypothesis was tested by predominantly activating C-fibre nociceptors in the area of secondary mechanical hyperalgesia induced by HFS in humans. It is shown that heat perception elicited by stimuli predominantly activating C-fibre nociceptors is greater, as compared to the control site, after HFS in the area of secondary mechanical hyperalgesia. This is the first study that confirms in humans the involvement of C-fibre nociceptors in the changes in heat sensitivity in the area of secondary mechanical hyperalgesia induced by HFS. ABSTRACT: It has recently been shown that high frequency electrical stimulation (HFS) of C-fibres induces a gliogenic heterosynaptic long-term potentiation (LTP) at the spinal cord in animals, which has been hypothesized to be the underlying mechanism of secondary hyperalgesia in humans. Here we tested this hypothesis using a method to predominantly activate quickly responding C-fibre nociceptors in the area of secondary hyperalgesia induced by HFS in humans. HFS was delivered to one of the two volar forearms in 18 healthy volunteers. Before, 20 min and 45 min after HFS, short-lasting (10 ms) high-intensity CO2 laser heat stimuli delivered to a very small area of the skin (0.15 mm2 ) were applied to the area of increased mechanical pinprick sensitivity at the HFS-treated arm and the homologous area of the contralateral control arm. During heat stimulation the electroencephalogram, reaction times and intensity of perception (numerical rating scale 0-100) were measured. After HFS, we observed a greater heat sensitivity, an enhancement in the number of detected trials, faster reaction times and an enhancement of the N2 wave of C-fibre laser-evoked potentials at the HFS-treated arm compared to the control arm. This is the first study that confirms in humans the involvement of C-fibre nociceptors in enhanced heat sensitivity in the area of secondary mechanical hyperalgesia induced by HFS.


Assuntos
Hiperalgesia/fisiopatologia , Fibras Nervosas Amielínicas/fisiologia , Nociceptividade , Nociceptores/fisiologia , Adulto , Feminino , Temperatura Alta , Humanos , Potenciais Evocados por Laser , Masculino
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