TAM receptors mediate the Fpr2-driven pain resolution and fibrinolysis after nerve injury.

Nerve injury causes neuropathic pain and multilevel nerve barrier disruption. Nerve barriers consist of perineurial, endothelial and myelin barriers. So far, it is unclear whether resealing nerve barriers fosters pain resolution and recovery.

Bone metabolism in complex regional pain syndrome.

Introduction: Patients with complex regional pain syndrome (CRPS) often show disturbed bone metabolism, assessed using three-phase bone scintigraphy (TPBS). However, current methods lack automation and standardisation. Bone serum markers have been proposed as biomarkers, but their utility is unclear.

Development and Evaluation of an MRI Artifact-Free Aneurysm Clip.

Background And Objectives: The digital subtraction angiography is still the gold standard in the follow-up after aneurysm surgery, although it remains a repeating invasive technique with accumulating X-ray exposure. An alternative magnetic resonance angiography has the disadvantage of metal-related artifacts. A metal-free aneurysm clip could overcome this problem.

Myelin barrier breakdown, mechanical hypersensitivity, and painfulness in polyneuropathy with claudin-12 deficiency.

Background: The blood-nerve and myelin barrier shield peripheral neurons and their axons. These barriers are sealed by tight junction proteins, which control the passage of potentially noxious molecules including proinflammatory cytokines via paracellular pathways. Peripheral nerve barrier breakdown occurs in various neuropathies, such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and traumatic neuropathy.

Molecular and clinical markers of pain relief in complex regional pain syndrome: An observational study.

Background: Complex regional pain syndrome (CRPS) is marked by disproportionate pain after trauma. Whilst the long-term outcome is crucial to patients, predictors or biomarkers of the course of pain or CRPS symptoms are still lacking. In particular, microRNAs, such as miR-223, decreased in CRPS, have been described only in cross-sectional studies.

Selective blood-nerve barrier leakiness with claudin-1 and vessel-associated macrophage loss in diabetic polyneuropathy.

Diabetic polyneuropathy (DPN) is the most common complication in diabetes and can be painful in up to 26% of all diabetic patients. Peripheral nerves are shielded by the blood-nerve barrier (BNB) consisting of the perineurium and endoneurial vessels. So far, there are conflicting results regarding the role and function of the BNB in the pathophysiology of DPN.

Pain Control by Targeting Oxidized Phospholipids: Functions, Mechanisms, Perspectives.

Within the lipidome oxidized phospholipids (OxPL) form a class of chemically highly reactive metabolites. OxPL are acutely produced in inflamed tissue and act as endogenous, proalgesic (pain-inducing) metabolites. They excite sensory, nociceptive neurons by activating transient receptor potential ion channels, specifically TRPA1 and TRPV1.

COVID-19 Induced Acute Respiratory Distress Syndrome-A Multicenter Observational Study.

Proportions of patients dying from the coronavirus disease-19 (COVID-19) vary between different countries. We report the characteristics; clinical course and outcome of patients requiring intensive care due to COVID-19 induced acute respiratory distress syndrome (ARDS). This is a retrospective, observational multicentre study in five German secondary or tertiary care hospitals.

Stabilization of Delphinidin in Complex with Sulfobutylether-β-Cyclodextrin Allows for Antinociception in Inflammatory Pain.

Delphinidin (DEL) is a plant-derived antioxidant with clinical potential to treat inflammatory pain but suffers from poor solubility and low bioavailability. The aim of the study was to develop a well-tolerated cyclodextrin (CD)-DEL complex with enhanced bioavailability and to investigate the mechanisms behind its antinociceptive effects in a preclinical model of inflammatory pain. CD-DEL was highly soluble and stable in aqueous solution, and was nontoxic.

Tissue plasminogen activator and neuropathy open the blood-nerve barrier with upregulation of microRNA-155-5p in male rats.

The blood-nerve barrier (BNB) consisting of the perineurium and endoneurial vessels is sealed by tight junction proteins. BNB alterations are a crucial factor in the pathogenesis of peripheral neuropathies. However, barrier opening, e.

Peripheral Interaction of Resolvin D1 and E1 with Opioid Receptor Antagonists for Antinociception in Inflammatory Pain in Rats.

Antinociceptive pathways are activated in the periphery in inflammatory pain, for instance resolvins and opioid peptides. Resolvins are biosynthesized from omega-3 polyunsaturated fatty acids such as eicosapentaenoic acid and docosahexaenoic acid. Resolvin D1 (RvD1) and resolvin E1 (RvE1) initiate the resolution of inflammation and control of hypersensitivity via induction of anti-inflammatory signaling cascades.

Blood-spinal cord barrier breakdown and pericyte deficiency in peripheral neuropathy.

The blood-spinal cord barrier (BSCB) prevents leakage of molecules, such as pronociceptive mediators, into the spinal cord, but its role in the pathophysiology of neuropathic pain is not completely understood. Rats with chronic constriction injury (CCI) develop mechanical allodynia, thermal hypersensitivity, and reduced motor performance (Rota-Rod test) compared with sham-injured mice-similar to mice with spared nerve injury (SNI). The BSCB becomes permeable for small and large tracers 1 day after nerve ligation.

