Y1 receptor knockout increases nociception and prevents the anti-allodynic actions of NPY.
OBJECTIVE
Recent pharmacologic studies in our laboratory have suggested that the spinal neuropeptide Y (NPY) Y1 receptor contributes to pain inhibition and to the analgesic effects of NPY. To rule out off-target effects, the present study used Y1-receptor-deficient (-/-) mice to further explore the contribution of Y1 receptors to pain modulation.


RESULTS
Y1(-/-) mice exhibited reduced latency in the hotplate test of acute pain and a longer-lasting heat allodynia in the complete Freund's adjuvant (CFA) model of inflammatory pain. Y1 deletion did not change CFA-induced inflammation. Upon targeting the spinal NPY systems with intrathecal drug delivery, NPY reduced tactile and heat allodynia in the CFA model and the partial sciatic nerve ligation model of neuropathic pain. Importantly, we show for the first time that NPY does not exert these anti-allodynic effects in Y1(-/-) mice. Furthermore, in nerve-injured CD1 mice, concomitant injection of the potent Y1 antagonist BIBO3304 prevented the anti-allodynic actions of NPY. Neither NPY nor BIBO3304 altered performance on the Rotorod test, arguing against an indirect effect of motor function.


CONCLUSIONS
The Y1 receptor contributes to pain inhibition and to the analgesic effects of NPY.
Kuphal
K E
KE
Division of Pharmacology, University of Missouri-Kansas City, Kansas City, Missouri, USA.
Solway
B
B
Pedrazzini
T
T
Taylor
B K
BK
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D006358:Hot Temperature / Q000009:adverse effects; D006930:Hyperalgesia / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009478:Neuropeptide Y / Q000235:genetics / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods / Q000706:statistics & numerical data; D017476:Receptors, Neuropeptide Y / Q000502:physiology*; D020426:Sciatic Neuropathy / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D001120:Arginine; C117416:BIBO 3304