Spinal interleukin-17 promotes thermal hyperalgesia and NMDA NR1 phosphorylation in an inflammatory pain rat model

It is known that interleukin-17 (IL-17) is associated with autoimmune disorders and that peripheral IL-17 plays a role in arthritis and neuropathic pain. The present study investigated the possibility of spinal cell expression of IL-17 during inflammatory pain and possible IL-17 involvement in such pain. Hyperalgesia was induced by injecting complete Freund adjuvant (CFA, 0.08 mL, 40 mu g Mycobacterium tuberculosis) into one hind paw of the rat. Paw withdrawal latency (PWL) was tested before (-48 h) and 2 and 24 h after CFA injection to assess hyperalgesia. IL-17 antibody (0.2-2 mu g/rat) was given intrathecally (i.t.) 24 h before CFA to block the action of basal IL-17 and 2 h before each of 2 PWL tests to block CFA-induced IL-17. I.t. recombinant IL-17 (10-400 ng per rat) was administered to naive rats to determine its effects on PWL and phosphorylated NR1 (p-NR1). p-NR1 modulates N-methyl-D-aspartate receptor (NMDAR) activity to facilitate pain. Spinal cords were removed for IL-17 immunostaining, double immunostaining of IL-17/cell markers and IL-17 receptor A (IL-17RA)/NR1, for Western blot testing of IL-17, p-NR1, IL-17RA, and GFAP, for in situ IL-17RA hybridization, and for real time polymerase chain reaction of IL-17RA. The data reveal that IL-17 is up-regulated in activated and nonactivated astrocytes; that IL-17RA is localized in NR1-immunoreactive neurons and up-regulated; and that IL-17 antibody at 2 mu g/rat significantly increased PWL (P < .05) and decreased p-NR1 and IL-17RA compared to control in CFA- and IL-17-injected rats. The results suggest that spinal IL-17 is produced by astrocytes and enhances p-NR1 to facilitate pain. (c) 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.