Morphine analgesia suppresses tumor growth and metastasis in a mouse model of cancer pain produced by orthotopic tumor inoculation

Eur J Pharmacol. 2002 Apr 26;441(3):185-91. doi: 10.1016/s0014-2999(02)01450-4.


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.

MeSH terms

  • Analgesics, Opioid / therapeutic use*
  • Animals
  • Disease Models, Animal*
  • Dose-Response Relationship, Drug
  • Male
  • Melanoma, Experimental / complications
  • Melanoma, Experimental / drug therapy*
  • Mice
  • Mice, Inbred C57BL
  • Morphine / therapeutic use*
  • Neoplasm Metastasis / drug therapy*
  • Neoplasms / complications
  • Neoplasms / drug therapy
  • Pain / drug therapy*
  • Pain / etiology
  • Xenograft Model Antitumor Assays / methods


  • Analgesics, Opioid
  • Morphine