Morphine analgesia suppresses tumor growth and metastasis in a mouse model of cancer pain produced by orthotopic tumor inoculation.
The present study was conducted to clarify whether relief from cancer pain by morphine would suppress tumor growth and metastasis. When given orthotopic inoculation of B16-BL6 melanoma cells into the hind paw, C57BL/6 mice showed moderate and marked hyperalgesia on days 7-10 and from day 14 post-inoculation, respectively. The volume of inoculated hind paw was increased exponentially as a function of time from day 8 post-inoculation, a phenomena being due to melanoma growth. Lung metastasis was apparent after day 12 post-inoculation. On day 16 post-inoculation, the hyperalgesia was completely inhibited by subcutaneous injection of morphine hydrochloride (5 and 10 mg/kg). The tumor growth and lung metastasis were markedly inhibited by repeated administration of morphine (5 and 10 mg/kg daily for 6 days) and also by the neurectomy of sciatic nerve innervating the inoculated region. The results suggest that relief from cancer pain by morphine inhibits tumor growth and metastasis.
Sasamura
Takashi
T
Department of Applied Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
Nakamura
Shigenobu
S
Iida
Yuko
Y
Fujii
Hideki
H
Murata
Jun
J
Saiki
Ikuo
I
Nojima
Hiroshi
H
Kuraishi
Yasushi
Y
D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D008546:Melanoma, Experimental / Q000150:complications / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000627:therapeutic use*; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D000701:Analgesics, Opioid; D009020:Morphine