Inhibition of inflammatory pain by CRF at peripheral, spinal and supraspinal sites: involvement of areas coexpressing CRF receptors and opioid peptides

Title

Inhibition of inflammatory pain by CRF at peripheral, spinal and supraspinal sites: involvement of areas coexpressing CRF receptors and opioid peptides

Creator

Mousa SA; Bopaiah CP; Richter JF; Yamdeu RS; Schafer M

Publisher

Neuropsychopharmacology

Date

2007

Subject

Male; Pain Measurement; Animals; Rats; Biomarkers of Pain; Dose-Response Relationship; Drug; Receptors; Freund's Adjuvant; Wistar; Animal; Disease Models; Analgesics/administration & dosage; Drug Administration Routes; Pain Threshold/drug effects; Brain/drug effects/metabolism; Spinal Cord/drug effects/metabolism; Corticotropin-Releasing Hormone/administration & dosage; Opioid Peptides/metabolism; Corticotropin-Releasing Hormone/metabolism; Ganglia; Hormone Antagonists/administration & dosage; Inflammation/chemically induced/complications; Pain/drug therapy/etiology/pathology; Sciatic Nerve/pathology; Spinal/drug effects/metabolism

Description

There is conflicting evidence on the antinociceptive effects of corticotropin-releasing factor (CRF) along the neuraxis of pain transmission and the responsible anatomical sites of CRF's action at the level of the brain, spinal cord and periphery. In an animal model of tonic pain, that is, Freunds complete adjuvant (FCA) hindpaw inflammation, we systematically investigated CRF's ability to modulate inflammatory pain at those three levels of pain transmission by algesiometry following the intracerebroventricular, intrathecal, and intraplantar application of low, systemically inactive doses of CRF. At each level, CRF elicits potent antinociceptive effects, which are dose dependent and antagonized by local, but not systemic CRF receptor antagonist alpha-helical CRF indicating CRF receptor specificity. Consistently, we have identified by immunohistochemistry multiple brain areas, inhibitory interneurons within the dorsal horn of the spinal cord as well as immune cells within subcutaneous tissue--but not peripheral sensory neurons--that coexpress both CRF receptors and opioid peptides. In line with these anatomical findings, local administration of CRF together with the opioid receptor antagonist naloxone dose-dependently reversed CRF's antinociceptive effects at each of these three levels of pain transmission. Therefore, local application of low, systemically inactive doses of CRF at the level of the brain, spinal cord and periphery inhibits tonic inflammatory pain most likely through an activation of CRF receptors on cells that coexpress opioid peptides which results in opioid-mediated pain inhibition. Future studies have to delineate whether endogenous CRF at these three levels contributes to the body's response to cope with the stressful stimulus pain in an opioid-mediated manner.
2007

Rights

Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).

Type

Journal Article

Citation List Month

Backlog

Pages

2530-2542

Issue

12

Volume

32

Citation

Mousa SA; Bopaiah CP; Richter JF; Yamdeu RS; Schafer M, “Inhibition of inflammatory pain by CRF at peripheral, spinal and supraspinal sites: involvement of areas coexpressing CRF receptors and opioid peptides,” Pediatric Palliative Care Library, accessed May 21, 2022, https://pedpalascnetlibrary.omeka.net/items/show/14308.

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