In order to explain why pain occurs due to artemisinin therapy, I must explain to you in detail the complete mechanism of pain in cancerous diseases and all the characteristics of cancer that are associated with pain. We must also focus on classical anticancer protocols such as chemotherapy and radiation and analyze their impact on the development of pain due to their constant use and greater use compared to the alternative method of artemisinin.
Cancer occurs when cells in our body accumulate enough mutations and disrupt regulatory factors in the cellular environment. These cells will continue to divide, regardless of the level of cell density in the environment in which they are located. Cancer cells have managed to overcome the status of extinction and in that way malignant cells achieve the status of immortality. These cells will continue their local proliferation, depriving healthy cells of their blood supply, taking blood as a non-functional organ in the body and consuming huge amounts of energy.
Cancer cells will at some point acquire the ability to penetrate the basement membrane and thus allow themselves to invade other distant parts of the body, a process called metastasis. These cells will repeat the same pattern in a distant area of the body, multiplying by stimulating anginogenesis to provide enough blood in nutrients and fuel for their unbridled metabolic activity. Healthy cells deprived of these ingredients will also have reduced functions and endangered survival. All these events of carcinogenic activity can be observed through the following physical results: increase in the external mass of the tumor due to its spread and increase in the mass of tumor cells, increase in the internal mass due to compression and cell development and as a result severe pain due to neurological deficit.
Cancerous cells, whether benign or malignant, result in abnormal growth and development. If the tumor cells are located on the skin or near the outer parts of the body, they can also spread externally. If the mass of tumor cells is in the internal part and since it does not have an expandable nature due to our internal barriers in the body, the mass of tumor cells will manifest as a compression syndrome. This space occupied by the lesion will result in a compression syndrome, for example in brain tumors, the mass will be compressed in a certain area of the brain, by pressing on blood vessels, neurons and long surrounding tissue. The result of this process will be a local neurological deficit and pain. Healthy cells will be prevented from sufficient blood flow and will eventually begin to die, creating space for further spread of cancer. If compression occurs in the lungs, it will cause difficulty breathing. Compression in the bones, as in bone cancer, causes deformity in the bones, unbearable pain due to stretching or compression of the bone cells.
Healthy cells are fighting a constant battle to supply blood and nutrients to cancer cells. Cancer cells have a higher degree of metabolic activity due to continuous division. These cells will induce the growth of blood vessels through a process called anginogenesis. Through this dilation of blood vessels, normal cells are deprived of the supply of nutrients, which is manifested through the dysfunction of certain organs, and also leads to certain clinical abnormalities in the body. Relevant markers of organ function will also show abnormal values.
Since cancer cells use a huge part of cellular resources, the patient’s body will begin to lose weight in a short time with the accelerated loss of energy. The immune system of cancer patients is very endangered, leaving the organism very susceptible to diseases, and it will also not be able to fight against neoplastic cells, leaving a very large space for further development and progression of cancer.
75% of the pain caused by cancer is attributed to the disease itself. The pain is related primarily and is caused by compression of the surrounding tissue and pressure nerve endings and further by transmitting painful signals to the brain. Also, the death of certain cells can cause pain. If the cancer is located near the surface of the body or on the surface itself, the pain will be localized due to the nature of the spread of the nerves. On the other hand, if the tumor spreads within one of the internal organs, the pain is usually not exactly localized and spreads to other parts of the body that are far from the original location. Since pain is mainly related to the activity and size of tumor cells, its presence may be directly related to increased tumor activity, but this may not be the rule with every onset of pain.
Patients undergoing treatments such as radiation or chemotherapy may experience post-procedural pain, which is caused by the effects of radiation and chemotherapy on healthy cells. In that case, normal cells are damaged due to the therapeutic process, which results in pain due to damage to the neurons themselves.
When cancerous or healthy cells are injured in the therapeutic process, they release cytokines that act as nociceptive stimulants on nerve endings, stimulating pain signals. This is the reason why some people may experience pain after post chemo or radiotherapy. With quality analgesics, pain can be well controlled in about 90% of cases. It is important to note that pain can also be modulated in different perceptions and tolerances in patients, which explains why different people respond differently to the same level of pain. In cancer patients, most of them are under the influence of the stigma of whether they will fail or fall into deep helplessness. In these cases, deep depression occurs in patients with cancer and this condition greatly affects the modulation of pain perception.
Some patients, in addition to very high pain, experienced increased levels of tumor markers due to chemotherapy treatment. This phenomenon is not uncommon. Tumor markers grow mainly in correlation with increased tumor activity, but this should not be equated with the ineffectiveness of chemotherapy. In many cases, these phenomena were directly related to the effectiveness of chemotherapy. Due to some scientific research on colon cancer that has metastasized to other organs due to the action of chemotherapy, there was an increased level of tumor markers, but after some time there was reduction of tumor markers and also to a reduction in tumor volume and metastasis.
Researchers are currently working on an explanation of this phenomenon described above. Before starting chemotherapy, cancer cells function in a balanced way. Their growth limits the blood supply. As the growth of cancer cells accelerates, the blood supply becomes a limiting factor, which goes beyond angiogenesis to provide nutrients and meet the metabolic requirements of cancer. The mass of the cells will continue to grow and the cells that are in the center of the mass will slowly be deprived of the blood supply, which results in the death of the cells in the tumor nucleus. The tumor mass will decrease over time, which will provide space for the development of new cells and their growth. The cycle will continue, and in the process the body will be deprived of all nutrients and energy.
The same is the case with the successful action of some anticancer therapy. When using the anticancer drug artemisinin, some cancer cells die, releasing cytokines that, as mentioned above, stimulate nerves and produce pain signals, and by reducing the population of cancer cells, its activity increases, and this action automatically leads to increased levels of tumor markers in the body. . Also, this activity of dying gives more space for increased development of new cells, and this action can compress the surrounding areas by pressing the nerve endings, stimulating additional pain. When this therapy reaches the optimal level, that is, when more cancer cells are destroyed than the cancer manages to produce, there is a sudden drop in tumor markers and a decrease in tumor development due to the action of artemisinin. Also, in some initial results before reaching this level, we have the case that the volume of the cancer did not decrease, but there is a decrease in the compression or density of the tumor itself. Over time, the action of aretimsinin on the tumor due to reduced compression, increased death of cancer cells in relation to their re-production leads to a decrease in volume and at the same time to a reduction in pressure on nerve endings and reduced cytokine release resulting in reduced pain.