# Exploring the Role of Heat Shock Proteins in Neuroimmune Modulation in Rheumatoid Arthritis: Insights from a Rat Model

## TL;DR

This study explores how heat shock proteins (HSPs) influence neuroimmune interactions in rheumatoid arthritis using a rat model, suggesting they could be a new treatment target.

## Contribution

The study reveals that ketamine modulates HSP expression in the spinal cord of RA rats, linking HSPs to neurogenic inflammation and neurogenesis.

## Key findings

- Hsp60, 70, and 90 expression levels changed significantly in the spinal cord of RA rats.
- Ketamine modulates spinal cord HSPs, affecting neurogenic inflammation and adult neurogenesis in RA rats.
- HSPs show potential as therapeutic targets due to their immunomodulatory and neuroimmune roles.

## Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease affecting the joints, with neurogenic inflammation involving the nervous system being a hallmark of the condition. Treatments include medications such as disease-modifying antirheumatic drugs (DMARDs), corticosteroids, and biologics targeting inflammatory pathways. Yet, these treatments are not curative for RA. Heat Shock Proteins (HSPs) are molecular chaperones with immunoregulatory properties; however, their role is not yet fully understood, as these molecules may play a dual, pro- and anti-inflammatory role. In this study, we evaluated the protein expression levels of HSPs 27, 60, 70, and 90 in the synovial membrane and spinal cord of the RA rats’ model to determine their roles during the disease course, both on the neurological and immunological levels. Furthermore, HSP levels have been evaluated in the spinal cord of control and RA rats’ model after high and low doses of ketamine injection. Significant changes in Hsp60, 70, and 90 expression levels were observed only in the spinal cord of RA rats. We demonstrated that blocking N-methyl-D-aspartate receptors with ketamine can modulate spinal cord HSPs expression in RA rats and subsequently impact neurogenic inflammation and adult neurogenesis. This suggests that HSPs may be a promising target for RA treatment due to their complex immunomodulatory effects and potential interactions with the nervous system. Further research is needed to explore their therapeutic potential and develop effective interventions for RA.