Anti-hyperalgesic activity of the cox-2 inhibitor lumiracoxib in a model of bone cancer pain in the rat.
Chronic pain resulting from metastatic bone cancer remains poorly understood and resistant to treatment. Here we have examined the effect of the novel COX-2 enzyme inhibitor lumiracoxib in a model of bone cancer pain in the rat. Lumiracoxib was administered orally twice daily from day 10 to day 20 after injection of MRMT-1 tumour cells into one tibia. Mechanical hyperalgesia, measured as the reduction in weight-bearing of the ipsilateral limb, and the development of static and dynamic allodynia were significantly inhibited by repeated lumaricoxib administration. A similar reduction in hyperalgesia and allodynia was noted after twice daily administration of another COX-2 inhibitor, valdecoxib, whilst a single acute administration of either drug on day 20, produced no anti-nociceptive activity. Bone mineral density measurements, radiological scores and histological analysis showed that chronic lumaricoxib treatment also significantly attenuated bone destruction induced by tumour cell injection. These data indicate that lumiracoxib and other COX-2 inhibitors have potential therapeutic benefit in the treatment of bone cancer pain.
Fox
Alyson
A
Novartis Institute for Medical Sciences, 5 Gower Place, London WC1E 6BS, UK. alyson.fox@pharma.novartis.com
Medhurst
Stephen
S
Courade
Jean-Philippe
JP
Glatt
Marcus
M
Dawson
Janet
J
Urban
Laszlo
L
Bevan
Stuart
S
Gonzalez
Isabel
I
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D015519:Bone Density; D001859:Bone Neoplasms / Q000150:complications* / Q000473:pathology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004008:Diclofenac / Q000031:analogs & derivatives; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005620:Freund's Adjuvant; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007555:Isoxazoles / Q000627:therapeutic use; D009930:Organic Chemicals / Q000627:therapeutic use*; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement; D011451:Prostaglandin-Endoperoxide Synthases; D011871:Radiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000627:therapeutic use; D013997:Time Factors; D014407:Tumor Cells, Cultured; D000096926:Benzenesulfonamides
D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004008:Diclofenac; D005620:Freund's Adjuvant; D007527:Isoenzymes; D007555:Isoxazoles; D009930:Organic Chemicals; D011451:Prostaglandin-Endoperoxide Synthases; D013449:Sulfonamides; C406224:valdecoxib; D000096926:Benzenesulfonamides; C473384:lumiracoxib