Electrophysiological evidence that the vasoactive intestinal peptide receptor antagonist VIP6-28 reduces nociception in an animal model of osteoarthritis.
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.
Schuelert
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Department of Physiology & Biophysics, University of Calgary, Calgary, Alberta, Canada.
McDougall
J J
JJ
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*
D010446:Peptide Fragments; D018005:Receptors, Vasoactive Intestinal Peptide; C113198:vasoactive intestinal peptide (6-28); D014660:Vasoactive Intestinal Peptide