RESUMEN
Cocaine-dependent (CD) individuals demonstrate significant anxiety and dysphoria during withdrawal, a negative emotional state that may perpetuate drug seeking and consumption. An extensive body of work has focused on characterizing reward circuit dysfunction, but relatively little is known about the pain circuit during cocaine withdrawal. In an earlier study, we highlighted how cue-elicited functional connectivity between the periaqueductal gray (PAG), a subcortical hub of the pain circuit, and ventromedial prefrontal cortex supports tonic craving in recently abstinent CD. The functional organization of the brain can be characterized by intrinsic connectivities, and it is highly likely that the resting state functional connectivity (rsFC) of the PAG may also be altered in association with cocaine use variables. Here, we examined this issue in 52 CD and 52 healthy control (HC) participants. Imaging data were processed with published routines, and the findings were evaluated with a corrected threshold. In a covariance analysis, CD as compared with HC showed higher PAG rsFC with the hypothalamus, dorsomedial prefrontal, and inferior parietal cortices. Further, these connectivities were correlated negatively with tonic cocaine craving and recent cocaine use, respectively. Higher hypothalamic and frontoparietal rsFC with the PAG may reflect a compensatory process to regulate craving and compulsive drug use. The findings provide additional evidence in humans implicating the PAG circuit and may help research of the role of negative reinforcement in sustaining habitual drug use in cocaine addiction.
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Trastornos Relacionados con Cocaína/fisiopatología , Hipotálamo/fisiopatología , Sustancia Gris Periacueductal/fisiopatología , Corteza Prefrontal/fisiopatología , Adulto , Encéfalo/fisiopatología , Mapeo Encefálico , Ansia , Señales (Psicología) , Comportamiento de Búsqueda de Drogas , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Lóbulo Parietal/fisiopatología , Recompensa , Síndrome de Abstinencia a Sustancias/fisiopatologíaRESUMEN
Postherpetic Neuralgia (PHN), develops after the resolution of the herpes zoster mucocutaneous eruption, is a debilitating chronic pain. However, there is a lack of knowledge regarding the underlying mechanisms associated with ascending and descending pain modulations in PHN patients. Here, we combined psychophysics with structural and functional magnetic resonance imaging (MRI) techniques to investigate the brain alternations in PHN patients. Psychophysical tests showed that compared with healthy controls, PHN patients had increased state and trait anxiety and depression. Structural MRI data indicated that PHN patients had significantly smaller gray matter volumes of the thalamus and amygdala than healthy controls, and the thalamus volume was negatively correlated with pain intensity (assessed using the Short-form of the McGill pain questionnaire) in PHN patients. When the thalamus and periaqueductal gray matter (PAG) were used as the seeds, resting-state functional MRI data revealed abnormal patterns of functional connectivity within ascending and descending pain pathways in PHN patients, e.g., increased functional connectivity between the thalamus and somatosensory cortices and decreased functional connectivity between the PAG and frontal cortices. In addition, subjective ratings of both Present Pain Index (PPI) and Beck-Depression Inventory (BDI) were negatively correlated with the strength of functional connectivity between the PAG and primary somatosensory cortex (SI), and importantly, the effect of BDI on PPI was mediated by the PAG-SI functional connectivity. Overall, our results provided evidence suggesting deficits in ascending and descending pain modulation pathways, which were highly associated with the intensity of chronic pain and its emotional comorbidities in PHN patients. Therefore, our study deepened our understanding of the pathogenesis of PHN, which would be helpful in determining the optimized treatment for the patients.
Asunto(s)
Amígdala del Cerebelo , Corteza Cerebral , Conectoma , Sustancia Gris , Imagen por Resonancia Magnética , Red Nerviosa , Neuralgia Posherpética/fisiopatología , Sustancia Gris Periacueductal , Tálamo , Anciano , Amígdala del Cerebelo/diagnóstico por imagen , Amígdala del Cerebelo/patología , Amígdala del Cerebelo/fisiopatología , Ansiedad/fisiopatología , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Corteza Cerebral/fisiopatología , Depresión/fisiopatología , Femenino , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Sustancia Gris/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/patología , Red Nerviosa/fisiopatología , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Neuralgia Posherpética/diagnóstico por imagen , Neuralgia Posherpética/patología , Sustancia Gris Periacueductal/diagnóstico por imagen , Sustancia Gris Periacueductal/patología , Sustancia Gris Periacueductal/fisiopatología , Tálamo/diagnóstico por imagen , Tálamo/patología , Tálamo/fisiopatologíaRESUMEN
Irritable bowel syndrome (IBS) is a disorder involving dysfunctional brain-gut interactions characterized by chronic recurrent abdominal pain, altered bowel habits, and negative emotion. Previous studies have linked the habenula to the pathophysiology of negative emotion and pain. However, no studies to date have investigated habenular function in IBS patients. In this study, we investigated the resting-state functional connectivity (rsFC) and effective connectivity of the habenula in 34 subjects with IBS and 34 healthy controls and assessed the feasibility of differentiating IBS patients from healthy controls using a machine learning method. Our results showed significantly enhanced rsFC of the habenula-left dorsolateral prefrontal cortex (dlPFC) and habenula-periaqueductal grey (PAG, dorsomedial part), as well as decreased rsFC of the habenula-right thalamus (dorsolateral part), in the IBS patients compared with the healthy controls. Habenula-thalamus rsFC was positively correlated with pain intensity (r = .467, p = .005). Dynamic causal modeling (DCM) revealed significantly decreased effective connectivity from the right habenula to the right thalamus in the IBS patients compared to the healthy controls that was negatively correlated with disease duration (r = -.407, p = .017). In addition, IBS was classified with an accuracy of 71.5% based on the rsFC of the habenula-dlPFC, habenula-thalamus, and habenula-PAG in a support vector machine (SVM), which was further validated in an independent cohort of subjects (N = 44, accuracy = 65.2%, p = .026). Taken together, these findings establish altered habenular rsFC and effective connectivity in IBS, which extends our mechanistic understanding of the habenula's role in IBS.
