Chronic administration of the selective P2X3, P2X2/3 receptor antagonist, A-317491, transiently attenuates cancer-induced bone pain in mice.
The purinergic P2X3 and P2X2/3 receptors are in the peripheral nervous system almost exclusively confined to afferent sensory neurons, where they are found both at peripheral and central synapses. The P2X3 receptor is implicated in both neuropathic and inflammatory pain. However, the role of the P2X3 receptor in chronic cancer-induced bone pain is less known. Here we investigated the effect of systemic acute and chronic administration of the selective P2X3, P2X2/3 receptor antagonist (5-[[[(3-Phenoxyphenyl)methyl][(1S)-1,2,3,4-tetrahydro-1-naphthalenyl]amino]carbonyl]-1,2,4-benzenetricarboxylic acid sodium salt hydrate) (A-317491) in a murine model of cancer-induced bone pain. Chronic administration of A-317491 (30 μmol/kgs.c., b.i.d.) resulted in a transient attenuation of pain related behaviours in the early stage of the bone cancer model, but had no effect in the late and more progressed stage of bone cancer. Also, acute administration of A-317491 (100 μmol/kgs.c.) had no effect in the progressed stage of the bone cancer pain model. Thus, systemically administered A-317491 did not demonstrate a robust effect in the present mouse model of cancer-induced bone pain.
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
Rikke Rie
RR
Hansen
Arafat
A
Nasser
Sarah
S
Falk
Signe B
SB
Baldvinsson
Pernille H
PH
Ohlsson
Justyna M C
JM
Bahl
Michael F
MF
Jarvis
Ming
M
Ding
Anne-Marie
AM
Heegaard
D000818:Animals; D001859:Bone Neoplasms / Q000150:complications*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D010146:Pain / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D010636:Phenols / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D011083:Polycyclic Compounds / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D058920:Purinergic P2X Receptor Antagonists / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D058476:Receptors, Purinergic P2X2 / Q000378:metabolism*; D058477:Receptors, Purinergic P2X3 / Q000378:metabolism*; D013997:Time Factors
C470346:A-317491; D010636:Phenols; D011083:Polycyclic Compounds; D058920:Purinergic P2X Receptor Antagonists; D058476:Receptors, Purinergic P2X2; D058477:Receptors, Purinergic P2X3