Neural plasticity in common forms of chronic headaches

Headaches are universal experiences and among the most common disorders. While headache may be physiological in the acute setting, it can become a pathological and persistent condition.The mechanisms underlying the transition from episodic to chronic pain have been the subject of intense study. Using physiological and imaging methods, researchers have identified a number of different forms of neural plasticity associated with migraine and other headaches, including peripheral and central sensitization, and alterations in the endogenous mechanisms of pain modulation. While these changes have been proposed to contribute to headache and pain chronification, some findings are likely the results of repetitive noxious stimulation, such as atrophy of brain areas involved in pain perception and modulation. In this review, we provide a narrative overview of recent advances on the neuroimaging, electrophysiological and genetic aspects of neural plasticity associated with the most common forms of chronic headaches, including migraine, cluster headache, tension-type headache, and medication overuse headache

Using stratified medicine to understand, diagnose, and treat neuropathic pain

Neuropathic pain (NeuP) is defined as pain arising from a lesion or disease of the somatosensory nervous system. NeuP is common, affecting approximately 6-8% of the general population and currently treatment is inadequate due to both poor drug efficacy and tolerability. Many different types of injury can cause neuropathic pain including genetic (e.g. SCN9A gain of function variants), metabolic (e.g. diabetic polyneuropathy), infective (e.g. HIV associated neuropathy, hepatitis), traumatic and toxic (e.g. chemotherapy induced neuropathy) causes. Such injurious events can impact on anatomically distinct regions of the somatosensory nervous system ranging from the terminals of nociceptive afferents (in small fiber neuropathy) to the thalamus (in post-stroke pain). Classification of neuropathic pain using etiology and location remains an important aspect of routine clinical practice; however, pain medicine is coming to the realization that we need more precision in this classification. The hope is that improved classification will lead to better understanding of risk, prognosis and optimal treatment of NeuP

Fibromyalgia: A Unifying Neuroendocrinologic Model for Understanding Its Pathophysiology

Fibromyalgia is believed to affect at least 2% of the population. Despite advances in the scientific understanding of the derangements of central and peripheral pain processing mechanisms in fibromyalgia, no current models of its pathophysiology account for the other clinical conditions associated with it such as fatigue, migraine headache, irritable bowel syndrome, and sleep cycle abnormalities. A neuroendocrinologic model of fibromyalgia is presented that accommodates both its known central and peripheral pain mechanisms as well as the myriad of hormonal, visceral, and psychological symptoms associated with that disorder. This model also provides a unifying pathophysiologic basis of fibromyalgia and chronic muscle pain, and offers the potential for developing new avenues of research and treatment for these enigmatic, frequently disabling medical conditions

Does conservative treatment change the brain in patients with chronic musculoskeletal pain? : a systematic review

Background: Chronic musculoskeletal pain is characterized by maladaptive central neuroplastic changes. Many observational studies have demonstrated that chronic pain states are associated with brain alterations regarding structure and/or function. Rehabilitation of patients with chronic musculoskeletal pain may include cognitive, exercise, or multimodal therapies. Objective: The current review aims to provide a constructive overview of the existing literature reporting neural correlates, based on brain magnetic resonance imaging (MRI) techniques, following conservative treatment in chronic musculoskeletal pain patients. Study Design: Systematic review of the literature. Methods: The current review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Literature was searched from 3 databases and screened for eligibility. Methodological quality across studies was assessed with Cochrane Collaboration's tool for assessing risk of bias and quality of evidence was determined applying the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. Results: A total of 9 eligible studies were identified with a predominant high risk of bias. Cognitive behavioral therapy induced several structural and functional changes predominantly in prefrontal cortical regions and a shift from affective to sensory-discriminative brain activity after behavioral extinction training. Multidisciplinary treatment in pediatric complex regional pain syndrome facilitated normalization of functional connectivity of resting-state networks and the amygdala, and increased gray matter in prefrontal and specific subcortical areas. Exercise therapy led to specific for resting-state functional connectivity and a trend towards pressure-induced brain activity changes. Limitations: A very small number of studies was available, which furthermore exhibited small study samples. Moreover, only 2 of the included studies were randomized controlled trials. Conclusions: It is likely that conservative treatments may induce mainly functional and structural brain changes in prefrontal regions in patients with chronic musculoskeletal pain. Due to the relatively high risk of bias across the included studies, future studies with randomized designs are needed to confirm the current findings. In addition, more research evaluating