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Conectoma , Corteza Prefontal Dorsolateral/fisiopatología , Habénula/fisiopatología , Síndrome del Colon Irritable/diagnóstico por imagen , Síndrome del Colon Irritable/fisiopatología , Imagen por Resonancia Magnética , Dolor/fisiopatología , Sustancia Gris Periacueductal/fisiopatología , Máquina de Vectores de Soporte , Tálamo/fisiopatología , Adulto , Estudios Transversales , Corteza Prefontal Dorsolateral/diagnóstico por imagen , Estudios de Factibilidad , Femenino , Habénula/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Dolor/diagnóstico por imagen , Sustancia Gris Periacueductal/diagnóstico por imagen , Tálamo/diagnóstico por imagen , Adulto JovenRESUMEN
AIMS: We compared brain activation patterns between female multiple sclerosis (MS) patients with voiding dysfunction (VD) and those without. We aim to expand current knowledge of supraspinal correlates of voiding initiation within a cohort of female MS patients with and without VD. MATERIALS AND METHODS: Twenty-eight ambulatory female MS patients with stable disease and lower urinary tract dysfunction were recruited for this study. Subjects were divided into group 1, without VD (n = 14), and group 2, with VD (n = 14), defined as postvoid residual urine of ≥40% of maximum cystometric capacity or need for self-catheterization. We recorded brain activity via functional magnetic resonance imaging (fMRI) with simultaneous urodynamic testing. Average fMRI activation maps (the Student t test) were created for both groups, and areas of significant activation were identified (P < .05). A priori regions of interest (ROIs), identified by prior meta-analysis to be involved in voiding, were selected. RESULTS: Group-averaged blood-oxygen level-dependent (BOLD) activation maps demonstrated significant differences between groups 1 and 2 during initiation of voiding with group 2 showing significantly lower levels of activation in all ROIs except for the left cerebellum and right cingulate gyrus. Interestingly, group 2 displayed negative BOLD signals, while group 1 displayed positive signals in the right and left pontine micturition center, right periaqueductal gray, left thalamus, and left cingulate gyrus. The activation map of group 1 was similar to healthy controls. CONCLUSIONS: Our results support the hypothesis that distinct supraspinal activation patterns exist between female MS patients with VD and those without.
