Abstract
Purpose
Bone metastasis is one of the major causes of cancer-related pain, and not all bone cancer pain can be effectively treated. Recently, a mouse model of bone cancer pain was introduced. To test the analgesic effects of nonsteroidal antiinflammatory drugs on bone cancer pain, the authors examined the effects of oral administration of a cyclooxygenase-1 (COX-1) selective inhibitor (SC560), a COX-2 selective inhibitor (celecoxib), and a nonselective COX inhibitor (indomethacin) on bone cancer pain and compared these effects to the effect of orally administered acetaminophen and morphine.
Methods
An animal model of bone cancer pain was induced by injecting osteolytic murine sarcoma cells in the mouse femur. Drugs were administered orally 2 weeks after tumor-cell implantation, and the level of bone cancer pain was assessed 30, 60, 90, 120, and 180 min after drug administration.
Results
Oral administration of acetaminophen, indomethacin, and morphine, but not of SC560 or celecoxib, produced an analgesic effect on bone cancer pain. Co-administration of a subanalgesic does of morphine with acetaminophen enhanced the analgesic effect of acetaminophen.
Conclusion
These data suggest that bone cancer pain is effectively treated by oral administration of indomethacin, acetaminophen, and morphine and that the co-administration of acetaminophen and an opioid provides a beneficial effect when treating of bone cancer pain.
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References
RG Twycross S Fairfield (1982) ArticleTitlePain in far-advanced cancer Pain 14 303–310
FJ Brescia D Adler G Gray MA Ryan J Cimino R Mamtani (1990) ArticleTitleHospitalized advanced caner patients: a profile J Pain Symptom Manage 5 221–227
S Mercadante (1997) ArticleTitleMalignant bone pain: pathophysiology and treatment Pain 69 1–18
InstitutionalAuthorNameWorld Health Organization (1984) Cancer pain relief WHO Geneva
SH Ferreira S Moncada JR Vane (1973) ArticleTitleProstaglandins and the mechanism of analgesia produced by aspirin-like drugs Br J Pharmacol 49 86–97
JR Vane YS Bakhle RM Blotting (1998) ArticleTitleCyclooxygease 1 and 2 Annu Rev Pharmacol Toxicol 38 97–120
T Yamamoto N Nozaki-Taguchi (1996) ArticleTitleAnalysis of the effect of cyclooxygenase (COX)-1 and COX-2 in spinal nociceptive transmission using indomethacin, a non-selective COX inhibitor, and NS-398, a COX-2 selective inhibitor Brain Res 739 104–110
NV Chandrasekharan H Dai KL Roos NK Evanson J Tomsik TS Elton DL Simmons (2002) ArticleTitleCOX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression Proc Natl Acad Sci USA 99 13926–13931
JA Snipes B Kis GS Shelness JA Hewett DW Busija (2005) ArticleTitleCloning and characterization of cyclooxygenase-1b (putative COX-3) in rat J Pharmacol Exp Ther 313 668–676
DL Simmons RM Botting PM Robertson ML Madsen JR Vane (1999) ArticleTitleInduction of an acetaminophen-sensitive cyclooxygenase with reduced sensitivity to nonsteroidal antiinflammatory drugs Proc Natl Acad Sci USA 96 3275–3280
MJ Schwei P Honore SD Rogers JL Salak-Johnson MP Finke ML Ramnaraine DR Clohisy PW Mantyh (1999) ArticleTitleNeurochemical and cellular reorganization of the spinal cord in a murine model of bone cancer pain J Neurosci 19 10886–10897
DR Clohisy CM Ogilvie ML Ramnaraine (1995) ArticleTitleTumor osteolysis in osteopetrotic mice J Orthop Res 13 892–897
DR Clohisy CM Ogilvie RJ Carpenter ML Ramnaraine (1996) ArticleTitleLocalized, tumor-associated osteolysis involves the recruitment and activation of osteoclasts J Orthop Res 14 2–6
JH Zar (1984) Bio-statistical analysis Prentice-Hall Englewood Cliffs, NJ
B Kis JA Snipes SA Simandle DW Busija (2005) ArticleTitleAcetaminophen-sensitive prostaglandin production in rat cerebral endothelial cells Am J Physiol Regul Integr Comp Physiol 288 R897–R902
CJ Smith Y Zhang CM Koboldt J Muhammad BS Zweifel A Shaffer JJ Talley JL Masferrer K Seibert PC Isakson (1998) ArticleTitlePharmacological analysis of cyclooxygenase-1 in inflammation Proc Natl Acad Sci USA 95 13313–13318
T Yamamoto N Nozaki-Taguchi (2002) ArticleTitleThe role of cyclooxigenase-1 and -2 in the rat formalin test Anesth Analg 94 962–967
MAC Sabino JR Ghilardi JLM Jongen CP Keyser NM Luger DB Mach CM Peters SD Rogers MJ Schwei C de Felipe PW Mantyh (2002) ArticleTitleSimultaneous reduction in cancer pain, bone destruction, and tumor growth by selective inhibition of cyclooxygenase-2 Cancer Res 62 7343–7349
K Walker SJ Medhurst BL Kidd M Glatt M Bowes S Patel K McNair A Kesingland J Green O Chan AJ Fox LA Urban (2002) ArticleTitleDisease modifying and anti-nociceptive effects of the bisphosphonate, zoledronic acid in a model of bone cancer pain Pain 100 219–229
SJ Medhurst K Walker M Bowes BL Kidd M Glatt M Muller M Hattenberger J Vaxelaire T O’reilly G Wotherspoon J Winter J Green L Urban (2002) ArticleTitleA rat model of bone cancer pain Pain 96 129–140
AI Basbaum HL Fields (1984) ArticleTitleEndogenous pain control systems: brain stem, spinal cord and endorphin circuitry Annu Rev Neurosci 7 309–338
CW Vaughan SL Ingram MA Connor MJ Christie (1997) ArticleTitleHow opioids inhibit GABA-mediated neurotransmission Nature 390 611–614
CW Vaughan (1998) ArticleTitleEnhancement of opioid inhibition of GABAergic synaptic transmission by cyclo-oxygenase inhibitors in rat periaqueductal grey neurons Br J Pharmacol 123 1479–1481
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Saito, O., Aoe, T. & Yamamoto, T. Analgesic effects of nonsteroidal antiinflammatory drugs, acetaminophen, and morphine in a mouse model of bone cancer pain. J Anesth 19, 218–224 (2005). https://doi.org/10.1007/s00540-005-0323-3
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DOI: https://doi.org/10.1007/s00540-005-0323-3