Vicarious experiences and detection accuracy while observing pain and touch: the effect of perspective taking

In this study, we investigated the effects of observing pain and touch in others on vicarious somatosensory experiences and the detection of subtle somatosensory stimuli. Furthermore, the effect of taking a first- versus a third-person perspective was investigated. Undergraduates (N = 57) viewed videos depicting hands being pricked (pain), hands being touched by a cotton swab (touch), and control scenes (same approaching movement of a hand as in the other video categories, but without the painful/touching object) while experiencing vibrotactile stimuli themselves on the left, on the right, or on both hands. Participants reported the location at which they felt a somatosensory stimulus. The vibrotactile stimuli and visual scenes were applied in a spatially congruent or incongruent way, and other trials were presented without vibrotactile stimuli. The videos were depicted in first-person perspective and third-person perspective (i.e., the videos were shown upside down). We calculated the proportions of correct responses and false alarms (i.e., numbers of trials on which a vicarious somatosensory experience was reported congruent or incongruent to the site of the visual information). Pain-related scenes facilitated the detection of tactile stimuli and augmented the number of vicarious somatosensory experiences, as compared with observing the touch or control videos. Detection accuracy was higher for videos depicted in first-person perspective than for those in third-person perspective. Perspective had no effect on the number of vicarious somatosensory experiences. This study indicates that somatosensory detection is particularly enhanced during the observation of pain-related scenes, as compared to the observation of touch or control videos. These research findings further demonstrate that perspective taking impacts somatosensory detection, but not the report of vicarious experiences

The Somatosensory Link in Fibromyalgia: Functional Connectivity of the Primary Somatosensory Cortex Is Altered by Sustained Pain and Is Associated With Clinical/Autonomic Dysfunction

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111091/1/art39043.pd

The neural mechanisms of mindfulness-based pain relief: a functional magnetic resonance imaging-based review and primer.

The advent of neuroimaging methodologies, such as functional magnetic resonance imaging (fMRI), has significantly advanced our understanding of the neurophysiological processes supporting a wide spectrum of mind-body approaches to treat pain. A promising self-regulatory practice, mindfulness meditation, reliably alleviates experimentally induced and clinical pain. Yet, the neural mechanisms supporting mindfulness-based pain relief remain poorly characterized. The present review delineates evidence from a spectrum of fMRI studies showing that the neural mechanisms supporting mindfulness-induced pain attenuation differ across varying levels of meditative experience. After brief mindfulness-based mental training (ie, less than 10 hours of practice), mindfulness-based pain relief is associated with higher order (orbitofrontal cortex and rostral anterior cingulate cortex) regulation of low-level nociceptive neural targets (thalamus and primary somatosensory cortex), suggesting an engagement of unique, reappraisal mechanisms. By contrast, mindfulness-based pain relief after extensive training (greater than 1000 hours of practice) is associated with deactivation of prefrontal and greater activation of somatosensory cortical regions, demonstrating an ability to reduce appraisals of arising sensory events. We also describe recent findings showing that higher levels of dispositional mindfulness, in meditation-naïve individuals, are associated with lower pain and greater deactivation of the posterior cingulate cortex, a neural mechanism implicated in self-referential processes. A brief fMRI primer is presented describing appropriate steps and considerations to conduct studies combining mindfulness, pain, and fMRI. We postulate that the identification of the active analgesic neural substrates involved in mindfulness can be used to inform the development and optimization of behavioral therapies to specifically target pain, an important consideration for the ongoing opioid and chronic pain epidemic