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Encéfalo/diagnóstico por imagen , Síntomas del Sistema Urinario Inferior/fisiopatología , Esclerosis Múltiple/diagnóstico por imagen , Vejiga Urinaria Neurogénica/fisiopatología , Trastornos Urinarios/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Encéfalo/fisiopatología , Estudios de Casos y Controles , Cerebelo/diagnóstico por imagen , Cerebelo/fisiopatología , Femenino , Neuroimagen Funcional , Giro del Cíngulo/diagnóstico por imagen , Giro del Cíngulo/fisiopatología , Humanos , Síntomas del Sistema Urinario Inferior/etiología , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/fisiopatología , Sustancia Gris Periacueductal/diagnóstico por imagen , Sustancia Gris Periacueductal/fisiopatología , Puente/diagnóstico por imagen , Puente/fisiopatología , Tálamo/diagnóstico por imagen , Tálamo/fisiopatología , Vejiga Urinaria/fisiopatología , Vejiga Urinaria Neurogénica/etiología , Micción/fisiología , Trastornos Urinarios/etiología , Urodinámica/fisiologíaRESUMEN
Between 1999 and 2014, the prevalence of opioid use disorder (OUD) among pregnant women quadrupled in the USA. The standard treatment for peripartum women with OUD is buprenorphine. However, the maternal behavior neurocircuit that regulates maternal behavior and mother-infant bonding has not been previously studied for human mothers receiving buprenorphine treatment for OUD (BT). Rodent research shows opioid effects on reciprocal inhibition between maternal care and defence maternal brain subsystems: the hypothalamus and periaqueductal gray, respectively. We conducted a longitudinal functional magnetic resonance imaging (fMRI) pilot study in humans to specifically examine resting-state functional connectivity (rs-FC) between the periaqueductal gray and hypothalamus, as well as to explore associations with maternal bonding for BT. We studied 32 mothers who completed fMRI scans at 1 month (T1) and 4 months postpartum (T2), including seven mothers receiving buprenorphine for OUD and 25 non-OUD mothers as a comparison group (CG). The participants underwent a 6-minute resting-state fMRI scan at each time point. We measured potential bonding impairments using the Postpartum Bonding Questionnaire to explore how rs-FC with periaqueductal gray is associated with bonding impairments. Compared to CG, BT mothers differed in periaqueductal gray-dependent rs-FC with the hypothalamus, amygdala, insular cortex and other brain regions at T1, with many of these differences disappearing at T2, suggesting potential therapeutic effects of continuing buprenorphine treatment. In contrast, the "rejection and pathological anger" subscale of the Postpartum Bonding Questionnaire at T1 and T2 was associated with the T1-to-T2 increases in periaqueductal gray-dependent rs-FC with the hypothalamus and amygdala. Preliminary evidence links maternal bonding problems for mothers with OUD early in the postpartum to connectivity between specific care and defence maternal brain circuits, which may be mitigated by buprenorphine treatment. This exploratory study supports a potential mechanism for investigating both the therapeutic benefits and risks of opioids for maternal care and bonding with infants.
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Buprenorfina/uso terapéutico , Hipotálamo/efectos de los fármacos , Hipotálamo/fisiopatología , Antagonistas de Narcóticos/uso terapéutico , Trastornos Relacionados con Opioides/prevención & control , Sustancia Gris Periacueductal/efectos de los fármacos , Sustancia Gris Periacueductal/fisiopatología , Periodo Posparto/fisiología , Adulto , Mapeo Encefálico , Humanos , Imagen por Resonancia Magnética , Relaciones Madre-Hijo , Proyectos Piloto , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: Motor cortex stimulation (MCS) is a neurosurgical technique used to treat patients with refractory neuropathic pain syndromes. MCS activates the periaqueductal gray (PAG) matter, which is one of the major centers of the descending pain inhibitory system. However, the neurochemical mechanisms in the PAG that underlie the analgesic effect of MCS have not yet been described. The main goal of this study was to investigate the neurochemical mechanisms involved in the analgesic effect induced by MCS in neuropathic pain. Specifically, we investigated the release of γ-aminobutyric acid (GABA), glycine, and glutamate in the PAG and performed pharmacological antagonism experiments to validate of our findings. METHODS: Male Wistar rats with surgically induced chronic constriction of the sciatic nerve, along with sham-operated rats and naive rats, were implanted with both unilateral transdural electrodes in the motor cortex and a microdialysis guide cannula in the PAG and subjected to MCS. The MCS was delivered in single 15-minute sessions. Neurotransmitter release was evaluated in the PAG before, during, and after MCS. Quantification of the neurotransmitters GABA, glycine, and glutamate was performed using a high-performance liquid chromatography system. The mechanical nociceptive threshold was evaluated initially, on the 14th day following the surgery, and during the MCS. In another group of neuropathic rats, once the analgesic effect after MCS was confirmed by the mechanical nociceptive test, rats were microinjected with saline or a glycine antagonist (strychnine), a GABA antagonist (bicuculline), or a combination of glycine and GABA antagonists (strychnine+bicuculline) and reevaluated for the mechanical nociceptive threshold during MCS. RESULTS: MCS reversed the hyperalgesia induced by peripheral neuropathy in the rats with chronic sciatic nerve constriction and induced a significant increase in the glycine and GABA levels in the PAG in comparison with the naive and sham-treated rats. The glutamate levels remained stable under all conditions. The antagonism of glycine, GABA, and the combination of glycine and GABA reversed the MCS-induced analgesia. CONCLUSIONS: These results suggest that the neurotransmitters glycine and GABA released in the PAG may be involved in the analgesia induced by cortical stimulation in animals with neuropathic pain. Further investigation of the mechanisms involved in MCS-induced analgesia may contribute to clinical improvements for the treatment of persistent neuropathic pain syndromes.
