Paracrine relationship between incretin hormones and endogenous 5-hydroxytryptamine in the small and large intestine.

Background: Enterochromaffin (EC) cell-derived 5-hydroxytryptamine (5-HT) is a mediator of toxin-induced reflexes, initiating emesis via vagal and central 5-HT receptors. The amine is also involved in gastrointestinal (GI) reflexes that are prosecretory and promotile, and recently 5-HT's roles in chemosensation in the distal bowel have been described. We set out to establish the efficacy of 5-HT signaling, local 5-HT levels and pharmacology in discrete regions of the mouse small and large intestine.

Habituation deficit of visual evoked potentials in migraine patients with hypermobile Ehlers-Danlos syndrome.

Objectives: Migraine is one of the most frequent clinical manifestations of hypermobile Ehlers-Danlos syndrome (hEDS). The comorbidity between these two diseases has been only partially investigated. We aimed to observe whether neurophysiological alterations described in migraineurs in visual evoked potentials (VEPs) were present in hEDS patients with migraine.

Effectiveness and safety profile of greater occipital nerve blockade in cluster headache: a systematic review.

Background: Greater occipital nerve (GON) blockade is a short-term preventive therapy for cluster headache (CH). We conducted a systematic review to evaluate the effectiveness and safety of GON blockade in patients with CH.

Methods: On 23 October 2020, we searched MEDLINE, Embase, Embase Classic, PsycINFO, CINAHL, CENTRAL and Web of Science databases from their inception date.

An evaluation of the role of miR-361-5p in senescence and systemic ageing.

Senescent cells are key regulators of ageing and age-associated disease. MicroRNAs (miRs) are a key component of the molecular machinery governing cellular senescence, with several known to regulate important genes associated with this process. We sought to identify miRs associated with both senescence and reversal by pinpointing those showing opposing directionality of effect in senescence and in response to senotherapy.

Primary headache epidemiology in children and adolescents: a systematic review and meta-analysis.

Introduction: Headache is the most prevalent neurological manifestation in adults and one of the leading causes of disability worldwide. In children and adolescents, headaches are arguably responsible for a remarkable impact on physical and psychological issues, yet high-quality evidence is scarce.

Material And Methods: We searched cross-sectional and cohort studies in Embase, Medline, Web of Science, and Cochrane databases from January 1988 to June 2022 to identify the prevalence of headaches in 8-18 years old individuals.

Transient receptor potential Ankyrin-1 (TRPA1) agonists suppress myelination and induce demyelination in organotypic cortical slices.

Oligodendrocytes are highly specialized glial cells characterized by their production of multilayer myelin sheaths that wrap axons to speed up action potential propagation. It is due to their specific role in supporting axons that impairment of myelin structure and function leads to debilitating symptoms in a wide range of degenerative diseases, including Multiple Sclerosis and Leukodystrophies. It is known that myelin damage can be receptor-mediated and recently oligodendrocytes have been shown to express Ca -permeable Transient Receptor Potential Ankyrin-1 (TRPA1) channels, whose activation can result in myelin damage in ischemia.

Enrichment of human embryonic stem cell-derived V3 interneurons using an Nkx2-2 gene-specific reporter.

V3 spinal interneurons are a key element of the spinal circuits, which control motor function. However, to date, there are no effective ways of deriving a pure V3 population from human pluripotent stem cells. Here, we report a method for differentiation and isolation of spinal V3 interneurons, combining extrinsic factor-mediated differentiation and magnetic activated cell sorting.

HCN2 Ion Channels Drive Pain in Rodent Models of Migraine.

Migraine is believed to be initiated by neuronal activity in the CNS, that triggers excitation of nociceptive trigeminal ganglion (TG) nerve fibers innervating the meninges and thus causes a unilateral throbbing headache. Drugs that precipitate or potentiate migraine are known to elevate intracellular levels of the cyclic nucleotides cAMP or cGMP, while anti-migraine treatments couple to signaling pathways that reduce cAMP or cGMP, suggesting an involvement of these cyclic nucleotides in migraine. Members of the HCN ion channel family are activated by direct binding of cAMP or cGMP, suggesting in turn that a member of this family may be a critical trigger of migraine.

STIM1 and ORAI1 form a novel cold transduction mechanism in sensory and sympathetic neurons.

Moderate coolness is sensed by TRPM8 ion channels in peripheral sensory nerves, but the mechanism by which noxious cold is detected remains elusive. Here, we show that somatosensory and sympathetic neurons express two distinct mechanisms to detect noxious cold. In the first, inhibition by cold of a background outward current causes membrane depolarization that activates an inward current through voltage-dependent calcium (Ca ) channels.

Delayed viral vector mediated delivery of neurotrophin-3 improves skilled hindlimb function and stability after thoracic contusion.

Intramuscular injection of an Adeno-associated viral vector serotype 1 (AAV1) encoding Neurotrophin-3 (NT3) into hindlimb muscles 24 h after a severe T9 spinal level contusion in rats has been shown to induce lumbar spinal neuroplasticity, partially restore locomotive function and reduce spasms during swimming. Here we investigate whether a targeted delivery of NT3 to lumbar and thoracic motor neurons 48 h following a severe contusive injury aids locomotive recovery in rats. AAV1-NT3 was injected bilaterally into the tibialis anterior, gastrocnemius and rectus abdominus muscles 48-h following trauma, persistently elevating serum levels of the neurotrophin.

