RESUMO
Pain perception can be modulated by several factors. Phenomena like temporal summation leads to increased perceived pain, whereas behavioral conditioning can result in analgesic responses. Furthermore, during repeated, identical noxious stimuli, pain intensity can vary greatly in some individuals. Understanding these variations is important, given the increase in investigations that assume stable baseline pain for accurate response profiles, such as studies of analgesic mechanisms. We utilized functional magnetic resonance imaging to examine the differences in neural circuitry between individuals displaying consistent pain ratings and those who experienced variable pain during a series of identical noxious stimuli. We investigated 63 healthy participants: 31 were assigned to a "consistent" group, and 32 were assigned to a "variable" group dependent on pain rating variability. Variable pain ratings were associated with reduced signal intensity in the dorsolateral prefrontal cortex (dlPFC). Furthermore, the dlPFC connectivity with the primary somatosensory cortex and temperoparietal junction was significantly reduced in variable participants. Our results suggest that investigators should consider variability of baseline pain when investigating pain modulatory paradigms. Additionally, individuals with consistent and variable pain ratings differ in their dlPFC activity and connectivity with pain-sensitive regions during noxious stimulation, possibly reflecting the differences in attentional processing and catastrophizing during pain.
Assuntos
Percepção da Dor , Dor , Humanos , Percepção da Dor/fisiologia , Dor/diagnóstico por imagem , Medição da Dor , Atenção , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Córtex Pré-Frontal/fisiologiaRESUMO
OBJECTIVE: To examine injury patterns in adolescent rugby players and determine factors associated with injury risk. DESIGN: Prospective injury surveillance study. SETTING: N=28 Grammar Schools in Ulster, Ireland (2014-2015 playing season). PARTICIPANTS: 825 adolescent rugby players, across in 28 school first XV rugby squads; mean age 16.9â years. MAIN OUTCOME MEASURES: Injuries were classified by body part and diagnosis, and injury incidence using injuries per 1000 match hours of exposure. HRs for injury were calculated through Cox proportional hazard regression after correction for influential covariates. RESULTS: A total of n=426 injuries were reported across the playing season. Over 50% of injuries occurred in the tackle situation or during collisions (270/426), with few reported during set plays. The 3 most common injury sites were head/face (n=102, 23.9%), clavicle/shoulder (n=65, 15.3%) and the knee (n=56, 13.1%). Sprain (n=133, 31.2%), concussion (n=81, 19%) and muscle injury (n=65, 15.3%) were the most common diagnoses. Injury incidence is calculated at 29.06 injuries per 1000 match hours. There were no catastrophic injuries. A large percentage of injuries (208/424) resulted in absence from play for more than 28â days. Concussion carried the most significant time out from play (n=33; 15.9%), followed by dislocations of the shoulder (n=22; 10.6%), knee sprains (n=19, 9.1%), ankle sprains (n=14, 6.7%), hand/finger/thumb (n=11; 5.3%). 36.8% of participants in the study (304/825) suffered at least one injury during the playing season. Multivariate models found higher risk of injury (adjusted HR (AHR); 95% CI) with: higher age (AHR 1.45; 1.14 to 1.83), heavier weight (AHR 1.32; 1.04 to 1.69), playing representative rugby (AHR 1.42; 1.06 to 1.90) and undertaking regular strength training (AHR 1.65; 1.11 to 2.46). Playing for a lower ranked team (AHR 0.67; 0.49 to 0.90) and wearing a mouthguard (AHR 0.70; 0.54 to 0.92) were associated with lower risk of injury. CONCLUSIONS: There was a high incidence of severe injuries, with concussion, ankle and knee ligament injuries and upper limb fractures/dislocations causing greatest time loss. Players were compliant with current graduated return-to-play regulations following concussion. Physical stature and levels of competition were important risk factors and there was limited evidence for protective equipment.
