Somatotopic organization of brainstem analgesic circuitry.

The lateral periaqueductal gray (lPAG) evokes somatotopically appropriate defensive behaviors, including an analgesia that allows the animal to escape or fight unimpeded. Whether the lPAG and its descending targets are also able to drive somatotopically specific analgesic responses is not known. In this work, we performed ultrahigh-field functional magnetic resonance imaging of the lPAG in 93 participants during a placebo analgesia paradigm performed at different body locations.

Investigating the Modulation of Corticomotor and Neuromuscular Function by Contralateral and Ipsilateral Experimental Pain Applied During Cycling.

Pain can impair exercise performance, but its influence on motor control, in particular the effect of robust experimental pain on the timecourse of corticomotor responses throughout prolonged, exhaustive cycling, remains unclear. We tested the hypothesis that an augmented experimental pain intervention applied to exercising and non-exercising limbs would modulate neuromuscular function, corticospinal excitability and inhibition, and exacerbate perceptual and cardiorespiratory responses to exercise. Ten healthy adults (two females) completed three single-leg cycling sessions at 60% peak power output to failure: without experimental pain (CTRL), with intermittent occlusions applied to the resting leg (CONTRA), and with occlusions upon the exercising leg (IPSI).

Pain in Parkinson's disease is impacted by motor complications, anxiety and sleep disturbances.

Background: Parkinson's disease (PD) is the second most common neurodegenerative disease. Over two thirds of People with Parkinson's (PwP) live with chronic PD-related pain, but its successful management remains an unmet need. Unrevealing links between pain and other motor and non-motor symptoms (NMS) of PD may accelerate delivery of much needed precision pain medicine approaches for PwP.

Advances in diagnosis, classification, and management of pain in Parkinson's disease.

With over 10 million people affected worldwide, Parkinson's disease is the fastest-growing neurological disorder. More than two-thirds of people with Parkinson's disease live with chronic pain, which can manifest in various stages of the disease, substantially affecting daily activities and quality of life. The Parkinson's disease Pain Classification System overcomes the limitations of previous classification systems by distinguishing between pain related to Parkinson's disease and unrelated pain, while also incorporating clinical and pathophysiological (mechanistic) descriptors such as nociceptive, neuropathic, and nociplastic pain.

A Parallel Human and Rat Investigation of the Interaction Between Descending and Spinal Modulatory Mechanisms.

Background: Healthy individuals demonstrate considerable heterogeneity upon dynamic quantitative sensory testing assessment of endogenous pain modulatory mechanisms. For those who stratify into a 'pro-nociceptive profile' cohort, consisting of inefficient conditioned pain modulation (CPM) and elevated temporal summation of pain (TSP), the optimal approach for balancing the net output of pain modulatory processes towards anti-nociception remains unresolved. In this translational healthy human and rat study, we examined whether descending modulation countered spinal amplification during concurrent application of a CPM and TSP paradigm alongside pupillometry since pontine activity was previously linked to functionality of endogenous pain modulatory mechanisms and pupil dilation.

Wearable devices may aid the recognition of fluctuation-related pain in Parkinson's disease-An exploratory, cross-sectional analysis of two prospective observational studies.

Fluctuation-related pain (FRP) affects more than one third of people with Parkinson's disease (PwP, PD) and has a harmful effect on health-related quality of life (HRQoL), but often remains under-reported by patients and neglected by clinicians. The National Institute for Health and Care Excellence (NICE) recommends The Parkinson KinetiGraphTM (the PKGTM) for remote monitoring of motor symptoms. We investigated potential links between the PKGTM-obtained parameters and clinical rating scores for FRP in PwP in an exploratory, cross-sectional analysis of two prospective studies: "The Non-motor International Longitudinal, Real-Life Study in PD-NILS" and "An observational-based registry of baseline PKG™ in PD-PKGReg".

A pain research strategy for Europe: A European survey and position paper of the European Pain Federation EFIC.

Background: Pain is the leading cause of disability and reduced quality of life worldwide. Despite the increasing burden for patients and healthcare systems, pain research remains underfunded and under focused. Having stakeholders identify and prioritize areas that need urgent attention in the field will help focus funding topics, reduce 'research waste', improve the effectiveness of pain research and therapy and promote the uptake of research evidence.

A role for leucine-rich, glioma inactivated 1 in regulating pain sensitivity.

Neuronal hyperexcitability is a key driver of persistent pain states, including neuropathic pain. Leucine-rich, glioma inactivated 1 (LGI1) is a secreted protein known to regulate excitability within the nervous system and is the target of autoantibodies from neuropathic pain patients. Therapies that block or reduce antibody levels are effective at relieving pain in these patients, suggesting that LGI1 has an important role in clinical pain.

An interdisciplinary perspective on peripheral drivers of pain in rheumatoid arthritis.

Pain is one of the most debilitating symptoms of rheumatoid arthritis (RA), and yet remains poorly understood, especially when pain occurs in the absence of synovitis. Without active inflammation, experts most often attribute joint pain to central nervous system dysfunction. However, advances in the past 5 years in both immunology and neuroscience research suggest that chronic pain in RA is also driven by a variety of abnormal interactions between peripheral neurons and mediators produced by resident cells in the local joint environment.

Pain in Multiple System Atrophy: A Community-Based Survey.

Background: Pain is a frequent yet poorly characterized symptom of multiple system atrophy (MSA). Understanding the factors influencing pain and its burden is crucial for improving the symptomatic treatment and quality of life of MSA individuals.

