Abstract
BackgroundRecent studies have demonstrated a role for spinal p38 MAP kinase (MAPK) in the development of chronic inflammation and peripheral arthritis and a role for GABA in the inhibition of p38 MAPK mediated effects. Integrating these data suggests that GABA may play a role in downregulating mechanisms that lead to the production of proinflammatory agents such as interleukin-1, interleukin-6, and matrix metalloproteinase 3 – agents implicated in the pathogenesis of rheumatoid arthritis (RA). Genetic studies have also associated RA with members of the p38 MAPK pathway.HypothesisWe propose a hypothesis for an inefficient GABA signaling system that results in unchecked proinflammatory cytokine production via the p38 MAPK pathway. This model also supports the need for increasing research in the integration of immunology and neuroscience.
Highlights
Recent studies have demonstrated a role for spinal p38 MAP kinase (MAPK) in the development of chronic inflammation and peripheral arthritis and a role for gamma-aminobutyric acid (GABA) in the inhibition of p38 MAPK mediated effects
The impact of an immune response on the nervous system has long been apparent, with multiple sclerosis (MS), myasthenia gravis (MG), and neuropsychiatric manifestations of systemic lupus erythematosus serving as examples
We propose a model in which gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter of the central nervous system (CNS), may downregulate p38 MAPK activity to reduce peripheral production of proinflammatory cytokines in joints affected by rheumatoid arthritis (RA)
Summary
Recent studies have demonstrated a role for spinal p38 MAP kinase (MAPK) in the development of chronic inflammation and peripheral arthritis and a role for GABA in the inhibition of p38 MAPK mediated effects. A recent article reported that inhibiting spinal cord p38 MAP kinase (MAPK) reduced joint inflammation in the rat model of RA by an unknown mechanism [4]. Somatic afferent pain signals received in the spinal cord result in stressinduced kinase release, causing efferent signals that direct mediators of inflammatory response.
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