To study the role of IL-6 in articular nociception, afferent nerve fibers with a receptive field in the knee joint were recorded extracellularly in healthy sodium thiopentone-anesthetized adult rats. The knee joint was mechanically stimulated by innocuous (20 mNm) or noxious (40 mNm) torque for 15 sec each. Fibers were classified as A[delta]- or as C-fibers by their conduction velocity. Initially the fibers responded on average with 7–27 action potentials to innocuous and with 82–112 action potentials to noxious test stimuli. A single intraarticular injection of 20 ng IL-6 increased the response rate of C-type fibers to noxious stimulation twofold at a slow time course. This effect was enhanced up to threefold when 100 ng IL-6 were applied. The effect lasted more than 1 hour. The enhancing effect of 100 ng IL-6 was blocked when IL-6 was applied together with the soluble cytokine receptor sgp130. Intraarticular injection of 100 ng sgp130 alone had no effects. Interestingly, IL-6 did not enhance the response rates of A[delta]-type nerve fibers to mechanical stimuli. Our data indicate that IL-6 enhances mechanosensitivity of articular C-fibers but not of articular A[delta]-fibers. Supported by IZKF Jena (B307–04004)