Objective: This study aimed at assessing the prevalence, characteristics, and current treatment strategies for pain in MSA.

A randomised controlled trial of the effect of intra-articular lidocaine on pain scores in inflammatory arthritis.

Chronic pain in inflammatory arthritis (IA) reflects a complex interplay between active disease in a peripheral joint and central pronociceptive mechanisms. Because intra-articular lidocaine may be used to abolish joint-specific peripheral input to the central nervous system, we aimed to validate its use as a clinical tool to identify those patients with IA whose pain likely incorporates centrally mediated mechanisms. We began by investigating whether there was a placebo response of intra-articular injection in patients with IA 1:1 randomised to receive intra-articular lidocaine or control (0.

Comparative analysis of centrally mediated and inflammatory pain experiences amongst patients diagnosed with rheumatoid arthritis: A multimethods study.

Background: The identification of pain originating from distinct biological processes may lead to individualised pain treatment. In this study, we aimed to explore the pain experiences of patients with rheumatoid arthritis (RA), differentiating between those predominantly exhibiting features of peripheral inflammatory versus centrally mediated pain.

Methods: Through a multimethods approach we (i) quantitatively analysed the differences in pain descriptors between patients diagnosed with RA experiencing peripheral inflammatory and centrally mediated pain, utilising the Short Form-McGill Pain Questionnaire which includes the pain visual analogue scale (VAS) and (ii) qualitatively explored their subjective pain experiences grounded in the biopsychosocial model, commonly applied in chronic pain.

Gastrointestinal pain: A systematic review of temporal summation of pain paradigms and outcomes.

Background And Objective: Since targeted treatment for gastrointestinal pain is elusive, identifying the mechanistic underpinning of this pain type is important. Facilitation of spinal neuronal responses underpins certain pain types, and the psychophysical temporal summation of pain (TSP) paradigm provides a proxy measure of spinal facilitatory processes. Our aim was to systematically review whether facilitated TSP is a feature of gastrointestinal pain in patients with, or pain-free people experiencing experimentally induced, gastrointestinal pain.

Deep sequencing of Phox2a nuclei reveals five classes of anterolateral system neurons.

The anterolateral system (ALS) is a major ascending pathway from the spinal cord that projects to multiple brain areas and underlies the perception of pain, itch, and skin temperature. Despite its importance, our understanding of this system has been hampered by the considerable functional and molecular diversity of its constituent cells. Here, we use fluorescence-activated cell sorting to isolate ALS neurons belonging to the Phox2a-lineage for single-nucleus RNA sequencing.

Psychological distress over 12 months post-diagnosis in an early inflammatory arthritis cohort.

Objectives: People with inflammatory arthritis (IA) experience worsened mental wellbeing alongside disease progression. Using the National Early Inflammatory Arthritis Audit (NEIAA), we assessed trends in psychological distress during the 12 months following IA diagnosis, mapping these against clinical outcomes to identify associations.

Methods: This is a prospective study of people recruited to NEIAA receiving an IA diagnosis and completing the baseline patient survey.

Setting the clinical context to non-motor symptoms reflected by Park-pain, Park-sleep, and Park-autonomic subtypes of Parkinson's disease.

Non-motor symptoms (NMS) of Parkinson's disease (PD) are well described in both clinical practice and the literature, enabling their management and enhancing our understanding of PD. NMS can dominate the clinical pictures and NMS subtypes have recently been proposed, initially based on clinical observations, and later confirmed in data driven analyses of large datasets and in biomarker-based studies. In this chapter, we provide an update on what is known about three common subtypes of NMS in PD.

Pain Science in Practice (Part 7):

Understanding the descending pain modulatory system allows for a neuroscientific explanation of naturally occurring pain relief. Evidence from basic science and clinical studies on the effectiveness of drugs in certain patient groups led to pharmacological manipulation of the descending pain modulatory system for analgesia. Understanding mechanisms and theories helps clinicians make sense of chronic musculoskeletal pain.

Pain Science in Practice (Part 6):

To understand the neuroscience of pain relief, one must know about the descending pain modulatory system. Neuronal pathways that originate in the brainstem and project to the spinal cord to modulate spinal neuronal activity provide a well-documented perspective on the mechanisms of analgesia that underpin pharmacological and nonpharmacological treatment options for people with musculoskeletal pain. Peripheral stimuli or signals from the cortex and subcortical regions of the brain can trigger the descending pain modulatory system (DPMS).

A back-translational study of descending interactions with the induction of hyperalgesia by high-frequency electrical stimulation in rats and humans.

In humans and animals, high-frequency electrocutaneous stimulation (HFS) induces an "early long-term potentiation-like" sensitisation, where synaptic plasticity is underpinned by an ill-defined interaction between peripheral input and central modulatory processes. The relative contributions of these processes to the initial pain or nociceptive response likely differ from those that underpin development of the heightened response. To investigate the impact of HFS-induced hyperalgesia on pain and nociception in perception and neural terms, respectively, and to explore the impact of descending inhibitory pathway activation on the development of HFS-induced hyperalgesia, we performed parallel studies utilising identical stimuli to apply HFS concurrent to (1) a conditioned pain modulation paradigm during psychophysical testing in healthy humans or (2) a diffuse noxious inhibitory controls paradigm during in vivo electrophysiological recording of spinal neurones in healthy anaesthetised rats.