researchers from Institute of Neurosciences (IN)−a joint center of the Higher Council for Scientific Research and the Miguel Hernández University (UMH)−discovered in mice how to prevent neuropathic pain associated with chemotherapy in the treatment of colon cancer, one of the most diagnosed tumors. The study, published in the journal Brain, they did this in collaboration with scientists at ESTEVE Pharmaceutical products.
A high percentage of cancer patients treated with chemotherapy develops hypersensitivity to cold and touch in the extremities and mouth. It is what is known as painful neuropathy by chemotherapeutic agents. Its development determines the maximum dose of the administered drug and compromises its efficiency. Sometimes, it can even force the abandonment of the treatment, compromising the survival of the patients.
“The results of our work show that treatment before chemotherapy with a antagonist of the sigma-1 receptor, a key pain control protein, largely prevents the development of these symptom neuropathic diseases, which are associated with the administration of one of the components of chemotherapy: oxaliplatin”, explains the researcher Elvira de la PenaUMH professor and lead author of the study.
A possible strategy against painful neuropathy
O colorectal It is one of the most common tumors and is the second leading cause of cancer death worldwide. Your chemotherapy treatment includes the use of oxaliplatin in combination with other antitumor drugs. in a number High of patients, this compound causes numbness or tingling in the fingers or pain in the hands and feet when touching metal objects, going outside in cold weather, or even when bathing or washing hands. These discomforts can become very disabling and affect the normal performance of daily activities, such as walking or dressing.
O hypersensitivity tactile and thermal in this neuropathy is known to be associated with alterations in a molecular sensor known as the TRPA1 ion channel −discovered by Ardem Patapoutian, recent laureate of Physiology or Medicine−.
“Using biochemical techniques we showed that the TRPA1 channel needs to interact with the sigma-1 receptor, forming a molecular complex, for its correct expression on the surface of neurons”, adds de la Peña. This molecular interaction is the cause of under development of painful symptoms.
The researchers observed that certain molecules, defined as ‘antagonists’ of sigma-1 inhibit TRPA1 function. They then used a experimental model of oxaliplatin neuropathy in mice to find out whether treatment with a sigma-1 antagonist, called S1RA, could prevent pain transmission.
“We found that the rats treated with S1RA during the administration of oxaliplatin normalized their response to painful stimuli”, says the researcher.
We must be cautious when transferring these findings to humans. However, they offer hope that in the future they can be used as a new therapy for painful neuropathy.
“As in any basic research, performed in experimental animals, we must be cautious when transferring these findings to humans. it takes one clinical trial in patients. However, these results are an important step in understanding this pathology and offer the have hope that in the future can be used as a new therapy for the treatment and prevention of these disabling side effects of anticancer treatments”, concludes the researcher Félix Vianaprincipal investigator of the IN and co-author of the study.
In future studies, IN researchers plan to determine whether what they found for oxaliplatin can be generalized to other anticancer agents used to treat cancer. different tumors.
Reference:
Marcotti and others., modulation of TRPA1 by the Sigma-1 receptor prevents oxaliplatin-induced painful peripheral neuropathy. (2022) Brain