Assuntos
Traumatismos em Atletas/epidemiologia , Futebol Americano/lesões , Adolescente , Concussão Encefálica/epidemiologia , Fraturas Ósseas/epidemiologia , Humanos , Incidência , Irlanda , Masculino , Análise Multivariada , Músculo Esquelético/lesões , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Instituições Acadêmicas , Entorses e Distensões/epidemiologiaRESUMO
Conditioned pain modulation is a powerful analgesic mechanism, occurring when a painful stimulus is inhibited by a second painful stimulus delivered at a different body location. Reduced conditioned pain modulation capacity is associated with the development of some chronic pain conditions and the effectiveness of some analgesic medications. Human lesion studies show that the circuitry responsible for conditioned pain modulation lies within the caudal brainstem, although the precise nuclei in humans remain unknown. We employed brain imaging to determine brainstem sites responsible for conditioned pain modulation in 54 healthy individuals. In all subjects, 8 noxious heat stimuli (test stimuli) were applied to the right side of the mouth and brain activity measured using functional magnetic resonance imaging. This paradigm was then repeated. However, following the fourth noxious stimulus, a separate noxious stimulus, consisting of an intramuscular injection of hypertonic saline into the leg, was delivered (conditioning stimulus). During this test and conditioning stimulus period, 23 subjects displayed conditioned pain modulation analgesia whereas 31 subjects did not. An individual's analgesic ability was not influenced by gender, pain intensity levels of the test or conditioning stimuli or by psychological variables such as pain catastrophizing or fear of pain. Brain images were processed using SPM8 and the brainstem isolated using the SUIT toolbox. Significant increases in signal intensity were determined during each test stimulus and compared between subjects that did and did not display CPM analgesia (p<0.05, small volume correction). The expression of analgesia was associated with reduction in signal intensity increases during each test stimulus in the presence of the conditioning stimulus in three brainstem regions: the caudalis subdivision of the spinal trigeminal nucleus, i.e., the primary synapse, the region of the subnucleus reticularis dorsalis and in the dorsolateral pons in the region of the parabrachial nucleus. Furthermore, the magnitudes of these signal reductions in all three brainstem regions were significantly correlated to analgesia magnitude. Defining conditioned pain modulation circuitry provides a framework for the future investigations into the neural mechanisms responsible for the maintenance of persistent pain conditions thought to involve altered analgesic circuitry.
Assuntos
Tronco Encefálico/fisiopatologia , Percepção da Dor/fisiologia , Dor/fisiopatologia , Adulto , Mapeamento Encefálico , Feminino , Temperatura Alta , Humanos , Imageamento por Ressonância Magnética , Masculino , Dor/psicologia , Medição da Dor , Adulto JovemRESUMO
The temperament dimension of harm avoidance defines an individual's biological tendency to exhibit altering levels of anxious, inhibiting, and cautious behavior. High harm avoidance and anxiety are highly comorbid, likely due to activity in similar neural circuitries involving the dorsal raphe nucleus. Despite the many investigations that have explored personality factors and brain function, none have determined the influence of ongoing activity within dorsal raphe networks on harm avoidance. The aim of this study was to explore such a relationship. In 62 healthy subjects, a series of 180 functional magnetic resonance images covering the entire brain were collected, and each subject completed the 240-item TCI-R questionnaire. Independent component analyses were performed to define the dorsal raphe network and then to determine the regions significantly correlated with harm avoidance. The independent component analyses revealed three signal intensity fluctuation maps encompassing the dorsal raphe nucleus, showing interactions with regions of the amygdala, hippocampus, nucleus accumbens, and prefrontal, insular, and cingulate cortices. Within these systems, the resting signal intensity was significantly coupled to harm avoidance in the bilateral basal amygdala, bilateral ventral hippocampus, bilateral insula, bilateral nucleus accumbens, and medial prefrontal cortex. Note that we could not measure serotonergic output, but instead measured signal changes in the dorsal raphe that likely reflect synaptic activity. These data provide evidence that at rest, signal intensity fluctuations within the dorsal raphe networks are related to harm avoidance. Given the strong relationship between harm avoidance and anxiety-like behaviors, it is possible that ongoing activity within this identified neural circuitry can contribute to an individual developing anxiety disorders.
Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Núcleo Dorsal da Rafe/efeitos dos fármacos , Descanso/fisiologia , Serotonina/farmacologia , Temperamento/efeitos dos fármacos , Adulto , Idoso , Tonsila do Cerebelo/fisiopatologia , Ansiedade/tratamento farmacológico , Ansiedade/fisiopatologia , Transtornos de Ansiedade/tratamento farmacológico , Aprendizagem da Esquiva/fisiologia , Núcleo Dorsal da Rafe/fisiopatologia , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/fisiopatologia , Temperamento/fisiologia , Adulto JovemRESUMO
Accumulated evidence from experimental animal models suggests that neuroplastic changes at the dorsal horn are critical for the maintenance of various chronic musculoskeletal pain conditions. However, to date, no study has specifically investigated whether neuroplastic changes also occur at this level in humans. Using brain imaging techniques, we sought to determine whether anatomical changes were present in the medullary dorsal horn (spinal trigeminal nucleus caudalis) in subjects with the chronic musculoskeletal pain. In twenty-two subjects with painful temporomandibular disorders (TMDs) and forty pain-free controls voxel based morphometry of T1-weighted anatomical images and diffusion tensor images were used to assess regional grey matter volume and microstructural changes within the brainstem and, in addition, the integrity of ascending pain pathways. Voxel based morphometry revealed significant regional grey matter volume decreases in the medullary dorsal horn, in conjunction with alterations in diffusivity properties, namely an increase in mean diffusivity, in TMD subjects. Volumetric and mean diffusivity changes also occurred in TMD subjects in regions of the descending pain modulation system, including the midbrain periaqueductal grey matter and nucleus raphe magnus. Finally, tractography revealed altered diffusivity properties, namely decreased fractional anisotropy, in the root entry zone of the trigeminal nerve, the spinal trigeminal tract and the ventral trigeminothalamic tracts of TMD subjects. These data reveal that chronic musculoskeletal pain in humans is associated with discrete alterations in the anatomy of the medullary dorsal horn, as well as its afferent and efferent projections. These neural changes may be critical for the maintenance of pathological pain.
Assuntos
Tronco Encefálico/patologia , Substância Cinzenta/patologia , Imageamento por Ressonância Magnética/métodos , Síndrome da Disfunção da Articulação Temporomandibular/patologia , Núcleo Inferior Caudal do Nervo Trigêmeo/patologia , Adulto , Idoso , Dor Crônica/patologia , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Corno Dorsal da Medula Espinal/patologiaRESUMO
Persistent neuropathic pain commonly occurs following spinal cord injury (SCI). It remains one of the most challenging management problems in this condition. In order to develop more effective treatments, a better understanding of the neural changes associated with neuropathic SCI pain is required. The aim of this investigation was to use diffusion tensor imaging (DTI) to determine if persistent neuropathic pain following SCI is associated with changes in regional brain anatomy and connectivity. In 23 subjects with complete thoracic SCI, 12 with below-level neuropathic pain and 11 without pain, and 45 healthy control subjects, a series of whole-brain DTI scans were performed. The mean diffusivity (MD) of each voxel was calculated and values compared between groups. This analysis revealed that neuropathic pain following SCI is associated with significant differences in regional brain anatomy. These anatomical changes were located in pain-related regions as well as regions of the classic reward circuitry, that is, the nucleus accumbens and orbitofrontal, dorsolateral prefrontal, and posterior parietal cortices. The right posterior parietal cortex projected to most regions that displayed an anatomical change. Analysis of the fiber tracts connecting areas of MD differences revealed no significance differences in MD values between the SCI pain, SCI no pain, and control groups.
Assuntos
Encéfalo/anatomia & histologia , Encéfalo/fisiopatologia , Rede Nervosa/anatomia & histologia , Rede Nervosa/fisiopatologia , Dor Intratável/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Adulto , Idoso , Imagem de Tensor de Difusão , Feminino , Lateralidade Funcional/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Vias Neurais/anatomia & histologia , Vias Neurais/fisiopatologia , Neuralgia/etiologia , Neuralgia/fisiopatologia , Plasticidade Neuronal/fisiologia , Dor Intratável/etiologia , Traumatismos da Medula Espinal/complicações , Adulto JovemRESUMO
Maintaining high frequency firing of narrow action potentials puts a large metabolic load on fast spiking (FS), perisomatic-inhibitory interneurons compared to their slow-spiking, dendrite targeting counterparts. Although the relationship of action potential (AP) firing and metabolism is firmly established, there is no single method to differentiate interneurons in situ based on their firing properties. In this study, we explore a novel strategy to easily identify the metabolically active FS cells among different classes of interneurons. We found that the oxidation of the fluorescent free radical marker 2,7-dichlorodihydrofluorescein (H2DCF) preferentially occurs in interneurons both in slice cultures and acute brain slices. Despite their morphological heterogeneity, almost all DCF-positive (DCF+) neurons belonged to the cluster of non-accommodating FS interneurons. Furthermore, all FS interneurons expressing parvalbumin (PV) both in slice cultures and in acute slices from tdTomato-PVCre transgenic mice were also DCF+. However, only half of the recorded DCF + cells were also PV+, indicating that H2DCF-oxidation occurs in different interneuron classes characterized by non-accomodating AP-firing. Comprehensively enhancing spontaneous neuronal activity led to mitochondrial oxidation of DCF in pyramidal cells as well as interneurons, suggesting that the apparent selectivity towards interneurons represents differences in the underlying metabolic load. While radical-scavenging, inhibition of APs or NO-synthesis, and iron chelation had no effect on the staining pattern, exposure to the complex-I inhibitor, rotenone, prevented interneuronal DCF accumulation. We conclude that H2DCF oxidation is independent of free radicals but correlates with the intensive oxidative energy metabolism and high mitochondrial mass in interneurons sharing the non-accommodating FS phenotype.
