Pain

Complex regional pain syndrome (CRPS) typically develops after fracture or trauma. Many of the studies so far have analyzed clinical and molecular markers of CRPS in comparison to healthy or pain controls. This approach, however, neglects mechanisms occurring during physiological trauma recovery. Therefore, we compared the clinical phenotype, sensory profiles, patients reported outcomes (PRO) and exosomal immunobarrier microRNAs (miRs) regulating barrier function and immune response between CRPS and fracture controls (FC) not fulfilling the CRPS diagnostic criteria...

Musculoskeletal pain is associated with altered motor control that despite short-term benefit, is hypothesised to have long-term consequences, contributing to the development of chronic pain. However, data on how motor control is altered when pain is sustained beyond a transient event are scarce. Here, we investigated motor adaptation, and its relationship to corticomotor excitability, in the transition to sustained muscle pain. Twenty-eight healthy individuals were injected with nerve growth factor (NGF) into the right extensor carpi radialis brevis (ECRB) muscle on Days 0 and 2...

Complex regional pain syndrome (CRPS) is a severely disabling disease characterized by pain, temperature changes, motor dysfunction and edema that most often occurs as an atypical response to a minor surgery or fracture. Inflammation involving activation and recruitment of innate immune cells, including both peripheral and central myeloid cells (i.e. macrophages and microglia, respectively), is a key feature of CRPS. However, the exact role and time-course of these cellular processes relative to the known acute and chronic phases of the disease are not fully understood...

Genetics studies on the placebo hypoalgesic effect highlight a promising link between single nucleotide polymorphisms (SNPs) in the dopamine, opioid, and endocannabinoid genes and placebo hypoalgesia. However, epistasis and replication studies are missing. In this study, we expanded upon previous findings related to the three SNPs in the opioid receptor mu subunit (OPRM1 rs1799971), catechol-O-methyltransferase (COMT rs4680), and fatty acid amide hydrolase (FAAH rs324420) genes associated with placebo hypoalgesia and tested the effect of a three-way interaction on placebo hypoalgesia...

Pain is a frequent and disabling symptom in multiple sclerosis (MS) patients; however, the underlying mechanisms of MS-related pain is not fully understood. Here, we demonstrated that cathepsin E (CatE) in neutrophils contributes to the generation of mechanical allodynia in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We showed that CatE-deficient (CatE) mice were highly resistant to myelin oligodendrocyte glycoprotein (MOG35-55)-induced mechanical allodynia. After MOG35-55 immunization, neutrophils immediately accumulated in the dorsal root ganglion (DRG)...

Pain and depressive mood commonly exhibit a comorbid relationship. Yet, the brain mechanisms that moderate the relationship between dysphoric mood and pain remain unknown. An exploratory analysis of fMRI, behavioral and psychophysical data was collected from a previous study in seventy-six healthy, non-depressed, and pain-free individuals. Participants completed the Beck Depression Inventory-II (BDI), a measure of negative mood/depressive symptomology and provided pain intensity and pain unpleasantness ratings in response to noxious heat (49°C) during perfusion-based, arterial spin labeled functional magnetic resonance imaging...

Neuropathic pain is frequently driven by ectopic impulse discharge (ectopia) generated in injured peripheral afferent neurons. Observations in the spinal nerve ligation (SNL) model in rats suggest that cell bodies in the dorsal root ganglion (DRG) contribute three times more to the ectopic barrage than the site of nerve injury (neuroma). The DRG is therefore a prime interventional target for pain control. Since DRG ectopia is selectively suppressed with lidocaine at concentrations too low to block axonal impulse propagation, we asked whether targeted delivery of dilute lidocaine to the L5 DRG can relieve L5 SNL-induced tactile allodynia without blocking normal sensation or motor function...

Hypersensitivity due to central pain mechanisms can influence recovery and lead to worse clinical outcomes, but the ability of quantitative sensory testing (QST), an index of sensitisation, to predict outcomes in chronic musculoskeletal disorders remains unclear. We systematically reviewed the evidence for ability of QST to predict pain, disability and negative affect using searches of CENTRAL, MEDLINE, EMBASE, AMED, CINAHL and PubMed databases up to April 2018. Title screening, data extraction, and methodological quality assessments were performed independently by 2 reviewers...

Sickle cell disease (SCD) is a medical condition in which chronic pain is common and negatively impacts psychosocial function and quality of life. While the brain mechanisms underlying chronic pain are well studied in other painful conditions, the brain mechanisms underlying chronic pain and the associated psychosocial comorbidities are not well established in SCD. A growing literature demonstrates the effect of treatment of chronic pain, including pharmacological and nonpharmacological treatments, on brain function...

