Interleukin-6 in combination with its soluble IL-6 receptor sensitises rat skin nociceptors to heat, in vivo

Interleukin-6 (IL-6) contributes to increased pain and hyperalgesia in inflamed tissue, We have investigated the effects of IL-6. alone or in combination with its soluble receptor (sIL-6R), on the sensitivity of nociceptors to noxious heat, using dermal microdialysis. Plasmapheresis membranes were inserted into the abdominal skin of adult male Wistar rats (n = 46) and perfused with modified Ringer solution. After three control samples (20 min each), the skin area above the membrane was heated to 48degreesC for 20 min. The stimulation was followed by two washout samples. The calcitonin gene-related peptide (CGRP) content of the dialysate was measured with an enzyme immunoassay. Heat stimulation provoked a significant CGRP increase in (he dialysate. Intradermal application of IL-6 (200 ng ml(-1)) did not significantly alter heat-induced CGRP release. However, a significant sensitisation of the heat-induced CGRP release was observed when sIL-6R (25 ng ml(-1)) was applied, either alone or in combination with IL-6. Neutralisation of endogenous IL-6 with a sheep anti-rat IL-6 serum did not alter heatinduced CGRP release, but abolished the sIL-6R-mediated sensitising effect. We show that IL-6 in combination with its soluble receptor can sensitise nociceptors to heat and provide evidence for the constitutive expression of the signalling molecule gp130. but not of the IL-6-membrane-bound (specific) receptor, in nociceptors. (C) 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.