title: Spinal interleukin-6 is an amplifier of arthritic pain in the rat.
abstract: OBJECTIVE
  Significant joint pain is usually widespread beyond the affected joint, which results from the sensitization of nociceptive neurons in the central nervous system (central sensitization). This study was undertaken to explore whether the proinflammatory cytokine interleukin-6 (IL-6) in the joint induces central sensitization, whether joint inflammation causes the release of IL-6 from the spinal cord, and whether spinal IL-6 contributes to central sensitization.
  
  
  METHODS
  In anesthetized rats, electrophysiologic recordings of spinal cord neurons with sensory input from the knee joint were made. Neuronal responses to mechanical stimulation of the rat knee and leg were monitored. IL-6 and soluble IL-6 receptor (sIL-6R) were applied to the knee joint or the spinal cord. Spinal release of IL-6 was measured by enzyme-linked immunosorbent assay. Soluble gp130, which neutralizes IL-6/sIL-6R, was spinally applied during the development of joint inflammation or during established inflammation.
  
  
  RESULTS
  A single injection of IL-6/sIL-6R into the rat knee joint as well as application of IL-6/sIL-6R to the rat spinal cord significantly increased the responses of spinal neurons to mechanical stimulation of the knee and ankle joint, i.e., induced central sensitization. Application of soluble gp130 to the rat spinal cord attenuated this effect of IL-6. The development of knee inflammation in the rat caused spinal release of IL-6. Spinal application of soluble gp130 attenuated the development of inflammation-evoked central sensitization but did not reverse it.
  
  
  CONCLUSIONS
  Our findings indicate that the generation of joint pain in the rat involves not only IL-6 in the joint but also IL-6 released from the spinal cord. Spinal IL-6 contributes to central sensitization and thus promotes the widespread hyperalgesia observed in the course of joint disease.
authors.affiliation: Institute of Physiology, Jena University Hospital, and Friedrich Schiller University Jena, Jena, Germany.
authors.forename: Enrique
authors.initials: E
authors.lastname: Vazquez
authors.forename: Jan
authors.initials: J
authors.lastname: Kahlenbach
authors.forename: Gisela
authors.initials: G
authors.lastname: Segond von Banchet
authors.forename: Christian
authors.initials: C
authors.lastname: König
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Schaible
authors.forename: Andrea
authors.initials: A
authors.lastname: Ebersberger
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001169:Arthritis, Experimental; D006930:Hyperalgesia / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology*; D007719:Knee Joint / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism
chemical_list: D015850:Interleukin-6