Irritable bowel syndrome (IBS) is a visceral pain condition with psychological comorbidity. Brain imaging studies in IBS demonstrate altered function in anterior insula (aINS), a key hub for integration of interoceptive, affective and cognitive processes. However, alterations in aINS excitatory and inhibitory neurotransmission as putative biochemical underpinnings of these functional changes remain elusive. Using quantitative magnetic resonance spectroscopy (qMRS), we compared women with IBS and healthy women (HC) with respect to aINS glutamate+glutamine (Glx) and γ-aminobutyric acid (GABA+) concentrations and addressed possible associations with symptoms...

P2X4 is a ligand-gated ion channel implicated in neuropathic pain. Drug discovery efforts targeting P2X4 have been unsuccessful largely due to the difficulty in engineering specificity and selectivity. Here, we describe for the first time the generation of a panel of diverse monoclonal antibodies (mAbs) to human and mouse P2X4, capable of both positive and negative modulation of channel function. The affinity optimised anti-P2X4 mAb IgG#151-LO showed exquisite selectivity for human P2X4 and induced potent and complete block of P2X4 currents...

AbstarctPreviously, distinct sex differences were observed in the pronociceptive role of spinal immune cells in neuropathic and inflammatory mouse pain models. Both peripheral and central innate and adaptive immune changes contribute to sensitization in the tibia fracture rodent model of complex regional pain syndrome (CRPS), and the current study evaluated sex differences in the development of pronociceptive immune responses after fracture. At 4 and 7 weeks post fracture the analgesic effects of a microglia inhibitor were tested in male and female mice and PCR was used to measure inflammatory mediator expression in skin and spinal cord...

Migraine is a debilitating condition, however, the pharmacological effects on central nervous system networks following successful therapy is poorly understood. Defining this neurocircuitry is critical to our understanding of the disorder and for the development of anti-migraine drugs. Using an established inflammatory soup (IS) model of migraine-like pathophysiology (N=12) compared to sham synthetic interstitial fluid (SIF) migraine induction (N=12), our aim was to evaluate changes in network-level functional connectivity following sumatriptan-naproxen infusion in awake, conscious, rodents (Sprague-Dawley rats)...

No abstract text is available yet for this article.

In this clinical and neurophysiological study using a novel cold stimulator we aim at investigating whether cold evoked potentials may prove to be a reliable diagnostic tool to assess trigeminal small-fibre function.Using a novel device consisting of micro-Peltier elements, we recorded cold evoked potentials after stimulating the supraorbital and perioral regions and the hand dorsum in 15 healthy participants and in two patients with exemplary facial neuropathic pain conditions. We measured peripheral conduction velocity at the upper arm and studied the brain generators using source analysis...

The spinal grey matter region around the central canal, lamina X, is critically involved in somatosensory processing and visceral nociception. Although several classes of primary afferent fibers terminate or decussate in this area, little is known about organization and functional significance of the afferent supply of lamina X neurons. Using the hemisected ex-vivo spinal cord preparation, we show that virtually all lamina X neurons receive primary afferent inputs, which are predominantly mediated by the high-threshold Aδ fibers and C fibers...

Chronic widespread pain (CWP) is common and associated with loss of functioning and health. Subjects with chronic non-widespread pain (CnWP) are at increased risk of developing CWP, but few studies have described the nature of the development over time.We followed a random sample of 3105 participants from the population-based HUNT-3 study with five annual measurements of pain over four years. While 29% reported CWP on at least one occasion, only 7% reported it consistently on four or fsive occasions. The average annual cumulative incidence was 5% and the recovery rate was 38%...

Comorbidity of pain and posttraumatic stress disorder is well recognized but the reason for this association is unclear. This study investigated the direction of the relationship between pain and traumatic stress and the role that pain-related fear plays, for patients with acute whiplash associated disorder (WAD). Participants (n = 99) used an electronic diary to record hourly ratings of pain, traumatic stress and fear-of-pain symptoms over a day. Relationships between pain, traumatic stress and pain-related fear symptoms were investigated through multilevel models including variables lagged by one hour...

This study was performed to test whether the risk of developing chronic widespread pain (CWP) in those with regional pain was augmented in those with symptoms of neuropathic pain (NP). Persons free of CWP completed the Douleur Neuropathique 4 (scores ≥3 indicating NP); demographics; Hospital Anxiety and Depression scale; Pittsburgh Sleep Quality Index; and pain medications. Participants were classified as having no pain, regional pain with no symptoms of NP (NP-), or regional pain with symptoms of NP (NP)...

No abstract text is available yet for this article.