Impaired pain sensation in mice lacking prokineticin 2.
Prokineticins (PKs), consisting of PK1 and PK2, are a pair of newly identified regulatory peptides. Two closely related G-protein coupled receptors, PKR1 and PKR2, mediate the signaling of PKs. PKs/PKRs participate in the regulation of diverse biological processes, ranging from development to adult physiology. A number of studies have indicated the involvement of PKs/PKRs in nociception. Here we show that PK2 is a sensitizer for nociception. Intraplantar injection of recombinant PK2 resulted in a strong and localized hyperalgesia with reduced thresholds to nociceptive stimuli. PK2 mobilizes calcium in dissociated dorsal root ganglion (DRG) neurons. Mice lacking the PK2 gene displayed strong reduction in nociception induced by thermal and chemical stimuli, including capsaicin. However, PK2 mutant mice showed no difference in inflammatory response to capsaicin. As the majority of PK2-responsive DRG neurons also expressed transient receptor potential vanilloid (TRPV1) and exhibited sensitivity to capsaicin, TRPV1 is likely a significant downstream molecule of PK2 signaling. Taken together, these results reveal that PK2 sensitize nociception without affecting inflammation.
Hu
Wang-Ping
WP
Department of Pharmacology, University of California, Irvine, CA 92697, USA. wangpinh@uci.edu
Zhang
Chengkang
C
Li
Jia-Da
JD
Luo
Z David
ZD
Amadesi
Silvia
S
Bunnett
Nigel
N
Zhou
Qun-Yong
QY
D000818:Animals; D001522:Behavior, Animal; D002211:Capsaicin; D005727:Ganglia, Spinal / Q000166:cytology; D005768:Gastrointestinal Hormones / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D006987:Hypesthesia / Q000235:genetics* / Q000503:physiopathology*; D017403:In Situ Hybridization / Q000379:methods; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D010146:Pain / Q000235:genetics / Q000503:physiopathology; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D010812:Physical Stimulation / Q000379:methods; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D013268:Stimulation, Chemical; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism
D005768:Gastrointestinal Hormones; D009479:Neuropeptides; C486586:Prok2 protein, mouse; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D002211:Capsaicin