Inflammatory pain control by blocking oxidized phospholipid-mediated TRP channel activation.

Phospholipids occurring in cell membranes and lipoproteins are converted into oxidized phospholipids (OxPL) by oxidative stress promoting atherosclerotic plaque formation. Here, OxPL were characterized as novel targets in acute and chronic inflammatory pain. Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) and its derivatives were identified in inflamed tissue by mass spectrometry and binding assays.

A Novel Approach for the Control of Inflammatory Pain: Prostaglandin E2 Complexation by Randomly Methylated β-Cyclodextrins.

Background: Inhibitors of cyclooxygenase, which block the formation of prostaglandin (PG) E2, are the standard treatment of inflammatory pain. These drugs, however, have serious gastrointestinal, renal, and cardiovascular side effects that limit their clinical use. Cyclodextrins are neutral glucose oligomers that form a hydrophilic outer and a hydrophobic interior cavity used to carry hydrophilic substances.

Functional and structural characterization of axonal opioid receptors as targets for analgesia.

Background: Opioids are the gold standard for the treatment of acute pain despite serious side effects in the central and enteric nervous system. µ-opioid receptors (MOPs) are expressed and functional at the terminals of sensory axons, when activated by exogenous or endogenous ligands. However, the presence and function of MOP along nociceptive axons remains controversial particularly in naïve animals.

Analgesic drug delivery via recombinant tissue plasminogen activator and microRNA-183-triggered opening of the blood-nerve barrier.

The peripheral nerve contains three barriers which include the blood-nerve barrier consisting of endoneurial vessels and the perineurium as well as autotypic junctions in Schwann cells. The perineurium prevents diffusion of perineurally injected drugs that can be used for selective regional pain control. It is composed of a basal membrane and layers of perineurial cells sealed by tight junction proteins like claudin-1.

Safety, efficacy, and molecular mechanism of claudin-1-specific peptides to enhance blood-nerve-barrier permeability.

The blood-nerve barrier consists of the perineurium and endoneurial vessels. The perineurial barrier is composed of a basal membrane and a layer of perineurial cells sealed by tight junction proteins preventing e.g.

CXCL10 controls inflammatory pain via opioid peptide-containing macrophages in electroacupuncture.

Acupuncture is widely used for pain treatment in patients with osteoarthritis or low back pain, but molecular mechanisms remain largely enigmatic. In the early phase of inflammation neutrophilic chemokines direct opioid-containing neutrophils in the inflamed tissue and stimulate opioid peptide release and antinociception. In this study the molecular pathway and neuroimmune connections in complete Freund's adjuvant (CFA)-induced hind paw inflammation and electroacupuncture for peripheral pain control were analyzed.

Thoracic epidural anesthesia decreases endotoxin-induced endothelial injury.

Background: The sympathetic nervous system is considered to modulate the endotoxin-induced activation of immune cells. Here we investigate whether thoracic epidural anesthesia with its regional symapathetic blocking effect alters endotoxin-induced leukocyte-endothelium activation and interaction with subsequent endothelial injury.

Methods: Sprague Dawley rats were anesthetized, cannulated and hemodynamically monitored.

New concepts and materials for the manufacturing of MR-compatible guide wires.

This paper shows the development of a new magnetic resonance imaging (MRI)-compatible guide wire made from fiber-reinforced plastics. The basic material of the developed guide wire is manufactured using a specially developed micro-pullwinding technology, which allows the adjustment of tensile, bending, and torsional stiffness independent from each other. Additionally, the micro-pullwinding technology provides the possibility to vary the stiffness along the length of the guide wire in a continuous process.

Toll like receptor (TLR)-4 as a regulator of peripheral endogenous opioid-mediated analgesia in inflammation.

Background: Leukocytes containing opioid peptides locally control inflammatory pain. In the early phase of complete Freund's adjuvant (CFA)-induced hind paw inflammation, formyl peptides (derived e.g.

The molecular link between C-C-chemokine ligand 2-induced leukocyte recruitment and hyperalgesia.

Unlabelled: The chemokine C-C-chemokine ligand 2 (CCL2) (formerly known as MCP, macrophage chemotactic protein) is one of the important genes upregulated in different types of pain both in animals and humans. CCL2 governs the recruitment of C-C chemokine receptor 2-expressing monocytes into inflamed tissue. In contrast to neutrophilic chemokines, intraplantar injection of CCL2 in Wistar rats recruited macrophages and neutrophils and simultaneously lowered nociceptive thresholds.

The connection of monocytes and reactive oxygen species in pain.

The interplay of specific leukocyte subpopulations, resident cells and proalgesic mediators results in pain in inflammation. Proalgesic mediators like reactive oxygen species (ROS) and downstream products elicit pain by stimulation of transient receptor potential (TRP) channels. The contribution of leukocyte subpopulations however is less clear.