Female mice modeling Rett syndrome exhibit altered pain responses that change as the neurological disorder progresses, according to research published January 20, 2026, by a team at the Faculty of Biological Sciences. The study, appearing in the Journal of Molecular Medicine, found that young mice with mutations linked to the syndrome displayed heightened sensitivity to stimuli, while older mice showed a diminished response to pain.
Rett syndrome is a rare neurodevelopmental disorder primarily affecting girls and women, caused by mutations in the MECP2 gene located on the X chromosome. Individuals with the syndrome experience severe intellectual and motor disabilities, requiring full-time care. Currently, there is no cure.
Researchers conducted a longitudinal study, observing the mice throughout their lifespan. Initially, the mice carrying Mecp2 mutations demonstrated an exaggerated sensitivity to paw stimulation, perceiving even non-painful stimuli as painful. However, as the mice aged and developed more pronounced symptoms of the syndrome, their response shifted, appearing as a lack of sensitivity to pain. “Previous studies considered that people with Rett syndrome were less sensitive to pain than healthy individuals,” the research team noted.
The findings build on earlier work linking MECP2 function to pain sensitivity. A 2010 study published in the American Journal of Medical Genetics investigated atypical pain responses in Rett syndrome and their relationship to specific MECP2 mutations. Recent animal studies have further suggested a connection between MeCP2 and pain perception.
Further research indicates potential therapeutic avenues. A 2020 study demonstrated that chronic treatment with cannabidiolic acid (CBDA) reduced thermal pain sensitivity in male mice and reversed hyperalgesia in a mouse model of Rett syndrome. The ongoing investigation into the mechanisms underlying these altered pain responses may contribute to the development of targeted therapies for managing pain in individuals with Rett syndrome.