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Analgesia/métodos , Estimulación Encefálica Profunda , Glicina/fisiología , Corteza Motora/fisiopatología , Neuralgia/terapia , Sustancia Gris Periacueductal/fisiopatología , Ciática/terapia , Ácido gamma-Aminobutírico/fisiología , Animales , Bicuculina/administración & dosificación , Bicuculina/toxicidad , Vías Eferentes/efectos de los fármacos , Vías Eferentes/fisiología , Antagonistas del GABA/administración & dosificación , Antagonistas del GABA/toxicidad , Ácido Glutámico/análisis , Glicina/análisis , Glicina/antagonistas & inhibidores , Glicina/uso terapéutico , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/fisiopatología , Hiperalgesia/terapia , Masculino , Microdiálisis , Microinyecciones , Neuralgia/tratamiento farmacológico , Neuralgia/fisiopatología , Umbral del Dolor , Sustancia Gris Periacueductal/efectos de los fármacos , Ratas , Ratas Wistar , Nervio Ciático/lesiones , Ciática/tratamiento farmacológico , Ciática/fisiopatología , Estricnina/administración & dosificación , Estricnina/toxicidad , Ácido gamma-Aminobutírico/análisis , Ácido gamma-Aminobutírico/uso terapéuticoRESUMEN
OBJECTIVE: Understanding the function of sensory thalamic neural activity is essential for developing and improving interventions for neuropathic pain. However, there is a lack of investigation of the relationship between sensory thalamic oscillations and pain relief in patients with neuropathic pain. This study aims to identify the oscillatory neural characteristics correlated with pain relief induced by deep brain stimulation (DBS), and develop a quantitative model to predict pain relief by integrating characteristic measures of the neural oscillations. APPROACH: Measures of sensory thalamic local field potentials (LFPs) in thirteen patients with neuropathic pain were screened in three dimensional feature space according to the rhythm, balancing, and coupling neural behaviours, and correlated with pain relief. An integrated approach based on principal component analysis (PCA) and multiple regression analysis is proposed to integrate the multiple measures and provide a predictive model. MAIN RESULTS: This study reveals distinct thalamic rhythms of theta, alpha, high beta and high gamma oscillations correlating with pain relief. The balancing and coupling measures between these neural oscillations were also significantly correlated with pain relief. SIGNIFICANCE: The study enriches the series research on the function of thalamic neural oscillations in neuropathic pain and relief, and provides a quantitative approach for predicting pain relief by DBS using thalamic neural oscillations.
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Ondas Encefálicas , Estimulación Encefálica Profunda , Neuralgia/diagnóstico , Neuralgia/fisiopatología , Tálamo/fisiopatología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuralgia/prevención & control , Dimensión del Dolor , Sustancia Gris Periacueductal/fisiopatología , Sustancia Gris Periacueductal/cirugía , Análisis de Componente Principal , Análisis de Regresión , Índice de Severidad de la Enfermedad , Tálamo/cirugíaRESUMEN
The aims of this study were to 1) compare resting state functional connectivity (rs-fc) of the periaqueductal gray (PAG), a key region in the descending pain modulatory system (DPMS) between migraine without aura (MwoA) patients and healthy controls (HC), and 2) investigate how an effective treatment can influence the PAG rs-fc in MwoA patients. One hundred MwoA patients and forty-six matched HC were recruited. Patients were randomized to verum acupuncture, sham acupuncture, and waiting list groups. Resting state fMRI data were collected and seed based functional connectivity analysis was applied. Compared with HC, MwoA patients showed reduced rs-fc between the PAG and rostral anterior cingulate cortex/medial prefrontal cortex (rACC/mPFC), key regions in the DPMS and other pain related brain regions. The reduced rs-fc between the PAG and rACC/mPFC was associated with increased migraine headache intensity at the baseline. After treatments, rs-fc between the PAG and the rACC in MwoA patients significantly increased. The changes of rs-fc among the PAG, rACC and ventral striatum were significantly associated with headache intensity improvement. Impairment of the DPMS is involved in the neural pathophysiology of migraines. Impaired DPMS in migraine patients can be normalized after effective treatment.
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Mapeo Encefálico/métodos , Imagen por Resonancia Magnética/métodos , Migraña sin Aura/terapia , Dolor/fisiopatología , Sustancia Gris Periacueductal/fisiopatología , Terapia por Acupuntura , Adolescente , Adulto , Femenino , Giro del Cíngulo/fisiopatología , Humanos , Masculino , Migraña sin Aura/fisiopatología , Umbral del Dolor , Corteza Prefrontal/fisiopatología , Distribución Aleatoria , Adulto JovenRESUMEN
BACKGROUND: Although the exact mechanism of TENS pain relief is unknown, it is believed that TENS impulses interrupt nociceptive signals at the dorsal horn of the spinal cord. AIMS: To evaluate the hypotheses that during pain caused by noxious stimuli, brain responses, temporal summation and brain functional connectivity are modulated by TENS, and that mechanisms of pain relief by TENS differ between men and women. METHODS: During fMRI scanning, the same noxious stimuli were delivered to each participant in pain-only and pain+TENS conditions. In the pain-only condition, noxious stimuli were presented without TENS. In the pain+TENS condition, participants received noxious stimuli and TENS concurrently. Participants were initially presented with TENS at an intensity that was just below that causing discomfort. TENS intensity was presented in a step-wise fashion to prevent temporal summation from repetitive noxious stimuli. RESULTS: Pain and unpleasantness ratings were significantly higher in the pain-only than the pain+TENS condition. With non-painful TENS, primary and secondary somatosensory and parietal cortices were activated, and temporal summation from repetitive noxious stimuli was prevented. Periaqueductal gray (PAG) and lateral prefrontal cortex functional connectivity was increased by TENS, and modulated by testosterone and cortisol. Women reported greater pain during TENS than men, and showed greater activation in the temporoparietal junction cortex and increased PAG functional connectivity with the orbitofrontal cortex. CONCLUSION: TENS led to pain reduction, probably due to activation of the descending pain-inhibitory pathway, indicating that this TENS method may be applied in clinical practice.
