Local upregulation of corticotropin-releasing hormone and interleukin-1 receptors in rats with painful hindlimb inflammation.
Opioid peptides derived from immune cells produce analgesia by activating opioid receptors on peripheral sensory nerves in inflammation. Corticotropin-releasing hormone (CRH) and interleukin-1 beta (IL-1 beta) can release these opioids. Here we show that both corticotropin-releasing hormone and interleukin-1 beta elicit receptor-specific antinociception in inflamed paws of rats by an opioid-mediated mechanism. Autoradiographic studies demonstrate 125I-CRH and 125I-IL-1 beta binding sites on immune cells in lymph nodes and inflamed paws. This binding is of high affinity and displaceable by the respective unlabeled agonist and antagonist ligands but not by opioid or adrenergic compounds. 125I-CRH and 125I-IL-1 beta binding sites are absent on nerves and in non-inflamed subcutaneous tissue but their number is greatly enhanced in inflamed paws and lymph nodes. This upregulation of binding sites for the opioid-releasing agents corticotropin-releasing hormone and interleukin-1 beta likely represents part of the body's local response to combat inflammatory pain.
Preclinical Pharmacology Laboratory, National Institute on Drug Abuse, NIH, Baltimore, MD 21224, USA.
S A
SA
Mousa
M
M
Schäfer
W M
WM
Mitchell
A H
AH
Hassan
C
C
Stein
D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D006614:Hindlimb / Q000187:drug effects; D007249:Inflammation / Q000503:physiopathology*; D007375:Interleukin-1 / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism*; D008297:Male; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D015854:Up-Regulation
D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D003346:Corticotropin-Releasing Hormone