Assuntos
Interneurônios , Parvalbuminas , Potenciais de Ação , Animais , Camundongos , Camundongos Transgênicos , Células PiramidaisRESUMO
C.B-20 ( Ighb ) mice challenged with BALB/c ( Igha ) spleen cells (or vice-versa) generate cytotoxic T lymphocytes (CTL) that recognize an antigen, H-40, controlled by an Igh-linked gene. The gene maps to the Igh-C region end of the Igh complex, telomeric to Tsu in the region of Pre-1. At least three alleles, a, b, and c, can be defined. Using a cold target competition assay, no polymorphism of the a allele was detected. Both surface Igh-5a positive and negative spleen cells from (C.B-20 X BALB/c)F1 animals express the a allele of the antigen, indicating that this gene is not allelically excluded. Recognition of the target antigen by CTL is restricted by the D-end of H-2d. The tissue distribution of H-40 was explored using both bulk-cultured and cloned CTL. The antigen is expressed on surface immunoglobulin positive (sIg+) cells and correlates with the expression of sIgM. This was determined by analysis of several B lymphomas as well as of other tumors that varied in their extent of expression of sIg. Four subclones of BCL1 were analyzed. Two of the subclones are sIg+ and express H-40, while two other subclones are sIg- and H-40-. Thus, these data define an Igh-linked gene, separate from immunoglobulin structural loci, that controls an antigen expressed on sIg+ cells. Possible mechanisms to account for this finding are discussed.
Assuntos
Linfócitos B , Antígenos de Histocompatibilidade/genética , Cadeias Pesadas de Imunoglobulinas/genética , Região Variável de Imunoglobulina/genética , Linfoma/imunologia , Linfócitos T Citotóxicos/imunologia , Alelos , Animais , Regulação da Expressão Gênica , Antígenos H-2/genética , Hibridização Genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos , Polimorfismo Genético , Baço/citologiaRESUMO
A debilitating consequence of complete spinal cord injury (SCI) is the loss of motor control. Although the goal of most SCI treatments is to re-establish neural connections, a potential complication in restoring motor function is that SCI may result in anatomical and functional changes in brain areas controlling motor output. Some animal investigations show cell death in the primary motor cortex following SCI, but similar anatomical changes in humans are not yet established. The aim of this investigation was to use voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) to determine if SCI in humans results in anatomical changes within motor cortices and descending motor pathways. Using VBM, we found significantly lower gray matter volume in complete SCI subjects compared with controls in the primary motor cortex, the medial prefrontal, and adjacent anterior cingulate cortices. DTI analysis revealed structural abnormalities in the same areas with reduced gray matter volume and in the superior cerebellar cortex. In addition, tractography revealed structural abnormalities in the corticospinal and corticopontine tracts of the SCI subjects. In conclusion, human subjects with complete SCI show structural changes in cortical motor regions and descending motor tracts, and these brain anatomical changes may limit motor recovery following SCI.
Assuntos
Imagem de Difusão por Ressonância Magnética , Vias Eferentes/patologia , Córtex Motor/patologia , Plasticidade Neuronal , Traumatismos da Medula Espinal/patologia , Medula Espinal/patologia , Vértebras Torácicas/lesões , Adulto , Humanos , Pessoa de Meia-Idade , Vértebras Torácicas/patologia , Adulto JovemRESUMO
Human studies conducted more than half a century ago have suggested that superficial pain induces excitatory effects on the sympathetic nervous system, resulting in increases in blood pressure (BP) and heart rate (HR), whereas deep pain is believed to cause vasodepression. To date, no studies have addressed whether deep or superficial pain produces such differential effects on muscle sympathetic nerve activity (MSNA). Using microneurography we recorded spontaneous MSNA from the common peroneal nerve in 13 awake subjects. Continuous blood pressure was recorded by radial arterial tonometry. Deep pain was induced by intramuscular injection of 0.5 ml hypertonic saline (5%) into the tibialis anterior muscle, superficial pain by subcutaneous injection of 0.2 ml hypertonic saline into the overlying skin. Muscle pain, with a mean rating of 4.9 +/- 0.8 (S.E.M.) on a 0-10 visual analog scale (VAS) and lasting on average 358 +/- 32 s, caused significant increases in MSNA (43.9 +/- 10.0%), BP (5.4 +/- 1.1%) and HR (7.0 +/- 2.0%) - not the expected decreases. Skin pain, rated at 4.9 +/- 0.6 and lasting 464 +/- 54 s, also caused significant increases in MSNA (38.2 +/- 12.8%), BP (5.1 +/- 2.1%) and HR (5.6 +/- 2.0%). The high-frequency (HF) to low-frequency (LF) ratio of heart rate variability (HRV) increased from 1.54 +/- 0.25 to 2.90 +/- 0.45 for muscle pain and 2.80 +/- 0.52 for skin pain. Despite the different qualities of deep (dull and diffuse) and superficial (burning and well-localized) pain, we conclude that pain originating in muscle and skin does not exert a differential effect on muscle sympathetic nerve activity, both causing an increase in MSNA and an increase in the LF:HF ratio of HRV. Whether this holds true for longer lasting experimental pain remains to be seen.