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Corteza Cerebral/fisiopatología , Imagen por Resonancia Magnética/métodos , Evaluación de Resultado en la Atención de Salud/métodos , Manejo del Dolor/métodos , Percepción del Dolor/fisiología , Sustancia Gris Periacueductal/fisiopatología , Estimulación Eléctrica Transcutánea del Nervio/métodos , Adulto , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
BACKGROUND: While electroacupuncture (EA) pretreatment has been found to ameliorate migraine-like symptoms, the underlying mechanisms remain poorly understood. Emerging evidence suggests that the brainstem descending pain modulatory system, comprising the periaqueductal grey (PAG), raphe magnus nucleus (RMg), and trigeminal nucleus caudalis (TNC), may be involved in migraine pathophysiology. We hypothesised that EA would ameliorate migraine-like symptoms via modulation of this descending system. METHODS: We used a conscious rat model of migraine induced by repeated electrical stimulation of the dura. Forty male Sprague-Dawley rats were randomly assigned to one of four groups: an EA group, which received EA at GB20 following dural stimulation; a sham acupuncture (SA) group, which received manual acupuncture at a non-acupuncture point following dural stimulation; a Model group, which received dural stimulation but no acupuncture; and a Control group, which received neither dural stimulation nor acupuncture (electrode implantation only). HomeCageScan was used to measure effects on behaviour, and immunofluorescence staining was used to examine neural activation (c-Fos immunoreactivity) in the PAG, RMg, and TNC. RESULTS: Compared to the Model group, rats in the EA group showed a significant increase in exploratory, locomotor and eating/drinking behaviour (p<0.01) and a significant decrease in freezing-like resting and grooming behaviour (p<0.05). There was a significant increase in the mean number of c-Fos neurons in the PAG, RMg, and TNC in Model versus Control groups (p<0.001); however, this was significantly attenuated by EA treatment (p<0.001). There were no significant differences between the SA and Model groups in behaviour or c-Fos immunoreactivity. CONCLUSIONS: EA pretreatment ameliorates behavioural changes in a rat model of recurrent migraine, possibly via modulation of the brainstem descending pathways.
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Puntos de Acupuntura , Electroacupuntura , Trastornos Migrañosos/terapia , Animales , Modelos Animales de Enfermedad , Ingestión de Alimentos , Humanos , Locomoción , Masculino , Trastornos Migrañosos/fisiopatología , Núcleo Magno del Rafe/fisiopatología , Sustancia Gris Periacueductal/fisiopatología , Ratas , Ratas Sprague-DawleyRESUMEN
Acupuncture, an ancient East Asian therapy, is aimed at rectifying the imbalance within the body caused by disease. Studies evaluating the efficacy of acupuncture with neuroimaging tend to concentrate on brain regions within the pain matrix, associated with acute pain. We, however, focused on the effect of repeated acupuncture treatment specifically on brain regions known to support functions dysregulated in chronic pain disorders. Transition to chronic pain is associated with increased attention to pain, emotional rumination, nociceptive memory and avoidance learning, resulting in brain connectivity changes, specifically affecting the periaqueductal gray (PAG), medial frontal cortex (MFC) and bilateral hippocampus (Hpc). We demonstrate that the PAG-MFC and PAG-Hpc connectivity in patients with chronic pain due to knee osteoarthritis indeed correlates with clinical severity scores and further show that verum acupuncture-induced improvement in pain scores (compared to sham) is related to the modulation of PAG-MFC and PAG-Hpc connectivity in the predicted direction. This study shows that repeated verum acupuncture might act by restoring the balance in the connectivity of the key pain brain regions, altering pain-related attention and memory.