Exercise Increases Pressure Pain Tolerance but Not Pressure and Heat Pain Thresholds in Healthy Young Men

Background: Exercise causes an acute decrease in the pain sensitivity known as exercise-induced hypoalgesia (EIH), but the specificity to certain pain modalities remains unknown. This study aimed to compare the effect of isometric exercise on the heat and pressure pain sensitivity. Methods: On three different days, 20 healthy young men performed two submaximal isometric knee extensions (30% maximal voluntary contraction in 3 min) and a control condition (quiet rest). Before and immediately after exercise and rest, the sensitivity to heat pain and pressure pain was assessed in randomized and counterbalanced order. Cuff pressure pain threshold (cPPT) and pain tolerance (cPTT) were assessed on the ipsilateral lower leg by computer-controlled cuff algometry. Heat pain threshold (HPT) was recorded on the ipsilateral foot by a computer-controlled thermal stimulator. Results: Cuff pressure pain tolerance was significantly increased after exercise compared with baseline and rest (p \u3c 0.05). Compared with rest, cPPT and HPT were not significantly increased by exercise. No significant correlation between exercise-induced changes in HPT and cPPT was found. Test–retest reliability before and after the rest condition was better for cPPT and CPTT (intraclass correlation \u3e 0.77) compared with HPT (intraclass correlation = 0.54). Conclusions: The results indicate that hypoalgesia after submaximal isometric exercise is primarily affecting tolerance of pressure pain compared with the pain threshold. These data contribute to the understanding of how isometric exercise influences pain perception, which is necessary to optimize the clinical utility of exercise in management of chronic pain. Significance: The effect of isometric exercise on pain tolerance may be relevant for patients in chronic musculoskeletal pain as a pain-coping strategy. What does this study add? The results indicate that hypoalgesia after submaximal isometric exercise is primarily affecting tolerance of pressure pain compared with the heat and pressure pain threshold. These data contribute to the understanding of how isometric exercise influences pain perception, which is necessary to optimize the clinical utility of exercise in management of chronic pain

Distinctive alterations in the functional anatomy of the cerebral cortex in pain-sensitized osteoarthritis and fibromyalgia patients

Pain-sensitized osteoarthritis and fibromyalgia patients characteristically show nociceptive system augmented responsiveness as a common feature. However, sensitization can be originally related to the peripheral injury in osteoarthritis patients, whereas pain and bodily discomfort spontaneously occur in fibromyalgia with no apparent origin. We investigated the distinct functional repercussion of pain sensitization in the cerebral cortex in both conditions. Thirty-one pain-sensitized knee osteoarthritis patients and 38 fibromyalgia patients were compared with matched control groups. And new samples of 34 sensitized knee osteoarthritis and 63 fibromyalgia patients were used to directly compare each condition. A combined measure of local functional connectivity was estimated to map functional alterations in the cerebral cortex at rest. In osteoarthritis, weaker local connectivity was identified in the insula, which is a cortical area processing important aspects of the brain response to painful stimulation. In contrast, fibromyalgia patients showed weaker connectivity in the sensorimotor cortex extensively affecting the cortical representation of the body. In osteoarthritis, weaker insular cortex connectivity is compatible with reduced neural activity during metabolic recovery after repeated activation. In the fibromyalgia neurophysiological context, weaker connectivity may better express both reduced neural activity and increased excitability, particularly affecting the sensorimotor cortex in patients with spontaneous body pain. Such a combination is compatible with a central gain enhancement mechanism, where low sensory tolerance results from the over-amplification of central sensory reception to compensate a presumably weak sensory input. We propose that deficient proprioception could be a factor contributing to weak sensory input. The online version contains supplementary material available at 10.1186/s13075-022-02942-3

Disrupted Brain Circuitry for Pain‐Related Reward/Punishment in Fibromyalgia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102040/1/art38191.pd