Does Opioid Use Cause Angiogenesis and Metastasis?

Pain Med. 2017 Jan 1;18(1):140-151. doi: 10.1093/pm/pnw132.


Objective: To provide a comprehensive overview of the potential for morphine to lead to angiogenesis and metastasis.

Background: Morphine is often the treatment of choice for severe cancer-related pain. Small studies have been emerging that indicate that opioids may influence angiogenesis and metastasis, but this has not yet been comprehensively synthesized.

Purpose: To highlight morphine's relationship with angiogenesis and metastasis in in vitro models.

Method: A review of the literature was conducted using PubMed (1966 to 2015) and Cochrane Library (1987 to 2015) electronic databases. The search, as well as consultation with experts, yielded 84 articles for initial review, 12 of which met inclusion for review. Possible theories of the underlying etiology of the metastasis and angiogenesis were recorded.

Results: All studies were assessed using the PRISMA checklist.

Conclusion: This systematic review demonstrates that morphine has a potential causal relationship with angiogenesis and metastasis. This is likely due to multiple etiologies, including immunosuppressive, pro-inflammatory, and pro-angiogenetic.

Keywords: Morphine Metastasis; Opioid Angiogenesis; Preventing Angiogenesis/Metastasis.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Analgesics, Opioid / adverse effects*
  • Humans
  • Morphine / adverse effects*
  • Neoplasm Invasiveness*
  • Neoplasms / complications
  • Neoplasms / pathology*
  • Neovascularization, Pathologic*
  • Pain / drug therapy
  • Pain / etiology


  • Analgesics, Opioid
  • Morphine