Reactive Astrogliosis in an Experimental Model of Fibromyalgia: Effect of Dexmedetomidine

Abstract

To our knowledge, this is the first study which investigates the induction of neuroinflammation in rats using an acidic-saline model of fibromyalgia. It is well known that the hippocampus has a fundamental role in pain perception, and astrocytes play a crucial role in pain signaling. Our aim is to evaluate the ability of dexmedetomidine to attenuate the inflammatory responses induced in astrocytes. In a group of healthy rats, induction of chronic muscle pain by intramuscular injection of 100 µL of acidic saline on days 0 and 5 resulted in peripheral sensitization (measured using the von Frey test) and significant (p < 0.05) increases in IL-1β (160.2 ± 1.1 to 335.2 ± 1.8), IL-6 (100.1 ± 1.4 to 202.4 ± 1.1), and TNF-α (60.0 ± 0.7 to 115.5 ± 1). Light and electron microscopy revealed degenerative changes in the hippocampus and reactive astrogliosis. Immunohistochemistry showed increased expression of glial fibrillary acid protein and inducible nitric oxide synthase. Surprisingly, treatment with a single dose of an α₂-adrenergic agonist, dexmedetomidine (5 µg/kg i.p.), attenuated these changes. This trial suggests that dexmedetomidine possibly directly acts on astrocytes, and a peripheral action is also suggested.

Long-lasting reflexive and nonreflexive pain responses in two mouse models of fibromyalgia-like condition

“…Results revealed that that RIM3, RIM4 and ASI models lead to transient spinal cord gliosis up to 4 weeks postinduction, whereas RIM6 pattern administration results in longer-lasting astro- and microgliosis up to 6 weeks. These results are consistent with previous results obtained in the short term in rat models 17 , 24 , 43 , but to our knowledge, this is the first study describing spinal cord gliosis up to 6 weeks in an RIM6 mouse model and up to 4 weeks in the ASI. Spinal cord gliosis is known to play a pivotal role in the pathogenesis of chronic pain, and glial activation is now recognized as a powerful mechanism underlying the pathogenesis of chronic pain 44 .…”

Neuroinflammation: An Integrating Overview of Reactive-Neuroimmune Cell Interactions in Health and Disease

“…Certain systemic and organ-specific autoimmune diseases, rheumatic mainly, can cause neuroinflammation. Fibromyalgia [ 4 ], destructive joint diseases [ 6 ], and systemic lupus erythematosus [ 3 ] are a few examples. Neurodegeneration studies suggest that peripheral infection might be related to onset and progression of age-related neurodegeneration [ 24 ].…”

Organoprotective effects of the α2-adrenoreceptor agonist dexmedetomidine (literature review)

“…Удивительно, но лечение одной дозой α 2 -адренергического агониста дексмедетомидина (5 мкг/кг) смягчило эти изменения. Это исследование предполагает, что дексмедетомидин, возможно, непосредственно воздействует на астроциты, а также предполагается и его периферическое действие [22].…”