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The VLPFC vs. the DLPFC in down-regulating social pain using reappraisal and distraction strategies.

The dorsolateral (DLPFC) and ventrolateral prefrontal cortices (VLPFC) are both crucial structures involved in voluntary emotional regulation. However, it remains unclear whether the functions of these two cortical regions that are involved in emotional regulation-which are usually active in non-social situations-could be generalized to the regulation of social pain as well. This study employed transcranial magnetic stimulation (TMS) to examine the causal relationship between the DLPFC/VLPFC and the emotional regulation of social pain via distraction and reappraisal. Ninety human participants (45 males and 45 females) initially underwent either active (DLPFC/VLPFC, n = 30/30) or sham (vertex, n = 30) TMS sessions. Participants were then instructed to use both distraction and reappraisal strategies to down-regulate any negative emotions evoked by social exclusion pictures. Convergent results of the subjective emotional rating and electrophysiological indices demonstrated that: 1) both the DLPFC and VLPFC highly facilitate the down-regulation of affective responses caused by social exclusion, revealing a causal role of these lateral prefrontal cortices in voluntary emotional regulation of both non-social and social pain; and 2) these two cortical regions showed relative functional specificity for distraction (DLPFC) and reappraisal (VLPFC) strategies, which helps to refine the cortical targeting of therapeutic protocols. In addition, the TMS effect was sustainable for at least one hour, showcasing the potential feasibility of using this method in clinical practice. Together, these findings provide cognitive and neural evidence for the targeting of the VLPFC and/or the DLPFC to improve emotional regulation abilities, especially in social contexts.This study aimed to examine the role of the dorsolateral and ventrolateral prefrontal cortices in emotional regulation, particularly in response to social pain through the use of distraction and reappraisal strategies, as this is a relatively underexplored area of inquiry. This study makes a significant contribution to the literature because our results provide novel empirical information on the role of these cortical structures in the processing of negative emotions elicited within certain social contexts. As such, our findings have potential clinical implications, paving the way for future clinicians to be able to accurately target specific brain regions among patients struggling with impaired social cognition abilities, including those diagnosed with post-traumatic stress disorder, autism spectrum disorder, social anxiety disorder, and depression.

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Toll-like receptor 2 and 4 antagonism for the treatment of experimental autoimmune encephalitis (EAE)-related pain.

Neuropathic pain is a major symptom of multiple sclerosis (MS) with up to 92% of patients reporting bodily pain, and 85% reporting pain severe enough to cause functional disability. None of the available therapeutics target MS pain. Toll-like receptors 2 and 4 (TLR2/TLR4) have emerged as targets for treating a wide array of autoimmune disorders, including MS, as well as having demonstrated success at suppressing pain in diverse animal models. The current series of studies tested systemic TLR2/TLR4 antagonists in males and females in a low-dose myelin oligodendrocyte glycoprotein (MOG) experimental autoimmune encephalitis (EAE) model, with reduced motor dysfunction to allow unconfounded testing of allodynia through 50+ days post-MOG. The data demonstrated that blocking TLR2/TLR4 suppressed EAE-related pain, equally in males and females; upregulation of dorsal spinal cord proinflammatory gene expression for TLR2, TLR4, NLRP3, interleukin-1β, IkBα, TNF-α and interleukin-17; and upregulation of dorsal spinal cord expression of glial immunoreactivity markers. In support of these results, intrathecal interleukin-1 receptor antagonist reversed EAE-induced allodynia, both early and late after EAE induction. In contrast, blocking TLR2/TLR4 did not suppress EAE-induced motor disturbances induced by a higher MOG dose. These data suggest that blocking TLR2/TLR4 prevents the production of proinflammatory factors involved in low dose EAE pathology. Moreover, in this EAE model, TLR antagonists were highly effective in reducing pain, whereas motor impairment, as seen in high dose MOG EAE, is not affected.

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Tick peptides evoke itch by activating MrgprC11/X1 to sensitize TRPV1 in pruriceptors.

Tick bites severely threaten human health because they allow the transmission of many deadly pathogens, including viruses, bacteria, protozoa and helminths. Pruritus is a leading symptom of tick bites, but its molecular and neural bases remain elusive.

