The Effect of Four Weeks of Physical Activity on Rac1 Protein Levels and Plasticity of WDR Neurons in the Dorsal Horn of The Spinal Cord in Mice with Experimental Autoimmune Encephalomyelitis

Changes in the morphology of dendrites and the function of nerve circuits in pain-sensing neurons in the dorsal horn of the spinal cord ultimately lead to neuropathic pain. Increased expression of Rac1 is associated with increased size and density of dendritic spines and increased pain threshold in multiple sclerosis (MS). This study aimed to investigate the effect of four weeks of physical activity in an enriched environment on Rac1 and structural changes of WDR neurons in the dorsal horn of the spinal cord, and pain sensitivity in the chronic course of experimental autoimmune encephalomyelitis (EAE), an animal model used to study the immunopathogenesis of MS.

Thirty female C57BL6 mice were randomly divided into three groups. The first group was induced with MOG35-55 peptide (EAE group), the second group received a saline injection (healthy control group), and the third group, after induction with MOG35-55, was placed in the cage of the enriched environment (group living in enriched environment + EAE). On day 30 post-induction (chronic period of the disease), the formalin test assessed pain sensitivity. Then the mice were anesthetized with ketamine and xylazine, and the spinal cord tissue was removed. Rac1 protein levels were measured by immunohistochemistry. The length and density of dendritic spines were assessed using the Golgi-Cox staining.

Our findings showed that living in an enriched environment significantly reduced RAC1 levels, the length and density of dendritic spines of WDR neurons in the dorsal horn of the spinal cord, and pain sensitivity compared to the EAE group.

Changing the environment and lifestyle to a happy and enriched environment and active lifestyle could reduce pain sensitivity in MS by preventing structural changes in pain-sensing neurons in the dorsal horn of the spinal cord.