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Terapia por Acupuntura , Dolor Crónico/prevención & control , Dolor Crónico/fisiopatología , Lóbulo Frontal/fisiopatología , Hipocampo/fisiopatología , Osteoartritis de la Rodilla/complicaciones , Sustancia Gris Periacueductal/fisiopatología , Mapeo Encefálico , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Vías Nerviosas/fisiopatología , Dimensión del DolorRESUMEN
Using computerized pupillometry, our previous research established that the autonomic nervous system (ANS) is dysregulated in patients suffering from temporomandibular disorders (TMDs), suggesting a potential role for ANS dysfunction in pain modulation and the etiology of TMD. However, pain modulation hypotheses for TMD are still lacking. The periaqueductal gray (PAG) is involved in the descending modulation of defensive behavior and pain through µ, κ, and δ opioid receptors. Transcutaneous electrical nerve stimulation (TENS) has been extensively used for pain relief, as low-frequency stimulation can activate µ receptors. Our aim was to use pupillometry to evaluate the effect of low-frequency TENS stimulation of µ receptors on opioid descending pathways in TMD patients. In accordance with the Research Diagnostic Criteria for TMD, 18 females with myogenous TMD and 18 matched-controls were enrolled. All subjects underwent subsequent pupillometric evaluations under dark and light conditions before, soon after (end of stimulation) and long after (recovery period) sensorial TENS. The overall statistics derived from the darkness condition revealed no significant differences in pupil size between cases and controls; indeed, TENS stimulation significantly reduced pupil size in both groups. Controls, but not TMD patients, displayed significant differences in pupil size before compared with after TENS. Under light conditions, TMD patients presented a smaller pupil size compared with controls; the pupil size was reduced only in the controls. Pupil size differences were found before and during TENS and before and after TENS in the controls only. Pupillometry revealed that stimulating the descending opioid pathway with low-frequency sensory TENS of the fifth and seventh pairs of cranial nerves affects the peripheral target. The TMD patients exhibited a different pattern of response to TENS stimulation compared with the controls, suggesting that impaired modulation of the descending pain system may be involved in TMD.
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Dolor/metabolismo , Dolor/fisiopatología , Trastornos de la Articulación Temporomandibular/metabolismo , Trastornos de la Articulación Temporomandibular/fisiopatología , Adulto , Sistema Nervioso Autónomo/metabolismo , Sistema Nervioso Autónomo/fisiopatología , Estudios de Casos y Controles , Femenino , Humanos , Manejo del Dolor/métodos , Dimensión del Dolor/métodos , Sustancia Gris Periacueductal/metabolismo , Sustancia Gris Periacueductal/fisiopatología , Receptores Opioides/metabolismo , Estimulación Eléctrica Transcutánea del Nervio/métodosRESUMEN
Deep brain stimulation (DBS) is a neurosurgical intervention the efficacy, safety, and utility of which are established in the treatment of Parkinson's disease. For the treatment of chronic, neuropathic pain refractory to medical therapies, many prospective case series have been reported, but few have published findings from patients treated with current standards of neuroimaging and stimulator technology over the last decade . We summarize the history, science, selection, assessment, surgery, programming, and personal clinical experience of DBS of the ventral posterior thalamus, periventricular/periaqueductal gray matter, and latterly rostral anterior cingulate cortex (Cg24) in 113 patients treated at 2 centers (John Radcliffe, Oxford, UK, and Hospital de São João, Porto, Portugal) over 13 years. Several experienced centers continue DBS for chronic pain, with success in selected patients, in particular those with pain after amputation, brachial plexus injury, stroke, and cephalalgias including anesthesia dolorosa. Other successes include pain after multiple sclerosis and spine injury. Somatotopic coverage during awake surgery is important in our technique, with cingulate DBS under general anesthesia considered for whole or hemibody pain, or after unsuccessful DBS of other targets. Findings discussed from neuroimaging modalities, invasive neurophysiological insights from local field potential recording, and autonomic assessments may translate into improved patient selection and enhanced efficacy, encouraging larger clinical trials.
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Encéfalo/fisiopatología , Estimulación Encefálica Profunda/métodos , Neuralgia/terapia , Estimulación Encefálica Profunda/historia , Historia del Siglo XX , Humanos , Selección de Paciente , Sustancia Gris Periacueductal/fisiopatología , Tálamo/fisiopatologíaRESUMEN
As a complementary medical procedure, acupuncture has a significant impact on the treatment of acute and chronic pain. Though the physiological mechanisms behind this method are still unclear, acupuncture has been claimed to rely also on changes in the central nervous system. Recent functional imaging studies indicate that the so-called default mode network (DMN) which consists of cortical midline structures and lateral parietal regions plays an important role in these processes. This brief overview describes the effects of analgesic acupuncture on the DMN architecture. The stronger interplay between systems dedicated to endogenous analgesia (periaqueductal gray), affective processing (anterior cingulate cortex, amygdala), memory (hippocampus), and self-projective thinking (DMN) following this therapy supports the notion that acupuncture is a mind-body therapy which helps to reintegrate important neural dimensions of inner life and to establish psychophysical pain homeostasis.