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The prevalence and impact of migraine and severe headache in the United States: Updated age, sex, and socioeconomic-specific estimates from government health surveys.

Accurate, up-to-date estimates of the burden of migraine and severe headache are important for evidence-based decision-making about workforce needs and the distribution of health resources. We used data from US government health surveys to report the prevalence, trends, and impact of this condition by age, sex, and poverty status.

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Prospective cohort study of routine exercise and headache outcomes among adults with episodic migraine.

To evaluate the association of routine exercise with headache frequency, intensity, and duration among adults with episodic migraine (EM).

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Remote electrical neuromodulation for acute treatment of migraine in adolescents.

Migraine is a common disabling neurological disorder. Current acute treatments for migraine in adolescents are mostly pharmacological and may have limited effectiveness, can cause side effects, and may lead to medication overuse. There is an unmet need for effective and well-tolerated treatments. Remote electrical neuromodulation (REN) is a novel acute treatment of migraine that stimulates upper arm peripheral nerves to induce conditioned pain modulation (CPM)-an endogenous analgesic mechanism. The REN device (Nerivio , Theranica Bio-Electronics Ltd., Israel) is a FDA-authorized device for acute treatment of migraine in adults. This study assessed the efficacy and safety of REN in adolescents with migraine.

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Skin-Nerve Co-culture Systems for Disease Modeling and Drug Discovery.

Prominent clinical problems related to the skin-nerve interface include barrier dysfunction and erythema but it is the symptoms of pain and itch that lead patients to seek medical treatment. Tissue-engineered innervated skin models provide an excellent solution for studying the mechanisms underlying neuro-cutaneous disorders for drug screening, and cutaneous device development. Innervated skin substitutes provide solutions to the traditional monolayer cultures and have advantages that make them preferable to animal studies for certain applications, such as measuring somatosensation. The tissue-engineered innervated skin models replicate the complex stratified epidermis that provides barrier function in native skin, a feature that is lacking in monolayer co-cultures, while allowing for measurement of nerve function that cannot be achieved in animal models. In this review, the advantages and disadvantages of different cell sources and scaffold materials will be discussed and a presentation of the current state of the field is reviewed.

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Does Pollen Trigger Urologic Chronic Pelvic Pain Syndrome Flares? A Case-Crossover Analysis in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network.

To determine whether pollen triggers urologic chronic pelvic pain syndrome (UCPPS) flares.

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Cumulative Lifetime Violence Severity and Chronic Pain in a Community Sample of Canadian Men.

To create a descriptive profile of chronic pain severity in men with lifetime cumulative violence histories, as a target and/or a perpetrator, and investigate how chronic pain severity is associated with and predicted by lifetime cumulative violence severity and known determinants of chronic pain.

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Structural and functional brain abnormalities in postherpetic neuralgia: a systematic review of neuroimaging studies.

In recent decades, an increasing number of neuroimaging studies utilizing magnetic resonance imaging (MRI) have explored the differential effects of postherpetic neuralgia (PHN) on brain structure and function. We systematically reviewed and integrated the findings from relevant neuroimaging studies in PHN patients. A total of 15 studies with 16 datasets were ultimately included in the present study, which were categorized by the different neuroimaging modalities. The results revealed that PHN was closely associated with structural/microstructural and functional abnormalities of the brain mainly located in the 'pain matrix', including the thalamus, insula, parahippocampus, amygdala, dorsolateral prefrontal cortex, precentral gyrus and inferior parietal lobe, as well as other regions, such as the precuneus, lentiform nucleus and brainstem. Furthermore, a disruption of multiple networks, including the default-mode network, salience network and limbic system, may contribute to the neurophysiological mechanisms underlying PHN. The findings indicate that the cerebral abnormalities of PHN were not restricted to the pain matrix but extended to other regions, profoundly affecting the regulation and moderation of pain processing in PHN. Future prospective and longitudinal neuroimaging studies with larger samples will elucidate the progressive trajectory of neural changes in the pathophysiological process of PHN.

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