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

Pain. 2013 Feb;154(2):294-305. doi: 10.1016/j.pain.2012.10.022. Epub 2012 Nov 5.


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, 0.08mL, 40μg Mycobacterium tuberculosis) into one hind paw of the rat. Paw withdrawal latency (PWL) was tested before (-48h) and 2 and 24h after CFA injection to assess hyperalgesia. IL-17 antibody (0.2-2μg/rat) was given intrathecally (i.t.) 24h before CFA to block the action of basal IL-17 and 2h before each of 2 PWL tests to block CFA-induced IL-17. I.t. recombinant IL-17 (10-400ng 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 2μg/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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Freund's Adjuvant
  • Hot Temperature
  • Hyperalgesia / chemically induced
  • Hyperalgesia / metabolism*
  • Inflammation / chemically induced
  • Inflammation / metabolism*
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism*
  • Male
  • Neurons / drug effects
  • Neurons / metabolism
  • Pain Measurement
  • Pain Threshold / drug effects
  • Phosphorylation / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Interleukin-17 / genetics
  • Receptors, Interleukin-17 / metabolism*
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism


  • Antibodies
  • Interleukin-17
  • NR1 NMDA receptor
  • Receptors, Interleukin-17
  • Receptors, N-Methyl-D-Aspartate
  • Freund's Adjuvant