Superior control of inflammatory pain by corticotropin-releasing factor receptor 1 via opioid peptides in distinct pain-relevant brain areas.

Background: Under inflammatory conditions, the activation of corticotropin-releasing factor (CRF) receptor has been shown to inhibit pain through opioid peptide release from immune cells or neurons. CRF's effects on human and animal pain modulation depend, however, on the distribution of its receptor subtypes 1 and 2 (CRF-R1 and CRF-R2) along the neuraxis of pain transmission. The objective of this study is to investigate the respective role of each CRF receptor subtype on centrally administered CRF-induced antinociception during inflammatory pain.

Functional and Anatomical Characterization of Corticotropin-Releasing Factor Receptor Subtypes of the Rat Spinal Cord Involved in Somatic Pain Relief.

Corticotropin-releasing factor (CRF) orchestrates our body's response to stressful stimuli. Pain is often stressful and counterbalanced by activation of CRF receptors along the nociceptive pathway, although the involvement of the CRF receptor subtypes 1 and/or 2 (CRF-R1 and CRF-R2, respectively) in CRF-induced analgesia remains controversial. Thus, the aim of the present study was to examine CRF-R1 and CRF-R2 expression within the spinal cord of rats with Freund's complete adjuvant-induced unilateral inflammation of the hind paw using reverse transcriptase polymerase chain reaction, Western blot, radioligand binding, and immunofluorescence confocal analysis.

Prostanoid Receptor Subtypes and Its Endogenous Ligands with Processing Enzymes within Various Types of Inflammatory Joint Diseases.

A complex inflammatory process mediated by proinflammatory cytokines and prostaglandins commonly occurs in the synovial tissue of patients with joint trauma (JT), osteoarthritis (OA), and rheumatoid arthritis (RA). This study systematically investigated the distinct expression profile of prostaglandin E2 (PGE2), its processing enzymes (COX-2), and microsomal PGES-1 (mPGES-1) as well as the corresponding prostanoid receptor subtypes (EP1-4) in representative samples of synovial tissue from these patients (JT, OA, and RA). Quantitative TaqMan®-PCR and double immunofluorescence confocal microscopy of synovial tissue determined the abundance and exact immune cell types expressing these target molecules.

Accessibility of axonal G protein coupled mu-opioid receptors requires conceptual changes of axonal membrane targeting for pain modulation.

The mechanisms of axonal trafficking and membrane targeting are well established for sodium channels, which are the principle targets for perineurally applied local anaesthetics. However, they have not been thoroughly investigated for G protein coupled receptors such as mu-opioid receptors (MOR). Focusing on these axonal mechanisms, we found that axonal MOR functionality is quite distinct in two different pain states, i.

Comparative Expression Analyses of Pro- versus Anti-Inflammatory Mediators within Synovium of Patients with Joint Trauma, Osteoarthritis, and Rheumatoid Arthritis.

Synovial injury and healing are complex processes including catabolic effects by proinflammatory cytokines and anabolic processes by anti-inflammatory mediators. Here we examined the expression of pro- versus anti-inflammatory mediators in synovium of patients with diagnostic arthroscopy (control), joint trauma (JT), osteoarthritis (OA), and rheumatoid arthritis (RA). Synovial samples from these patients were subjected to RT-PCR and double immunofluorescence confocal microscopy of pro- and anti-inflammatory mediators as well as immune cell markers.

Acute mechanical sensitization of peripheral nociceptors by aldosterone through non-genomic activation of membrane bound mineralocorticoid receptors in naive rats.

Recently, there is increasing interest in the role of peripheral mineralocorticoid receptors (MR) to modulate pain, but their localization in neurons and glia of the periphery and their distinct involvement in pain control remains elusive. In naive Wistar rats our double immunofluorescence confocal microscopy of the spinal cord, dorsal root ganglia, sciatic nerve and innervated skin revealed that MR predominantly colocalized with calcitonin-gene-related peptide (CGRP)- and trkA-immunoreactive (IR) nociceptive neurons and only marginally with myelinated trkB-IR mechanoreceptive and trkC-IR proprioreceptive neurons underscoring a pivotal role for MR in the modulation of pain. MR could not be detected in Schwann cells, satellite cells, and astrocytes and only scarcely in spinal microglia cells excluding a relevant functional role of glia-derived MR at least in naïve rats.

Protein kinase C-mediated mu-opioid receptor phosphorylation and desensitization in rats, and its prevention during early diabetes.

Painful diabetic neuropathy is associated with impaired opioid analgesia; however, the precise mechanism in sensory neurons remains unclear. This study aimed to identify putative mechanisms involved in modified opioid responsiveness during early streptozotocin-induced diabetes in rats. In this study, we demonstrate that in diabetic animals, impaired peripheral opioid analgesia is associated with a reduction in functional mu-opioid receptor (MOR) G protein coupling.