There is growing evidence that many non-nerve cells play an important role in the pathogenesis and regulation of pain. Cancer cells are one of the non-nerve cells that release neuromodulatory substances near pain receptors to regulate the activity of nociceptive neurons, thereby promoting or weakening pain sensations. Studies have shown that cancer cells can produce and secrete some biologically active substances that activate pain receptors in the cancer microenvironment, such as H+, brady hormones, endothelin, PG, protease, etc., to sensitize pain; cancer cells also secrete nerve growth factor and vascular endothelial growth factor, on the one hand, induce nerve fiber growth, excessive innervation of cancer tissue, promote pain, on the other hand, can increase the sensitivity of pain receptors, produce pain hypersensitivity reactions. These will aggravate the pain or feeling of pain in tumor patients, and even affect the analgesic effect of the drug.
Ji, R.R., A. Chamessian, and Y.Q. Zhang, Pain regulation by non-neuronal cells and inflammation.? Science, 2016. 354(6312): p. 572-577.
Cancer-related pain is a complex pain state that depends on the regulation of pain by both the tumor and the body, involves a variety of mechanisms such as inflammation, neuropathy, and compression, and constantly changes as the condition progresses. For example, in the early stages of the disease, the degree of pain caused by cancer is still mild, at which point the body may simultaneously produce a series of biological mediators that, as the tumor develops, positively or reversely regulate pain sensitivity.