Interleukin 1 beta and corticotropin-releasing factor inhibit pain by releasing opioids from immune cells in inflamed tissue

Title

Interleukin 1 beta and corticotropin-releasing factor inhibit pain by releasing opioids from immune cells in inflamed tissue

Creator

Schafer M; Carter L; Stein C

Publisher

Proceedings Of The National Academy Of Sciences Of The United States Of America

Date

1994

Subject

Humans; Male; Analysis of Variance; Animals; Regression Analysis; Rats; Biomarkers of Pain; Injections; Dose-Response Relationship; Drug; Naloxone/pharmacology; Enkephalin; Inflammation/immunology/physiopathology; Wistar; Antibodies/pharmacology; beta-Endorphin/immunology/physiology; Corticotropin-Releasing Hormone/administration & dosage/pharmacology/therapeutic use; Cyclosporine/pharmacology; Dynorphins/immunology/physiology; Endorphins/immunology/physiology/secretion; Interleukin-1/administration & dosage/pharmacology/therapeutic use; Leucine/analogs & derivatives/pharmacology; Methionine/immunology/physiology; Pain/immunology/physiopathology/prevention & control; Recombinant Proteins/pharmacology/therapeutic use; Somatostatin/analogs & derivatives/pharmacology

Description

Local analgesic effects of exogenous opioid agonists are particularly prominent in painful inflammatory conditions and are mediated by opioid receptors on peripheral sensory nerves. The endogenous ligands of these receptors, opioid peptides, have been demonstrated in resident immune cells within inflamed tissue of animals and humans. Here we examine in vivo and in vitro whether interleukin 1 beta (IL-1) or corticotropin-releasing factor (CRF) is capable of releasing these endogenous opioids and inhibiting pain. When injected into inflamed rat paws (but not intravenously), IL-1 and CRF produce antinociception, which is reversible by IL-1 receptor antagonist and alpha-helical CRF, respectively, and by the immunosuppressant cyclosporine A. In vivo administration of antibodies against opioid peptides indicates that the effects of IL-1 and CRF are mediated by beta-endorphin and, in addition, by dynorphin A and [Met]enkephalin, respectively. Correspondingly, IL-1 effects are inhibited by mu-, delta-, and kappa-opioid antagonists, whereas CRF effects are attenuated by all except a kappa-antagonist. Finally, IL-1 and CRF produce acute release of immunoreactive beta-endorphin in cell suspensions freshly prepared from inflamed lymph nodes. This effect is reversible by IL-1 receptor antagonist and alpha-helical CRF, respectively. These findings suggest that IL-1 and CRF activate their receptors on immune cells to release opioids that subsequently occupy multiple opioid receptors on sensory nerves and result in antinociception. beta-Endorphin, mu- and delta-opioid receptors play a major role, but IL-1 and CRF appear to differentially release additional opioid peptides.
1994

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

4219-4223

Issue

10

Volume

91

Citation

Schafer M; Carter L; Stein C, “Interleukin 1 beta and corticotropin-releasing factor inhibit pain by releasing opioids from immune cells in inflamed tissue,” Pediatric Palliative Care Library, accessed May 22, 2022, https://pedpalascnetlibrary.omeka.net/items/show/12096.

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