Pain is one of many adverse effects of chemotherapy. One type of pain called chemotherapy-induced neuropathic pain can be caused by platinum-based anti-cancer drugs. A new study published in the journal Pain showed promising success in blocking the cause of CINP.

Excruciating Pain from Chemotherapy Addressed in New Study

Platinum-based anti-cancer drugs are used to treat several types of cancer, such as ovarian cancer and lymphoma, but they're especially effective against testicular cancer. The mechanism of drugs revolves in the platinum atom combined with two ammonium molecules and two chloride ions. As a compound, the drugs are negatively charged and only become positive after entering cancer cells. The shift occurs when the chloride ions replace the water molecules in the cells.

Once the water molecules are displaced by the chloride ions, the platinum-based compound attaches to the DNA of the malignant cell. The attachment creates cross-links in the genetic structure that prevents the cell from reading the code. Cancer cells that cannot read the genetic structure fail to function and eventually die.

Oxaliplatin is one many platinum-based anti-cancer drugs widely used to treat colorectal cancer. Unfortunately, the treatment causes numerous side effects, such as headaches, tiredness, redness and swelling of the arms, muscle tenderness, and pain in different parts of the body. Patients can experience numbness in the extremities, burning or shooting in the limbs or feelings of cold or hot in the hands and feet, which are characteristics of the chemotherapy-induced neuropathic pain.

"Thanks to the increased efficacy of cancer treatment… Many of these survivors suffer from long-term side effects of CINP, for which there are no proven strategies for prevention or treatment. This is a huge unmet medical need," said Dr. Daniela Salvemini, the lead author of the study and a professor of pharmacology and physiology at Saint Louis University.

In the study, the researchers examined the oxaliplatin drug and found that more than 60 percent of the patients who were treated by the drug suffered CINP even after the treatment has ended. They investigated how the medication causes severe pain in patients. Analysis revealed that pain associated with the drug was related to an enzyme called adenosine kinase.

Adenosine kinase is an enzyme that catalyzes the transfer of the gamma-phosphate from the adenosine triphosphate, the energy currency of life, to adenosine, a chemical that plays a role in numerous biological processes. Because of its widespread effects in multiple organ systems, clinicians believe that it can be used in pharmacology, such as agents to reduce inflammation.

But the SLU researchers found that higher concentrations of the enzyme in star-shaped cells in the brain and the spinal cord, called astrocytes, and the decreased receptor A3AR, which is responsible for adenosine signaling, created the pain pathway linked to the anti-cancer drug. Using specific agonists, they were able to supplement the signaling property of the A3AR that turned off the pain pathway.

Their findings suggest that the use of A3AR agonists can relieve the patient of chemotherapy pain, which prevents the patient from quitting their therapy.

About Oxaliplatin

Oxaliplatin is often administered through the vein for at least two hours every two weeks. It may be combined with other medications, such as leucovorin, for optimal benefits. The dosage depends on the person's medical condition, body size, and response to the treatment. Since the anti-cancer drug contains platinum, certain precautions must be kept in mind before using it, such as:

- Allergy to platinum: It is a rare condition characterized by a skin rash when wearing certain jewelry, such as a wedding band. The condition can be diagnosed by a patch test for metals and a positive result indicates wedding ring dermatitis. However, some cases of platinum allergy indicate that the person may be allergic to other components of the jewelry, such as nickel or titanium. If the platinum is administered intravenously and the person is allergic, a hypersensitive reaction can cause abdominal cramps, back pain, and complications to the cardiovascular and respiratory systems.

- Kidney problems: Patients who react badly to platinum-based anti-cancer drugs can suffer nephrotoxicity, a phenomenon wherein the components of the medication become toxic to the kidneys. According to a 2015 study, the condition can occur when the platinum triggers cell death in kidneys.

- Blood disorders: Anemia is a blood disorder characterized by the lack of healthy red blood cells or hemoglobin. Chemotherapy, including drugs that contain platinum, can damage both the bone marrow and the kidneys. Cisplatin, carboplatin, and oxaliplatin are platinum-based drugs that can cause anemia as their side effect. Untreated anemia can lead to health complications, such as enlargement of the heart, a severe case of fatigue, and sudden death due to blood loss.

Patients who are advised to take oxaliplatin must discuss the benefits and risk with their doctors. Moreover, patients must detail their medical history and any known underlying health problems before agreeing to a platinum-based medication.

[메디컬리포트=Ralph Chen 기자]