Chronic Cancer Pain: Opioids within Tumor Microenvironment Affect Neuroinflammation, Tumor and Pain Evolution

Pain can be a devastating experience for cancer patients, resulting in decreased quality of life. In the last two decades, immunological and pain research have demonstrated that pain persistence is primarily caused by neuroinflammation leading to central sensitization with brain neuroplastic alterat...

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Bibliographic Details
Published in:Cancers 2022-04, Vol.14 (9), p.2253
Main Authors: Santoni, Angela, Santoni, Matteo, Arcuri, Edoardo
Format: Article
Language:English
Subjects:
Bone cancer
Cancer
Central nervous system
Chronic pain
Cytokines
Disease
Drug tolerance
Fibroblasts
Growth factors
Hyperalgesia
Immunological tolerance
Inflammation
Leukocytes
Metastases
Morphine
Narcotics
Nervous system
Opioid receptors
Pain
Pain perception
Patients
Quality of life
Review
Skin cancer
Spinal cord
Stromal cells
Trauma
Tumor microenvironment
Tumors
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Summary:Pain can be a devastating experience for cancer patients, resulting in decreased quality of life. In the last two decades, immunological and pain research have demonstrated that pain persistence is primarily caused by neuroinflammation leading to central sensitization with brain neuroplastic alterations and changes in pain responsiveness (hyperalgesia, and pain behavior). Cancer pain is markedly affected by the tumor microenvironment (TME), a complex ecosystem consisting of different cell types (cancer cells, endothelial and stromal cells, leukocytes, fibroblasts and neurons) that release soluble mediators triggering neuroinflammation. The TME cellular components express opioid receptors (i.e., MOR) that upon engagement by endogenous or exogenous opioids such as morphine, initiate signaling events leading to neuroinflammation. MOR engagement does not only affect pain features and quality, but also influences directly and/or indirectly tumor growth and metastasis. The opioid effects on chronic cancer pain are also clinically characterized by altered opioid responsiveness (tolerance and hyperalgesia), a hallmark of the problematic long-term treatment of non-cancer pain. The significant progress made in understanding the immune-mediated development of chronic pain suggests its exploitation for novel alternative immunotherapeutic approaches.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers14092253