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Analgesia por Acupuntura/métodos , Encéfalo/fisiopatología , Imagen por Resonancia Magnética , Red Nerviosa/fisiopatología , Dolor/fisiopatología , Puntos de Acupuntura , Afecto/fisiología , Amígdala del Cerebelo/fisiopatología , Corteza Cerebral/fisiopatología , Giro del Cíngulo/fisiopatología , Hipocampo/fisiopatología , Humanos , Recuerdo Mental/fisiología , Relaciones Metafisicas Mente-Cuerpo/fisiología , Lóbulo Parietal/fisiopatología , Sustancia Gris Periacueductal/fisiopatologíaRESUMEN
Besides the responses to nociceptive stimuli other neural function modes of the brain are necessary to obtain a comprehensive understanding of pain processing in humans. During a resting state without extrinsic stimulation the human brain generates spontaneous low frequency fluctuations of neural activity. This intrinsic activity does not reflect random background noise but is highly organized in several networks. Based on the findings of recent functional imaging studies, the role of these resting state networks in acute and chronic pain is discussed.
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Encéfalo/fisiopatología , Red Nerviosa/fisiopatología , Nociceptores/fisiología , Dolor/fisiopatología , Mapeo Encefálico , Dolor Crónico/fisiopatología , Giro del Cíngulo/fisiopatología , Humanos , Inhibición Neural/fisiología , Umbral del Dolor/fisiología , Sustancia Gris Periacueductal/fisiopatología , Tractos Espinotalámicos/fisiopatología , Tálamo/fisiopatología , Núcleos del Trigémino/fisiopatologíaRESUMEN
Motor cortex stimulation (MCS) has been used to treat patients with neuropathic pain resistant to other therapeutic approaches; however, the mechanisms of pain control by MCS are still not clearly understood. We have demonstrated that MCS increases the nociceptive threshold of naive conscious rats, with opioid participation. In the present study, the effect of transdural MCS on neuropathic pain in rats subjected to chronic constriction injury of the sciatic nerve was investigated. In addition, the pattern of neuronal activation, evaluated by Fos and Zif268 immunolabel, was performed in the spinal cord and brain sites associated with the modulation of persistent pain. MCS reversed the mechanical hyperalgesia and allodynia induced by peripheral neuropathy. After stimulation, Fos immunoreactivity (Fos-IR) decreased in the dorsal horn of the spinal cord and in the ventral posterior lateral and medial nuclei of the thalamus, when compared to animals with neuropathic pain. Furthermore, the MCS increased the Fos-IR in the periaqueductal gray, the anterior cingulate cortex and the central and basolateral amygdaloid nuclei. Zif268 results were similar to those obtained for Fos, although no changes were observed for Zif268 in the anterior cingulate cortex and the central amygdaloid nucleus after MCS. The present findings suggest that MCS reverts neuropathic pain phenomena in rats, mimicking the effect observed in humans, through activation of the limbic and descending pain inhibitory systems. Further investigation of the mechanisms involved in this effect may contribute to the improvement of the clinical treatment of persistent pain.
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Terapia por Estimulación Eléctrica , Hiperalgesia/terapia , Corteza Motora/fisiopatología , Neuralgia/terapia , Neuronas/fisiología , Nervio Ciático/lesiones , Animales , Hiperalgesia/metabolismo , Hiperalgesia/fisiopatología , Masculino , Corteza Motora/metabolismo , Neuralgia/metabolismo , Neuralgia/fisiopatología , Umbral del Dolor/fisiología , Sustancia Gris Periacueductal/metabolismo , Sustancia Gris Periacueductal/fisiopatología , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Ratas Wistar , Resultado del TratamientoRESUMEN
This review develops the hypothesis that co-morbid balance disorders and migraine can be understood as additive effects of processing afferent vestibular and pain information in pre-parabrachial and pre-thalamic pathways, that have consequences on cortical mechanisms influencing perception, interoception and affect. There are remarkable parallel neurochemical phenotypes for inner ear and trigeminal ganglion cells and these afferent channels appear to converge in shared central pathways for vestibular and nociceptive information processing. These pathways share expression of receptors targeted by anti-migraine drugs. New evidence is also presented regarding the distribution of serotonin receptors in the planum semilunatum of the primate cristae ampullaris, which may indicate involvement of inner ear ionic homeostatic mechanisms in audiovestibular symptoms that can accompany migraine.