Assuntos
Músculo Esquelético/fisiopatologia , Dor/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Adulto , Pressão Sanguínea , Feminino , Frequência Cardíaca , Humanos , Masculino , Músculo Esquelético/inervação , Dor/etiologia , Medição da Dor , Solução Salina Hipertônica/administração & dosagem , Solução Salina Hipertônica/toxicidade , Pele/inervação , Pele/fisiopatologiaRESUMO
There is evidence in experimental animals that deep and superficial pain exert differential effects on cutaneous sympathetic activity. Skin sympathetic nerve activity (SSNA) was recorded from the common peroneal nerve of awake human subjects and injections of 0.5 ml hypertonic saline was made into the tibialis anterior muscle (causing a deep, dull ache) or 0.2 ml into the overlying skin (causing a sharp burning pain) at unexpected times. Both deep and superficial pain caused increases in SSNA immediately on injection and preceding the onset of pain for both muscle and skin pain (10.1 +/- 2.4 vs. 15.3 +/- 5.3 s; muscle versus skin, respectively). SSNA increases were short lasting (104.2 +/- 13.4 vs. 81.8 +/- 11.7 s; muscle versus skin pain) and did not follow muscle and skin pain profiles. Sweat release occurred following both intramuscular and subcutaneous injections of hypertonic saline. While muscle or skin pain invariably caused changes in skin blood flow as well as increases in sweat release, skin blood flow increased in females and decreased in males. We conclude that both acute muscle and skin pain cause an increase in SSNA, sweat release and gender-dependent changes in skin blood flow.
Assuntos
Dor/fisiopatologia , Nervo Fibular/fisiologia , Pele/inervação , Sistema Nervoso Simpático/fisiopatologia , Adolescente , Feminino , Humanos , Masculino , Músculo Esquelético/fisiopatologia , Dor/induzido quimicamente , Medição da Dor , Fluxo Sanguíneo Regional , Solução Salina Hipertônica , Índice de Gravidade de Doença , Caracteres Sexuais , Pele/irrigação sanguínea , Suor/fisiologia , Adulto JovemRESUMO
The neural mechanisms underlying the development and maintenance of chronic pain following nerve injury remain unclear. There is growing evidence that chronic neuropathic pain is associated with altered thalamic firing patterns, thalamocortical dysrhythmia and altered infra-slow oscillations in ascending pain pathways. Preclinical and post-mortem human studies have revealed that neuropathic pain is associated with prolonged astrocyte activation in the dorsal horn and we have suggested that this may result in altered gliotransmission, which results in altered resting neural rhythm in the ascending pain pathway. Evidence of astrocyte activation above the level of the dorsal horn in living humans is lacking and direct measurement of astrocyte activation in living humans is not possible, however, there is evidence that regional alterations in T2 relaxation times are indicative of astrogliosis. The aim of this study was to use T2 relaxometry to explore regional brain anatomy of the ascending pain pathway in individuals with chronic orofacial neuropathic pain. We found that in individuals with trigeminal neuropathic pain, decreases in T2 relaxation times occurred in the region of the spinal trigeminal nucleus and primary somatosensory cortex, as well as in higher order processing regions such as the dorsolateral prefrontal, cingulate and hippocampal/parahippocampal cortices. We speculate that these regional changes in T2 relaxation times reflect prolonged astrocyte activation, which results in altered brain rhythm and ultimately the constant perception of pain. Blocking prolonged astrocyte activation may be effective in preventing and even reversing the development of chronic pain following neural injury.
