Several lines of evidence affirm a positive role for exercise in the management of migraine. This review highlights the latest research supporting this view, covering not only its epidemiologic aspects but also the pain modulatory systems that are likely to be engaged by exercise. Recent research provides broad and consistent evidence indicating that cardiovascular exercise can activate multiple pain modulatory mechanisms, if not the underlying mechanisms that initiate the attack. Specifically, a synthesis of independent lines of recent research would indicate that exercise activates endogenous neurotransmitter signals that could be effective in reducing the intensity of migraine pain, though it may not have a direct effect on its overall frequency or duration.
Photophobia refers to a sensory disturbance provoked by light. However, because it arises distinctly in a broad range of clinical conditions, its definition remains elusive. Many underscore the painful sensory aspects of photophobia, while others emphasize its unpleasant, affective qualities. To add further complexity, recent discoveries in photophobia research have raised disparate and potentially conflicting results. In this installment of an occasional series, we asked clinicians and scientists to give their interpretation of what these discoveries tell us about photophobia in the clinic, and vice versa.
Pain sometimes has a throbbing, pulsating quality, particularly when it is severe and disabling. We recently challenged the presumption that this throbbing quality is a sensory experience of arterial pulsations, but were unable to offer an alternative explanation for its rhythmic character. Here we report a case study of a woman with a history of daily headache consistent with the diagnosis of chronic migraine, but whose throbbing quality persisted long after the resolution of the headache. This chronic, daily, and persistent throbbing sensation, in the absence of headache pain, prompted closer examination for its neurophysiological correlate. By simultaneously recording the subjective report of the throbbing rhythm, arterial pulse, and high-density electroencephalogram, we found that the subjective throbbing rate (48±1.7beats per minute) and heart rate (68±2beats per minute) were distinct, in accord with our previous observations that the 2 are unrelated. On spectral analysis of the electroencephalogram, we found that the overall amount of activity in the alpha range (8 to 12Hz), or alpha power, increased in association with greater throbbing intensity. In addition, we also found that the rhythmic oscillations of overall alpha power, the so-called modulations of alpha power, coincided with the timing of the throbbing rhythm, and that this synchrony, or coherence, was proportional to the subjective intensity of the throbbing quality. This index case will motivate further studies whose aim is to determine whether modulations of alpha power could more generally represent a neurophysiological correlate of the throbbing quality of pain.
To provide an in-depth analysis of seven well-reported studies that examined electrodermal activity (EDA) at acupuncture points with regard to three commonly held tenets of acupuncture: (1) EDA at pathology-related acupuncture points is distinguishable from non-pathology-related acupuncture points; (2) EDA at acupuncture points can assist in diagnosing and monitoring therapeutic progress; and (3) EDA at acupuncture points is able to identify substances that are either therapeutically beneficial or toxic to an individual.
As the intermediate layer between the muscle and skin, the subcutaneous tissue frequently experiences shear and lateral stresses whenever the body is in motion. However, quantifying such stresses in vivo is difficult. The lack of such measures is partly responsible for our poor understanding of the biomechanical behaviors of subcutaneous tissue. In this study, we employ both ultrasound imaging and a novel spatial anisotropy measure - incorporating Morans I spatial autocorrelation calculations - to investigate the structuromechanical features of subcutaneous tissues within the extremities of 16 healthy volunteers. This approach is based on the understanding that spatial anisotropy can be an effective surrogate for the summative, tensile forces experienced by biological tissue. We found that spatial anisotropy in the arm, thigh and calf was attributed to the echogenic bands spanning the width of the ultrasound images. In both univariable and multivariable analyses, the calf was significantly associated with greater anisotropy compared with the thigh and arm. Spatial anisotropy was inversely related to subcutaneous thickness, and was significantly increased with longitudinally oriented probe images compared with transversely orientated images. Maximum peaks in spatial anisotropy were frequently observed when the longitudinally oriented ultrasound probe was swept across the extremity, suggesting that longitudinal channels with greater tension exist in the subcutaneous layer. These results suggest that subcutaneous biomechanical tension is mediated by collagenous/echogenic bands, greater in the calf compared with the thigh and arm, increased in thinner individuals, and maximal along longitudinal trajectories parallel to the underlying muscle. Spatial anisotropy analysis of ultrasound images has yielded meaningful patterns and may be an effective means to understand the biomechanical strain patterns within the subcutaneous tissue of the extremities.
Although fascial bands within the subcutaneous (SQ) layer are commonly seen in ultrasound images, little is known about their functional role, much less their structural characteristics. This studys objective is to describe the morphological features of SQ fascial bands and to systematically evaluate the bands using image analyses tools and morphometric measures.
