Methionine-enkephalin-and Dynorphin A-release from immune cells and control of inflammatory pain

Title

Methionine-enkephalin-and Dynorphin A-release from immune cells and control of inflammatory pain

Creator

Cabot PJ; Carter L; Schafer M; Stein C

Publisher

Pain

Date

2001

Subject

Humans; Male; Animals; Rats; Biomarkers of Pain; Dose-Response Relationship; Drug; Enkephalin; Biomarkers Reference List; Wistar; Antibodies/pharmacology; Corticotropin-Releasing Hormone/antagonists & inhibitors/pharmacology/therapeutic use; Dynorphins/immunology/secretion; Inflammation/drug therapy/immunology/metabolism; Interleukin-2/pharmacology; Lymphocytes/drug effects/immunology/secretion; Methionine/immunology/metabolism; Pain/drug therapy/immunology/metabolism

Description

We have previously shown that beta-endorphin (END) is contained and released from memory-type T-cells within inflamed tissue and that it is capable to control pain (J Clin Invest 100(1) (1997) 142). Methionine-enkephalin (MET) and Dynorphin-A (DYN) are endogenous opioids with preference for delta- and kappa-opioid receptors, respectively. Both MET and DYN are produced and contained within immune cells. The goal of this study was to determine the release characteristics of MET and DYN in a rat model of localized hindpaw inflammation and to examine the antinociceptive role of MET and DYN in a Freund's adjuvant induced model of inflammatory pain. We found that corticotropin-releasing factor (CRF) can stimulate the release of both MET and DYN from lymphocytes. This release is dose-dependent and reversible by the selective CRF antagonist alpha-helical-CRF. Furthermore, CRF (1.5 ng) produces analgesia when injected into the inflamed paw, which is reversible by direct co-administration of antibodies to MET. Lymphocyte content of MET was 7.0+/-1.4 ng/million cells, whilst DYN content was ~30-fold lower. Both END and DYN, but not MET, were released by IL-1. Consistently, IL-1 produced peripheral analgesic effects which were not reversed by antibodies to MET. These results indicate that both MET and DYN play a role in peripheral analgesia but have different characteristics of release. These studies further support a role of the immune system in the control of inflammatory pain. This may be particularly important in patients suffering from compromised immune systems as with cancer and AIDS.
2001

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

207-212

Issue

3

Volume

93

Citation

Cabot PJ; Carter L; Schafer M; Stein C, “Methionine-enkephalin-and Dynorphin A-release from immune cells and control of inflammatory pain,” Pediatric Palliative Care Library, accessed September 16, 2021, https://pedpalascnetlibrary.omeka.net/items/show/12230.

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