IMMUNE CELL-DERIVED BETA-ENDORPHIN - PRODUCTION, RELEASE, AND CONTROLOF INFLAMMATORY PAIN IN RATS

Localized inflammation of a rat's hindpaw elicits an accumulation of b eta-endorphin-(END) containing immune cells, We investigated the produ ction, release, and antinociceptive effects of lymphocyte-derived END in relation to cell trafficking, In normal animals, END and proopiomel anocortin mRNA were less abundant in circulating lymphocytes than in t hose residing in lymph nodes (LN), suggesting that a finite cell popul ation produces END and homes to LN, Inflammation increased proopiomela nocortin mRNA in cells from noninflamed and inflamed LN, However, END content was increased only in inflamed paw tissue and noninflamed LN-i mmune cells, Accordingly, corticotropin-releasing factor and IL-1 beta released significantly more END from noninflamed than from inflamed L N-immune cells, This secretion was receptor specific, calcium dependen t, and mimicked by potassium, consistent with vesicular release, Final ly, both agents, injected into the inflamed paw, induced analgesia whi ch was blocked by the co-administration of antiserum against END, Toge ther, these findings suggest that END-producing lymphocytes home to in flamed tissue where they secrete END to reduce pain, afterwards they m igrate to the regional LN, depleted of the peptide, Consistent with th is notion, immunofluorescence studies of cell suspensions revealed tha t END is contained predominantly within memory-type T cells, Thus, the immune system is important for the control of inflammatory pain, This has implications for the understanding of pain in immunosuppressed co nditions like cancer or AIDS.