Electrodermal activity (EDA) at acupuncture points (acupoints) has been investigated for its utility as a diagnostic aid, a therapeutic monitoring tool, and a physiological outcome measure. The research methodologies reported in published trials, however, vary considerably and publications often lack sufficient details about electrical instrumentation, technical procedures, laboratory conditions, recorded measures, and control comparisons to permit a critical appraisal of the studies or to replicate promising findings. We developed a 10-category (54 subitems) Quality of Reporting scale based on technical issues associated with EDA measurements, publication requirements for reporting EDA in the psychophysiological literature, and recommendations from the CONSORT Statement for reporting clinical trials. Using our Quality of Reporting scale, we extracted data from 29 studies that evaluated EDA at acupoints in patients and generated weighted scores for each of the 10 categories of essential information. Only 9 of the 29 studies reviewed scored a mean of greater than 50% for reporting details of essential information. To rigorously build a program of research on EDA at acupoints we need to standardize research methodology and reporting protocols. We propose a checklist of recommended informational items to report in future clinical trials that record EDA at acupoints.
The characteristic throbbing quality of migraine pain is often attributed to the periodic activation of trigeminovascular sensory afferents triggered by the distension of cranial arteries during systole, but direct evidence for this model has been elusive.
In October 2007, a National Center for Complementary and Alternative Medicine (NCCAM)-sponsored workshop, entitled "Applying Principles from Complex Systems to Studying the Efficacy of CAM Therapies," was held at Georgetown University in Washington, DC. Over a 2-day period, the workshop engaged a small group of experts from the fields of complementary and alternative medicine (CAM) research and complexity science to discuss and examine ways in which complexity science can be applied to CAM research. After didactic presentations and small-group discussions, a number of salient themes and ideas emerged. This paper article describes the workshop program and summarizes these emergent ideas, which are divided into five broad categories: (1) introduction to complexity; (2) challenges to CAM research; (3) applications of complexity science to CAM; (4) CAM as a model of complexity applied to medicine; and (5) future directions. This discusses possible benefits and challenges associated with applying complexity science to CAM research. By providing an introductory framework for this collaboration and exchange, it is hoped that this article may stimulate further inquiry into this largely unexplored area of research.
There is little precedent for a medication-induced spontaneous intracranial hypotension/cerebrospinal fluid (CSF) hypovolemia (SIH). This case history of a woman with low CSF pressure, orthostatic headache, and radiographic findings consistent with SIH but without a detectable leak was notable for its association, both onset and resolution, with the use of the calcineurin inhibitor tacrolimus (FK506). A literature review for potential causes of a tacrolimus-induced CSF hypotension suggests many potential mechanisms of action, including effects on blood brain barrier and dural compliance, and supports further vigilance for this condition in the medically complex setting of tacrolimus use.
The scientific basis for acupuncture meridians is unknown. Past studies have suggested that acupuncture meridians are physiologically characterized by low electrical impedance and anatomically associated with connective tissue planes. We are interested in seeing whether acupuncture meridians are associated with lower electrical impedance and whether ultrasound-derived measures--specifically echogenic collagenous bands--can account for these impedance differences.
Anatomic changes and positional variability during intensity-modulated radiation therapy (IMRT) for head and neck cancer can lead to clinically significant dosimetric changes. We report our single-institution experience using an adaptive protocol and correlate these changes with anatomic and positional changes during treatment.
To determine whether electrodermal measures at Jing-Well acupuncture points, "indicator" points located at the tips of fingers and toes are associated with clinical measures in adolescent women with chronic pelvic pain.
According to "Wolffs Law", bone is deposited and reinforced at areas of greatest stress. From a clinical perspective, this "law" is supported by the strong association between bone density and physical activity. From a mechanistic standpoint, however, the law presents a challenge to scientists seeking to understand how osteocytes and osteoblasts sense the mechanical load. In the 1960s, collagen piezoelectricity was invoked as a potential mechanism by which osteocytes could detect areas of greater stress but piezoelectricity diminished in importance as more compelling mechanisms, such as streaming potential, were identified. In addition, accumulating evidence for the role of fluid-related shear stress in osteocytes mechanosensory function has made piezoelectricity seemingly more obsolete in bone physiology. This review critically evaluates the role of collagen piezoelectricity (if any) in Wolffs Law--specifically, the evidence regarding its involvement in strain-generated potentials, existing alternate mechanisms, the present understanding of bone mechanosensation, and whether piezoelectricity serves an influential role within the context of this newly proposed mechanism. In addition to reviewing the literature, this review generates several hypotheses and proposes future research to fully address the relevance of piezoelectricity in bone physiology.
