New pathways identified to reduce pain and depressive symptoms associated with fibromyalgia

Fibromyalgia is a chronic condition that affects between 2% and 6% of the global population. It is characterised by widespread, persistent pain, often accompanied by fatigue, sleep disturbances, cognitive difficulties and affective symptoms. Despite its high prevalence, particularly among women, the mechanisms that contribute to the development and persistence of the condition are still not fully understood.

To investigate potential factors involved in these symptoms, a research group from the INc-UAB and IR Sant Pau worked with male and female mice in which symptoms resembling those of fibromyalgia were induced. The animals showed increased sensitivity to touch, heat and cold, as well as behaviours associated with a depressive state.

The team sought to investigate the role of oxidative stress and inflammation in these processes and treated the animals with dimethyl fumarate or cobalt protoporphyrin IX, two compounds capable of strengthening the body's defence systems against oxidative stress, although they act through different mechanisms. According to the results, both treatments reduced pain hypersensitivity and improved behaviours associated with a depressive state. However, dimethyl fumarate produced a stronger and more rapid response.

The researchers also analysed what was happening at the molecular level in the animals' brains and spinal cords. They found that the treatments modulated different mechanisms involved in redox balance, inflammation and neuronal plasticity. These effects were not exactly the same across all regions of the nervous system or with both treatments. Dimethyl fumarate produced a broader molecular response, whereas cobalt protoporphyrin IX showed a more specific profile.

According to the researchers, these differences suggest that nociplastic pain, the type of pain that occurs when the nervous system processes signals in an altered way, as happens in fibromyalgia, is not associated with a uniform disruption of redox balance throughout the nervous system. Instead, there may be specific changes depending on the brain or spinal cord region involved. The characterisation of these differences in the study could contribute to a better understanding of the mechanisms underlying pain and the emotional disturbances observed in patients.

The study also took sex differences into account. Both males and females responded to both treatments, both in terms of pain hypersensitivity and behaviours associated with a depressive state. However, for some pain-related measures, recovery was slower in females.

“Our results suggest that strengthening the body's natural defence mechanisms against oxidative stress could be a promising approach for modulating both pain and affective disturbances associated with fibromyalgia. In addition, the fact that one of the compounds studied, dimethyl fumarate, is already used clinically to treat multiple sclerosis opens up a particularly interesting translational perspective,” explains Dr Olga Pol, coordinator of the study and researcher at the INc-UAB and IR Sant Pau.

The authors point out that the results were obtained in an animal model and therefore cannot be directly extrapolated to people with fibromyalgia. Nevertheless, they could help open new avenues of research into mechanisms related to antioxidant cellular protection as potential targets for the development of new treatments for chronic pain and associated affective symptoms.

Reference: Negrini-Ferrari, S. E., Wang, W., & Pol, O. (2026). Dimethyl Fumarate and Cobalt Protoporphyrin IX Inhibit Fibromyalgia-like Pain by Modulating Region-Specific Redox Pathways. Antioxidants, 15(9), 1080. https://doi.org/10.3390/antiox15091080