LOCAL UP-REGULATION OF CORTICOTROPIN-RELEASING HORMONE AND INTERLEUKIN-1 RECEPTORS IN RATS WITH PAINFUL HINDLIMB INFLAMMATION

Opioid peptides derived from immune cells produce analgesia by activat ing opioid receptors on peripheral sensory nerves in inflammation. Cor ticotropin-releasing hormone (CRH) and interleukin-1 beta (IL-1 beta) can release these opioids. Here we show that both corticotropin-releas ing hormone and interleukin-1 beta elicit receptor-specific antinocice ption in inflamed paws of rats by an opioid-mediated mechanism. Autora diographic studies demonstrate I-125-CRH and I-125-IL-1 beta binding s ites 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. I-1 25-CRH and I-125-IL-1 beta binding sites are absent on nerves and in n on-inflamed subcutaneous tissue but their number is greatly enhanced i n inflamed paws and lymph nodes. This upregulation of binding sites fo r the opioid-releasing agents corticotropin-releasing hormone and inte rleukin-1 beta likely represents part of the body's local response to combat inflammatory pain.