With 54 degrees of freedom from the skull to mandible to C7, ensuring adequate immobilization for head-and-neck radiotherapy (RT) is complex. We quantify variations in skull, mandible, and cervical spine movement between RT sessions.
Objective. Acupuncture points are reportedly distinguishable by their electrical properties. However, confounders arising from skin-to-electrode contact used in traditional electrodermal methods have contributed to controversies over this claim. The Scanning Kelvin Probe is a state-of-the-art device that measures electrical potential without actually touching the skin and is thus capable of overcoming these confounding effects. In this study, we evaluated the electrical potential profiles of acupoints LI-4 and PC-6 and their adjacent controls. We hypothesize that acupuncture point sites are associated with increased variability in potential compared to adjacent control sites. Methods. Twelve healthy individuals were recruited for this study. Acupuncture points LI-4 and PC-6 and their adjacent controls were assessed. A 2?mm probe tip was placed over the predetermined skin site and adjusted to a tip-to-sample distance of 1.0?mm under tip oscillation settings of 62.4?Hz frequency. A 6 × 6 surface potential scan spanning a 1.0?cm?×?1.0?cm area was obtained. Results. At both the PC-6 and LI-4 sites, no significant differences in mean potential were observed compared to their respective controls (Wilcoxon rank-sum test, P = 0.73 and 0.79, resp.). However, the LI-4 site was associated with significant increase in variability compared to its control as denoted by standard deviation and range (P = 0.002 and 0.0005, resp.). At the PC-6 site, no statistical differences in variability were observed. Conclusion. Acupuncture points may be associated with increased variability in electrical potential.
Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) are the only functional photoreceptive cells in the eye of newborn mice. Through postnatal day 9, in the absence of functional rods and cones, these ipRGCs mediate a robust avoidance behavior to a light source, termed negative phototaxis. To determine whether this behavior is associated with an aversive experience in neonatal mice, we characterized light-induced vocalizations and patterns of neuronal activation in regions of the brain involved in the processing of aversive and painful stimuli. Light evoked distinct melanopsin-dependent ultrasonic vocalizations identical to those emitted under stressful conditions, such as isolation from the litter. In contrast, light did not evoke the broad-spectrum calls elicited by acute mechanical pain. Using markers of neuronal activation, we found that light induced the immediate-early gene product Fos in the posterior thalamus, a brain region associated with the enhancement of responses to mechanical stimulation of the dura by light, and thought to be the basis for migrainous photophobia. Additionally, light induced the phosphorylation of extracellular-related kinase (pERK) in neurons of the central amygdala, an intracellular signal associated with the processing of the aversive aspects of pain. However, light did not activate Fos expression in the spinal trigeminal nucleus caudalis, the primary receptive field for painful stimulation to the head. We conclude that these light-evoked vocalizations and the distinct pattern of brain activation in neonatal mice are consistent with a melanopsin-dependent neural pathway involved in processing light as an aversive but not acutely painful stimulus.
Aging is typically associated with progressive multi-system impairment that leads to decreased physical and cognitive function and reduced adaptability to stress. Due to its capacity to characterize complex dynamics within and between physiological systems, the emerging field of complex systems biology and its array of quantitative tools show great promise for improving our understanding of aging, monitoring senescence, and providing biomarkers for evaluating novel interventions, including promising mind-body exercises, that treat age-related disease and promote healthy aging.
The Kelvin probe measures surface electrical potential without making physical contact with the specimen. It relies on capacitive coupling between an oscillating metal tip that is normal to a specimens surface. Kelvin probes have been increasingly used to study surface and electrical properties of metals and semiconductors and are capable of detecting material surface potentials with submillivolt resolution at a micrometer spatial scale. Its capability for measuring electrical potential without being confounded by electrode-specimen contact makes extending its use towards biological materials particularly appealing. However, the theoretical basis for applying the Kelvin probe to dielectric or partially conductive materials such as biological tissue has not been evaluated and remains unclear. This study develops the theoretical basis underlying Kelvin probe measurements in five theoretical materials: highly conductive, conductive dielectric with rapid charge relaxation, conductive dielectric with slow charge relaxation, perfect dielectric, and tissue with a bulk serial resistance. These theoretically derived equations are then computationally analyzed using parameters from both theoretical specimens and actual biomaterials-including wet skin, dry skin, cerebrospinal fluid, and tendon. Based on these analyses, a Kelvin probe performs in two distinct ways depending on the charge relaxation rates of the sample: The specimen is treated either as a perfect dielectric or as highly conductive material. Because of their rapid relaxation rate and increased permittivity biomaterials behave similarly to highly conductive materials, such as metal, when evaluated by the Kelvin probe. These results indicate that the Kelvin probe can be readily applied to studying the surface potential of biological tissue.
