They identify a possible therapeutic target to treat chronic pain in old age

According to some estimates, the therapies available today to treat pain fail in fifty percent of patients over sixty years of age. In addition, some treatments generate numerous adverse side effects.

Scientists have discovered a new therapeutic target to treat chronic pain in older adults by inhibiting a protein that controls the excitability of certain neurons.

The team that made the discovery includes Diego N. Messina, from the National University of Cuyo (UNCUYO), Cristian Acosta, researcher at the National Council for Scientific and Technical Research (CONICET) in the Laboratory of Neurobiological Studies of the Institute of Histology and Mendoza Embryology (IHEM, dependent on CONICET and UNCUYO) and Emanuel D. Peralta, also from IHEM, all of these entities in Argentina.

Using a preclinical model of normal female laboratory rats – the sex of the animals was intentionally chosen by the scientists due to the high level of prevalence of the pathology studied – the team of researchers analyzed the role of the Nav1.8 and ASIC3 proteins, related to chronic pain, and discovered that its expression changes with age, which could partly explain why certain treatments that work for young animals do not work in aged animals. “There is a whole family of molecules present in sensory neurons involved in the detection of harmful stimuli that, when they begin to function abnormally, cause pain. We focus on Nav1.8, which is from a family of sodium ion channels, and on ASIC3, which is a receptor – also an ion channel – sensitive to extracellular acid,” explains Acosta.

Both molecules control the excitability of primary afferent neurons, specialized in detecting sensations such as temperature, touch and pain. “We found that there are differences in the expression of these molecules between the group of young animals and that of aged animals. Also, during the experiment, once chronic inflammation was induced, we observed that its expression changed again and that the condition is much more persistent and prevalent in geriatric animals, which also have a slower recovery,” he details.

The research team performed a pharmacological intervention to block the Nav1.8 and ASIC3 channels, and found that the treatment was effective for both groups, but what is new is that the treatment carried out on ASIC3 was more effective in the aged group than in the young group. , suggesting that the inhibition of this molecule could be a more effective alternative for chronic pain in old age than traditional anti-inflammatory drugs. “This is a target that is not explored today, that is, there is no drug on the market at this time that is directed against that molecule, and what we propose in this study is that this is a new therapeutic target that would have more effectiveness in the aging population,” explains the researcher.

Cristian Acosta, Diego Messina and Emanuel Peralta, authors of the work. (Photo: CONICET / UNCUYO)

The study provides new preclinical evidence on the importance of establishing therapeutic strategies that act on specific proteins that are differentially expressed in different age groups. “We will continue exploring new targets, that is, other molecules that are also part of this system and have the same effect, trying to detect and characterize new therapeutic targets and demonstrate the effectiveness of specific treatments,” Acosta concludes.

The study is titled “Complex alterations in inflammatory pain and analgesic sensitivity in young and aging female rats: involvement of ASIC3 and Nav1.8 in primary sensory neurons.” And it has been published in the academic journal Inflammation Research. (Source: Leonardo Fernández / CONICET. CC BY 2.5 AR)