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Trastornos Migrañosos/fisiopatología , Dolor/fisiopatología , Vértigo/fisiopatología , Vestíbulo del Laberinto/fisiopatología , Vías Aferentes/fisiopatología , Comorbilidad , Homeostasis , Humanos , Hiperacusia/etiología , Hiperacusia/fisiopatología , Trastornos Migrañosos/complicaciones , Trastornos Migrañosos/epidemiología , Modelos Neurológicos , Mareo por Movimiento/fisiopatología , Nociceptores/fisiología , Sustancia Gris Periacueductal/fisiopatología , Fotofobia/etiología , Fotofobia/fisiopatología , Receptores de Serotonina/fisiología , Neuronas Serotoninérgicas/fisiología , Agonistas de Receptores de Serotonina/uso terapéutico , Ganglio Espiral de la Cóclea/fisiopatología , Tálamo/fisiopatología , Ganglio del Trigémino/fisiopatología , Vértigo/epidemiología , Vértigo/etiología , Nervio Vestibular/fisiopatologíaRESUMEN
BACKGROUND: Electroacupuncture (EA) is currently one of the most popular acupuncture modalities. However, the continuous stimulation characteristic of EA treatment presents challenges to the use of conventional functional Magnetic Resonance Imaging (fMRI) approaches for the investigation of neural mechanisms mediating treatment response because of the requirement for brief and intermittent stimuli in event related or block designed task paradigms. A relatively new analysis method, functional connectivity fMRI (fcMRI), has great potential for studying continuous treatment modalities such as EA. In a previous study, we found that, compared with sham acupuncture, EA can significantly reduce Periaqueductal Gray (PAG) activity when subsequently evoked by experimental pain. Given the PAG's important role in mediating acupuncture analgesia, in this study we investigated functional connectivity with the area of the PAG we previously identified and how that connectivity was affected by genuine and sham EA. RESULTS: Forty-eight subjects, who were randomly assigned to receive either genuine or sham EA paired with either a high or low expectancy manipulation, completed the study. Direct comparison of each treatment mode's functional connectivity revealed: significantly greater connectivity between the PAG, left posterior cingulate cortex (PCC), and precuneus for the contrast of genuine minus sham; significantly greater connectivity between the PAG and right anterior insula for the contrast of sham minus genuine; no significant differences in connectivity between different contrasts of the two expectancy levels. CONCLUSIONS: Our findings indicate the intrinsic functional connectivity changes among key brain regions in the pain matrix and default mode network during genuine EA compared with sham EA. We speculate that continuous genuine EA stimulation can modify the coupling of spontaneous activity in brain regions that play a role in modulating pain perception.
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Electroacupuntura/métodos , Imagen por Resonancia Magnética/métodos , Vías Nerviosas/fisiología , Sustancia Gris Periacueductal/fisiología , Analgesia por Acupuntura/métodos , Adulto , Mapeo Encefálico , Femenino , Humanos , Masculino , Percepción del Dolor , Sustancia Gris Periacueductal/fisiopatología , Placebos , Adulto JovenRESUMEN
Current functional neuroimaging studies in headache patients have demonstrated that changes in vascular function are not the primary cause for the pain in migraine. Especially in headache research, functional imaging revealed for the first time important information on the pathophysiology of idiopathic syndromes beyond mere anatomical attribution. Several independent studies have reinforced the crucial role of the brainstem in migraine resulting in primary dysfunction of the endogenous antinociceptive systems, including the periaqueductal grey and the dorsal raphe nucleus (DRN) in the midbrain as well as areas involved in the neuronal regulation of cerebral blood flow (DRN and locus coeruleus). The hypothalamus on the other hand is involved in the fundamental processes leading to the acute attacks of cluster headache. These data have been repeatedly replicated by several groups and led to a new understanding of the pathophysiology of these syndromes and specifically the central role of the brain. The recent studies investigating the structural changes in migraine, chronic tension-type headache and cluster headache are not yet clear in their relevance but raise important questions and promise increasing knowledge of one of the most frequent symptoms in humans.
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Encéfalo/fisiopatología , Imagen de Difusión por Resonancia Magnética , Cefalea/fisiopatología , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Encéfalo/irrigación sanguínea , Mapeo Encefálico , Tronco Encefálico/fisiopatología , Cefalalgia Histamínica/fisiopatología , Depresión de Propagación Cortical/fisiología , Humanos , Hipotálamo/fisiopatología , Locus Coeruleus/fisiopatología , Trastornos Migrañosos/fisiopatología , Red Nerviosa/fisiopatología , Neuronas/fisiología , Nociceptores/fisiología , Consumo de Oxígeno/fisiología , Sustancia Gris Periacueductal/fisiopatología , Núcleos del Rafe/fisiopatología , Flujo Sanguíneo Regional/fisiología , Cefalea de Tipo Tensional/fisiopatologíaRESUMEN
The evolutionary approach to human anxiety is based on the defensive responses that nonhuman animals show to fear-provoking stimuli. Studies performed mostly on rodents have related areas such as the medial prefrontal cortex, amygdaloid and hypothalamic nuclei, hipoccampal formation, and midbrain central gray to these responses. It is clear, however, that animals show different and sometimes opposite responses according to the threatening stimulus. These responses include immediate reactions such as freezing or flight, behavioral inhibition or avoidance, which are organized by at least partially distinct brain systems. As discussed in this chapter, several pieces of evidence indicate that these brain systems are similar in rodents and primates. In addition, recent neuroimaging studies also suggest dysfunctions in these systems are probably related to anxiety disorders in humans.