Skull base plasmacytomas are rare and difficult to differentiate clinically and radiologically from other tumors of the head and neck. Because of the risk of progression to multiple myeloma, early diagnosis is essential. We report the case of a 65-year-old woman who presented with left-sided conductive hearing loss and an external auditory canal mass. The tumor was removed along with much of the tympanic membrane, and it was found to be a plasmacytoma. The patient was subsequently diagnosed with multiple myeloma and treated with chemoradiation before being lost to follow-up.
The selective 5-HT? receptor agonist sumatriptan is an effective therapeutic for migraine pain yet the antimigraine mechanisms of action remain controversial. Pain-responsive fibres containing calcitonin gene-related peptide (CGRP) densely innervating the cranial dura mater are widely believed to be an essential anatomical substrate for the development of migraine pain. 5-HT? receptors in the dura colocalize with CGRP fibres in high density and thus provide a possible peripheral site of action for sumatriptan. In the present study, we used high-resolution optical imaging selectively within individual mouse dural CGRP nociceptive fibre terminations and found that application of sumatriptan caused a rapid, reversible dose-dependent inhibition in the amplitude of single action potential evoked Ca²? transients. Pre-application of the 5-HT? antagonist GR 127935 or the selective 5-HT(1D) antagonist BRL 15572 prevented inhibition while the selective 5-HT(1B) antagonist SB 224289 did not, suggesting this effect was mediated selectively through the 5-HT(1D) receptor subtype. Sumatriptan inhibition of the action potential evoked Ca²? signaling was mediated selectively through N-type Ca²? channels. Although the T-type Ca²? channel accounted for a greater proportion of the Ca²? signal it did not mediate any of the sumatriptan inhibition. Our findings support a peripheral site of action for sumatriptan in inhibiting the activity of dural pain fibres selectively through a single Ca²? channel subtype. This finding adds to our understanding of the mechanisms that underlie the clinical effectiveness of 5-HT? receptor agonists such as sumatriptan and may provide insight for the development of novel peripherally targeted therapeutics for mitigating the pain of migraine.
Pain can have a throbbing quality, especially when it is severe and disabling. It is widely held that this throbbing quality is a primary sensation of ones own arterial pulsations, arising directly from the activation of localized pain-sensory neurons by closely apposed blood vessels. We examined this presumption more closely by simultaneously recording the subjective report of the throbbing rhythm and the arterial pulse in human subjects of either sex with throbbing dental pain-a prevalent condition whose pulsatile quality is widely regarded a primary sensation. Contrary to the generally accepted view, which would predict a direct correspondence between the two, we found that the throbbing rate (44 bpm ± 3 SEM) was much slower than the arterial pulsation rate (73 bpm ± 2 SEM, p < 0.001), and that the two rhythms exhibited no underlying synchrony. Moreover, the beat-to-beat variation in arterial and throbbing events observed distinct fractal properties, indicating that the physiological mechanisms underlying these rhythmic events are distinct. Confirmation of the generality of this observation in other pain conditions would support an alternative hypothesis that the throbbing quality is not a primary sensation but rather an emergent property, or perception, whose "pacemaker" lies within the CNS. Future studies leading to an improved understanding of the neurobiological basis of clinically relevant pain qualities, such as throbbing, will also enhance our ability to measure and therapeutically target severe and disabling pain.
Input impedance is the frequency-dependent afterload to pulsatile blood flow. Studies of input impedance have been performed as early as the 1960s and have been applied to hypertension (HTN). However, to date, these studies have not been systematically evaluated. This systematic review aims to summarize the literature, interpret existing data from the perspective of impedance theory, and to discuss their potential for generating physiological insights into HTN.
Virtually everyone can recall an experience, migraine or not, in which pain had a throbbing, pulsatile quality, particularly in association with intense pain. Its pulsatile character strongly reinforces the common presumption that it coincides with the heartbeat. For migraine, a cerebral vascular origin of the throbbing quality is a central tenet of the prevailing scientific view of migraine pain. However, recent data challenge this perspective, with implications for our understanding of throbbing pain not only for migraine but also for the pathophysiology of throbbing pain in other conditions as well.
Much research in migraine focuses on understanding its initiation. But as migraine is typically self-limited, its offset may be as important as its onset. We pose the question "how does migraine stop?" to three investigators with different backgrounds. The consensus is that the termination of a migraine attack, rather than being the passive loss of a trigger, must itself be an active biologic process.
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