CD206/MHCII macrophage accumulation at nerve injury site correlates with attenuation of allodynia in TASTPM mouse model of Alzheimer's disease.

Chronic pain is undertreated in people with Alzheimer's disease (AD) and better understanding of the underlying mechanisms of chronic pain in this neurodegenerative disease is essential. Neuropathic pain and AD share a significant involvement of the peripheral immune system. Therefore, we examined the development of nerve injury-induced allodynia in TASTPM (APPsweXPS1.

Temperature-dependent structural plasticity of hippocampal synapses.

The function of the central nervous system (CNS) is strongly affected by temperature. However, the underlying processes remain poorly understood. Here, we show that hypothermia and hyperthermia trigger bidirectional re-organization of presynaptic architecture in hippocampal neurons, resulting in synaptic strengthening, and weakening, respectively.

Microglia states and nomenclature: A field at its crossroads.

Microglial research has advanced considerably in recent decades yet has been constrained by a rolling series of dichotomies such as "resting versus activated" and "M1 versus M2." This dualistic classification of good or bad microglia is inconsistent with the wide repertoire of microglial states and functions in development, plasticity, aging, and diseases that were elucidated in recent years. New designations continuously arising in an attempt to describe the different microglial states, notably defined using transcriptomics and proteomics, may easily lead to a misleading, although unintentional, coupling of categories and functions.

Recent Advances and Updates in Trigeminal Autonomic Cephalalgias.

Trigeminal autonomic cephalalgias (TACs) are discrete primary headache disorders, characterized by severe unilateral head pain, typically trigeminal distribution, with ipsilateral cranial autonomic symptoms. The conditions within this group are hemicrania continua, cluster headache, paroxysmal hemicrania, and short-lasting unilateral neuralgiform headache with conjunctival injection and tearing and short-lasting unilateral neuralgiform headache with autonomic symptoms. Several advances have been made in understanding the pathogenesis and evolving treatment options in TACs.

Proinflammatory profile in the skin of Parkinson's disease patients with and without pain.

Background: Pain is a common non-motor symptom of Parkinson`s disease (PD), however, its pathomechanism remains elusive.

Objective: We aimed to investigate the local gene expression of selected proinflammatory mediators in patients with PD and correlated our data with patients`pain phenotype.

Methods: We recruited 30 patients with PD and 30 healthy controls.

Blinding and sham control methods in trials of physical, psychological, and self-management interventions for pain (article II): a meta-analysis relating methods to trial results.

Sham interventions in randomized clinical trials (RCTs) of physical, psychological, and self-management (PPS) therapies for pain are highly variable in design and believed to contribute to poor internal validity. However, it has not been formally tested whether the extent to which sham controls resemble the treatment under investigation consistently affects trial outcomes, such as effect sizes, differential attrition, participant expectancy, and blinding effectiveness. Placebo- or sham-controlled RCTs of PPS interventions of clinical pain populations were searched in 12 databases.

Angiotensin type 2 receptor antagonism as a new target to manage gout.

Background: There is a growing search for therapeutic targets in the treatment of gout. The present study aimed to evaluate the analgesic and anti-inflammatory potential of angiotensin type 2 receptor (ATR) antagonism in an acute gout attack mouse model.

Methods: Male wild-type (WT) C57BL/6 mice either with the ATR antagonist, PD123319 (10 pmol/joint), or with vehicle injections, or ATR KO mice, received intra-articular (IA) injection of monosodium urate (MSU) crystals (100 µg/joint), that induce the acute gout attack, and were tested for mechanical allodynia, thermal hyperalgesia, spontaneous nociception and ankle edema development at several times after the injections.

DNA methylation signatures of Alzheimer's disease neuropathology in the cortex are primarily driven by variation in non-neuronal cell-types.

Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by the progressive accumulation of amyloid-beta and neurofibrillary tangles of tau in the neocortex. We profiled DNA methylation in two regions of the cortex from 631 donors, performing an epigenome-wide association study of multiple measures of AD neuropathology. We meta-analyzed our results with those from previous studies of DNA methylation in AD cortex (total n = 2013 donors), identifying 334 cortical differentially methylated positions (DMPs) associated with AD pathology including methylomic variation at loci not previously implicated in dementia.

Dorsal root ganglia CX3CR1 expressing monocytes/macrophages contribute to arthritis pain.

Pain is a persistent symptom of Rheumatoid Arthritis, and the K/BxN serum transfer model recapitulates both association and dissociation between pain and joint inflammation in RA. Furthermore, this model features monocyte/macrophage infiltration in joints and lumbar dorsal root ganglia (DRG), where these immune cells are close to nociceptive neurons. We focussed on CXCR-monocyte/macrophage trafficking and show that at peak paw swelling associated with nociception, CXCR deletion altered neither swelling nor macrophage infiltration/phenotype in paws.