Assuntos
Encéfalo/fisiopatologia , Dor Crônica/fisiopatologia , Neuralgia/fisiopatologia , Relaxamento/fisiologia , Adulto , Encéfalo/metabolismo , Dor Crônica/metabolismo , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Medição da Dor/métodosRESUMO
It has been proposed that pain competes with other attention-demanding stimuli for cognitive resources, and many chronic pain patients display significant attention and mental flexibility deficits. These alterations may result from disruptions in the functioning of the default mode network (DMN) which plays a critical role in attention, memory, prospection and self-processing, and recent investigations have found alterations in DMN function in multiple chronic pain conditions. Whilst it has been proposed that these DMN alterations are a characteristic of pain that is chronic in nature, we recently reported altered oscillatory activity in the DMN during an acute, 5 minute noxious stimulus in healthy control subjects. We therefore hypothesize that altered DMN activity patterns will not be restricted to those in chronic pain but instead will also occur in healthy individuals during tonic noxious stimuli. We used functional magnetic resonance imaging to measure resting state infra-slow oscillatory activity and functional connectivity in patients with chronic orofacial pain at rest and in healthy controls during a 20-minute tonic pain stimulus. We found decreases in oscillatory activity in key regions of the DMN in patients with chronic pain, as well as in healthy controls during tonic pain in addition to changes in functional connectivity between the posterior cingulate cortex and areas of the DMN in both groups. The results show that similar alterations in DMN function occur in healthy individuals during acute noxious stimuli as well as in individuals with chronic pain. These DMN changes may reflect the presence of pain per se and may underlie alterations in attentional processes that occur in the presence of pain.
Assuntos
Dor Aguda/fisiopatologia , Encéfalo/fisiopatologia , Dor Crônica/fisiopatologia , Dor Aguda/diagnóstico por imagem , Adulto , Atenção/fisiologia , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Dor Crônica/diagnóstico por imagem , Dor Facial/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologiaRESUMO
OBJECTIVES: To establish patterns of subsequent injury in U18 rugby, to quantify the burden of within season injury recurrence. DESIGN: Secondary analysis of prospective data. SETTING: 28 Schools in Ireland. PARTICIPANTS: 825 male rugby players (aged 15-18 years). MAIN OUTCOME MEASURES: Subsequent injuries were classified as: new, local or recurrent (same site and type as index injury). All recurrent injuries were sub-grouped by body part and diagnosis. Burden was based on frequency, days lost and injury proportion ratios. RESULTS: A total of 426 injuries were eligible for analysis, of which, 121 were subsequent injuries. The majority of subsequent injuries involved a different body part than their index injury. There were nâ¯=â¯23 cases of within season recurrence. 78% of recurrences occurred within 2 months of return to play. Recurrent injuries comprised 5% of all injuries and their cumulative time loss was 1073 days. Recurrent injury to the ankle ligaments, lumbar muscles and concussions carried the greatest burden. CONCLUSION: The burden of recurrent injury in U18 rugby is lower than in the professional game. However, this population could benefit from targeted secondary prevention efforts including reconsideration of return-to-play protocols for ankle sprain, lumbar muscles and potentially concussion.
Assuntos
Traumatismos em Atletas/epidemiologia , Futebol Americano/lesões , Adolescente , Humanos , Incidência , Irlanda , Masculino , Recidiva , Volta ao EsporteRESUMO
All pain is unpleasant, but different perceptual and emotional qualities are characteristic of pain originating in different structures. Pain of superficial (cutaneous) origin usually is sharp and restricted, whereas pain of deep origin (muscle/viscera) generally is dull and diffuse. Despite the differences it has been suggested previously that all pain is mediated by an invariant set ("neuromatrix") of brain structures. However, we report here, using functional magnetic resonance imaging (fMRI), that striking regional differences in brain activation patterns were the rule. Signal differences were found in regions implicated in emotion (perigenual cingulate cortex), stimulus localization and intensity (somatosensory cortex) and motor control (motor cortex, cingulate motor area). Further, most fMRI signal changes matched perceived changes in pain intensity. These findings clearly indicate that distinct neural activity patterns in distinct sets of brain structures are evoked by pain originating from different tissues of the body. Further, we suggest that these differences underlie the different perceptual and emotional reactions evoked by deep versus superficial pain.
