title: Electrophysiological evidence that the vasoactive intestinal peptide receptor antagonist VIP6-28 reduces nociception in an animal model of osteoarthritis.
abstract: OBJECTIVE
  The present study examined whether local administration of the neuropeptide vasoactive intestinal polypeptide (VIP) could modulate joint nociception in normal rat knee joints and if the VIP antagonist VIP(6-28) could ameliorate joint mechanosensitivity in an animal model of osteoarthritis (OA).
  
  
  METHODS
  OA was induced in male Wistar rats by intra-articular injection of 3mg sodium monoiodo-acetate with a recovery period of 14 days. Electrophysiological recordings were made from knee joint primary afferents in response to normal rotation and noxious hyper-rotation of the joint both before and following close intra-arterial injection of different doses of VIP and VIP(6-28).
  
  
  RESULTS
  Local application of VIP to normal knees caused afferent firing rate to be significantly enhanced during normal rotation (up to 180% P<0.01; n=17) and during hyper-rotation (up to 37% P<0.01; n=17) of the knee. VIP-induced sensitization was blocked by pre-administration of the VIP receptor antagonist VIP(6-28). In the OA group, application of VIP(6-28) caused afferent firing rate to be significantly reduced during normal rotation (up to 45% P<0.05; n=17) and during hyper-rotation (up to 34% P<0.01; n=15) of the knee joint.
  
  
  CONCLUSIONS
  These findings indicate that VIP is involved in peripheral sensitization of knee joint afferents especially in response to normal joint movements. OA-induced sensitization of knee joint afferents was inhibited by local administration of VIP(6-28), indicating that VIP is released into OA knee joints, potentially contributing to joint pain. As such, VIP(6-28) may prove to be a beneficial agent for the treatment of arthritis pain.
authors.affiliation: Department of Physiology & Biophysics, University of Calgary, Calgary, Alberta, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Schuelert
authors.forename: J J
authors.initials: JJ
authors.lastname: McDougall
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology / Q000379:methods; D006614:Hindlimb; D007269:Injections, Intra-Arterial; D007596:Joints / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D009068:Movement / Q000502:physiology; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D010003:Osteoarthritis / Q000503:physiopathology*; D010146:Pain / Q000188:drug therapy*; D010446:Peptide Fragments / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D018005:Receptors, Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors*; D012399:Rotation; D014660:Vasoactive Intestinal Peptide / Q000008:administration & dosage*
chemical_list: D010446:Peptide Fragments; D018005:Receptors, Vasoactive Intestinal Peptide; C113198:vasoactive intestinal peptide (6-28); D014660:Vasoactive Intestinal Peptide