Chronic pain is the most common health condition globally and one of the leading causes of disability, particularly among women. It is frequently accompanied by mental health problems that exacerbate patients’ suffering and severely affect their daily activities, family life and social relationships. This is the case in conditions such as rheumatoid arthritis, osteoarthritis and fibromyalgia, which often involve what is known as nociplastic pain and central sensitisation, where physical damage does not correspond to the level of pain experienced. Current treatments are often insufficient, leaving many patients with complex pain conditions and difficulties in emotional regulation that reduce their quality of life and may lead to self-medication with alcohol to cope with pain and distress.

Recent research has highlighted the importance of the connection between the body –particularly the gut – and the brain in explaining conditions such as depression and anxiety. These same connections may also play a crucial role in the development and maintenance of pain, as proposed in PainGutPFC. Previous studies by the UV team, in both animal models and humans, have shown that pain significantly alters the brain’s reward system, which can lead to negative emotions and cognitive problems. These changes may also promote unhealthy behaviours, such as excessive alcohol consumption, which in turn can worsen pain, creating a vicious cycle that is difficult to break.

Lucía Hipólito, professor in the Department of Pharmacy and Pharmaceutical Technology and Parasitology at the University of Valencia and coordinator of the project, explains: “This initiative addresses the problem using a translational strategy – that is, by combining preclinical animal studies and clinical studies in humans in parallel, with a strong gender-based approach that recognises the significant differences between men and women in pain experience and treatment response”.

The findings are expected to support the development of targeted therapies and personalised medicine approaches focused on psychological strategies and holistic health, leading to faster and more sustained relief from chronic pain, reduced reliance on medication, and a lower burden of associated emotional problems such as anxiety, depression and self-treatment through excessive alcohol consumption.

Gut microbiota markers

Within the framework of the project, the Microbiome and Innovation in Nutrition and Health Group (Innobiome) at IATA-CSIC contributes its expertise in studying the gut microbiome and its relationship with health. Its work focuses on identifying gut microbiota markers associated with chronic pain and behavioural disorders, as well as on developing microbiome-based strategies with the potential to improve this pathological condition.

The group investigates how the microbiome interacts with environmental factors such as diet and stress, as well as with the human body itself, influencing the immune, endocrine and nervous systems and modulating both physical and mental health. “The group’s contribution is aimed at developing new microbiome-based diagnostic, preventive and therapeutic solutions in order to promote health from a holistic perspective”, explains the IATA team.

In addition to Lucía Hipólito, the research team at the University of Valencia includes Miguel Ángel Serrano, Noemí Sanmiguel, Ana Polache and Vicente Herranz. The project also involves Jorge Fragío (Valencia General University Hospital Consortium, HGUV), Ana Agustí and Marina Romaní (IATA-CSIC). The European consortium is completed by the University of Picardie Jules Verne (France), the Grenoble Alpes University and the Grenoble Institute of Neurosciences (France), and the Maj Institute of Pharmacology of the Polish Academy of Sciences (Poland). Funding has been provided through ERA-Net NEURON, a European international collaborative research programme.