Assuntos
Potenciais Somatossensoriais Evocados , Limiar da Dor , Dor/classificação , Dor/fisiopatologia , Prosencéfalo/fisiopatologia , Adulto , Mapeamento Encefálico , Feminino , Humanos , Imageamento por Ressonância Magnética , MasculinoRESUMO
A maximal inspiratory breath hold (inspiratory capacity apnea) against a closed glottis evokes a large and sustained increase in muscle sympathetic nerve activity (MSNA). Because of its dependence on a high intrathoracic pressure, it has been suggested that this maneuver causes unloading of the low-pressure baroreceptors, known to increase MSNA. To determine the central origins of this sympathoexcitation, we used functional magnetic resonance imaging to define the loci and time course of activation of different brain areas. We hypothesized that, as previously shown for the Valsalvsa maneuver, discrete but widespread regions of the brain would be involved. In 15 healthy human subjects, a series of 90 gradient echo echo-planar image sets was collected during three consecutive 40-s inspiratory capacity apneas using a 3-T scanner. Global signal intensity changes were calculated and subsequently removed by using a detrending technique, which eliminates the global signal component from each voxel's signal intensity change. Whole brain correlations between changes in signal intensity and the known pattern of MSNA during the maneuver were performed on a voxel-by-voxel basis, and significant changes were determined by using a random-effects analysis procedure (P < 0.01, uncorrected). Significant signal increases emerged in multiple areas, including the rostral lateral medulla, cerebellar nuclei, anterior insula, dorsomedial hypothalamus, anterior cingulate, and lateral prefrontal cortexes. Decreases in signal intensity occurred in the dorsomedial and caudal lateral medulla, cerebellar cortex, hippocampus, and posterior cingulate cortex. Given that many of these sites have roles in cardiovascular control, the sustained increase in MSNA during an inspiratory capacity apnea is likely to originate from a distributed set of discrete areas.
Assuntos
Apneia/fisiopatologia , Encéfalo/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Músculo Esquelético/inervação , Músculo Esquelético/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Manobra de Valsalva , Adulto , Mapeamento Encefálico/métodos , Feminino , Humanos , Capacidade Inspiratória , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Pain catastrophizing significantly affects an individual's experience of pain. High pain catastrophizing is associated with increased fear avoidance behaviours, pain intensity and disability. The aim of this investigation was to determine the effect of pain catastrophizing on ongoing brain activity and movement-evoked brain activity during acute orofacial muscle pain. METHODS: Thirty-four healthy, pain-free subjects were recruited. In 17 subjects, the effect of catastrophizing on regional brain activity was determined. In 19 subjects, functional magnetic resonance imaging was used to determine the effects of pain catastrophizing on brain activation patterns during jaw movements in the presence of ongoing pain. RESULTS: We found that in the presence of pain, catastrophizing was significantly correlated with activity in multi-sensory integrative brain regions, including the dorsolateral and medial prefrontal cortices. Importantly, this relationship did not exist when subjects were not experiencing pain. In addition, during repetitive open-close jaw movements in the presence of pain, activity in the primary motor cortex, cerebellar cortex and the trigeminal motor nucleus was positively correlated with pain catastrophizing scores. In contrast, in the dorsolateral prefrontal cortex, as pain catastrophizing scores increased, the magnitude of signal intensity change during jaw movements decreased. Again, no such relationships occurred when the individual was not in pain. CONCLUSIONS: These data show that during pain, catastrophic thinking has a significant impact on activity in motor and sensory integrative regions. Reducing negative coping strategies may be an effective means in reducing fear avoidance behaviours and the intensity of ongoing pain.
Assuntos
Encéfalo/fisiopatologia , Catastrofização/fisiopatologia , Catastrofização/psicologia , Dor Facial/psicologia , Atividade Motora/fisiologia , Mialgia/psicologia , Adulto , Estudos de Casos e Controles , Dor Facial/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Mialgia/fisiopatologia , Medição da Dor/métodos , Adulto JovemRESUMO
CBA/J mice were immunosuppressed by repeated administration of goat antibody specific for mu chain of immunoglobulin M (IgM) and tested for nonspecific and Candida albicans-specific immune responses. Immunosuppression was demonstrated by a dramatic reduction in the number of antibody-forming cells in the spleens of anti-mu-treated mice when immunized with sheep erythrocytes, by greatly reduced in vitro responsiveness of both spleen and lymph node lymphocytes from anti-mu-treated mice to lipopolysaccharide, and by a large reduction in the number of splenic IgM-positive cells. T cell function, on the other hand, appeared to be relatively unaltered in anti-mu-treated animals, in the cytotoxic T lymphocyte activity against an allogeneic target was similar in splenocyte cultures from anti-mu- and mock-treated animals, and splenic and lymph node lymphocytes proliferated in response to concanavalin A in a lymphocyte stimulation assay. Moreover, Candida-specific delayed hypersensitivity to two different Candida antigens, one cell wall-derived (GP) and the other cell membrane-derived (BEX), was of comparable intensity in immunosuppressed and normal animals. When anti-mu- and mock-treated mice were immunized by the cutaneous inoculation of viable C. albicans blastospores and then challenged intravenously to assess the development of protective immunity, only mock-treated animals, male and female, had significant (p less than or equal to 0.05) protective responses demonstrable by reduction in the number of colony-forming units cultured from their kidneys 28 days after intravenous challenge. If consideration was given to the number of animals which had cleared Candida completely from the kidney, however, there appeared to be protective responses operative in the female anti-mu-treated animals as well. Neither anti-mu-treated males nor females, when immunized and challenged with C. albicans, produced Candida-specific antibody detectable by counterimmunoelectrophoresis, whereas all immunized and challenged mock-treated animals produced antibody. The data are consistent with the hypothesis that anti-mu treatment has little effect on multiple cellular immune functions, including those specific for C. albicans, and the combination of antibody, cell-mediated immunity and innate defenses are responsible for solid systemic defense against the fungus.
Assuntos
Anticorpos Anti-Idiotípicos/imunologia , Candida/imunologia , Tolerância Imunológica , Imunidade Inata , Imunoglobulina M/imunologia , Cadeias mu de Imunoglobulina/imunologia , Animais , Linfócitos B/imunologia , Feminino , Hipersensibilidade Tardia , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos CBA , Linfócitos T/imunologiaRESUMO
The transmembrane glycoprotein (gp41 or TM) of HIV-1 contains limited sequence similarity to TM of some immunosuppressive animal retroviruses. A specific HIV-1 TM sequence, denoted CS3, inhibits T-cell activation in vitro and antibody specific to CS3 has been linked to the absence of disease. CS3, when conjugated to human serum albumin (HSA) and labeled with fluorescein, binds specifically to CD4+ cell lines. Cross-linking of CS3-HSA to its binding activity on the CD4+ cell line RH9 reveals a putative subunit size of approximately 44 kD. Incubation of RH9 cells with CS3-HSA prior to addition of HIV-1 prevented HIV-1-mediated cell lysis and inhibited infection. These results suggest that the CS3 region of TM plays an important role in the pathogenesis of the AIDS virus, HIV-1.
Assuntos
Proteína gp41 do Envelope de HIV/metabolismo , HIV-1/imunologia , Receptores Virais/análise , Síndrome da Imunodeficiência Adquirida/etiologia , Síndrome da Imunodeficiência Adquirida/imunologia , Sequência de Aminoácidos , Linfócitos T CD4-Positivos/microbiologia , Reagentes de Ligações Cruzadas , Efeito Citopatogênico Viral , Humanos , Ativação Linfocitária , Dados de Sequência Molecular , Proteínas Recombinantes/imunologia , Sensibilidade e Especificidade , Células Tumorais CultivadasRESUMO
Within the caudal medulla there are two regions whose activation leads to vasodepression and bradycardia, the caudal ventrolateral medulla and a discrete region of the caudal midline medulla. This study investigated, in the halothane anaesthetized rat, the contribution of these two vasodepressor regions to "homeostatic" and "behaviourally-coupled" cardiovascular regulation. In an initial set of experiments the contribution of each of these two regions to the hypotension and bradycardia evoked by acute hypovolaemia (15% haemorrhage) was investigated. It was found that inactivation of the caudal midline medulla significantly attenuated (cobalt chloride) or completely blunted (lignocaine) the hypotension and bradycardia evoked by acute hypovolaemia. In contrast, inactivation of the caudal ventrolateral medulla using cobalt chloride, although attenuating the magnitude of the hypotension and completely blocking the bradycardia, did not delay the onset of the hypotension evoked by acute hypovolaemia. The caudal ventrolateral medulla is known to be critical in homeostatic cardiovascular control through the expression of the "baroreceptor reflex" and the hypotension and bradycardia evoked by activation of cardiopulmonary afferents. In a second series of experiments we found inactivation of the caudal midline medulla played no role in baroreflex-evoked bradycardia (i.v. phenylephrine) or the hypotension and bradycardia evoked by cardiopulmonary afferent activation (i.v. 5-hydroxytryptamine). These data suggest that the caudal midline medulla and caudal ventrolateral medulla play different roles in cardiovascular control. The caudal ventrolateral medulla is involved in mediating cardiovascular changes associated with a variety of stimuli including "homeostatic" and "behaviourally-coupled" cardiovascular changes, whereas the caudal midline medulla is critical for mediating "behaviourally-coupled" changes in arterial pressure and heart rate.