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The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice
Published on: July 16, 2014
EAE models of neuropathic pain in multiple sclerosis do not require pertussis toxin
Sydney R Lamerand1, Paramita Basu2, Nina E Gakii2
1Department of Anesthesiology and Perioperative Medicine, Department of Pharmacology, Pittsburgh Center for Pain Research, and Pittsburgh Project to end Opioid Misuse, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Center for Neurosciences at the University of Pittsburgh, Pittsburgh, PA, USA.
Background:
Experimental autoimmune encephalomyelitis (EAE) is a preclinical model of multiple sclerosis (MS), typically induced with two inoculations of myelin oligodendrocyte glycoprotein (MOG35-55) emulsified in complete Freund's adjuvant (CFA), and supplemented with pertussis toxin (PTX). Although PTX has been considered essential, recent studies suggest that EAE pathology can develop without it.
Objectives:
Indices of clinical disease and neuropathic pain were evaluated in a conventional model of EAE that included PTX (EAE-PTX) and one that lacked PTX (EAE-nPTX), as well as in multiple control groups that lacked MOG35-55 (CFA-PTX and CFA-nPTX).
Methods:
A battery of behavioral tests were used to evaluate motor dysfunction and hypersensitivity to mechanical, cold, and heat stimuli with a repeated-measures design in male and female C57BL/6 mice. One month after the first EAE inoculation, fluoromyelin staining was used to evaluate demyelination in spinal cord, cortex, and peripheral nerve, while ATF3 was used as a marker of injury in sensory neurons of lumbar L4-L5 dorsal root ganglia (DRG).
Results:
Compared to CFA-PTX and CFA-nPTX controls, both EAE-PTX and EAE-nPTX groups developed motor dysfunction, behavioral hypersensitivity, and demyelination in ventral spinal cord but not cortex. Spinal demyelination was greater in EAE-nPTX than in EAE-PTX. ATF3 was detected in lumbar DRG of all EAE and CFA control groups, suggesting that systemic inflammation, rather than MOG35-55-driven neuropathology, contributes to neuron damage.
Conclusions:
PTX is not required for the manifestation of motor dysfunction and neuropathic pain in MOG35-55-based EAE models. Newer EAE-nPTX models have the distinct advantage of mimicking MS disease while avoiding confounding effects of pertussis toxin.
Insights
Pertussis toxin (PTX) is not essential for inducing experimental autoimmune encephalomyelitis (EAE) or neuropathic pain in mouse models. Newer EAE models without PTX offer a clearer view of multiple sclerosis (MS) pathology.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Experimental autoimmune encephalomyelitis (EAE) is a key preclinical model for studying multiple sclerosis (MS).
- Traditionally, EAE induction relies on myelin oligodendrocyte glycoprotein (MOG35-55) with complete Freund's adjuvant (CFA) and pertussis toxin (PTX).
- Emerging evidence questions the necessity of PTX in EAE development.
Purpose of the Study:
- To compare clinical disease and neuropathic pain indices in EAE models with (EAE-PTX) and without (EAE-nPTX) PTX.
- To evaluate control groups lacking MOG35-55 (CFA-PTX and CFA-nPTX).
- To assess the role of PTX in EAE pathogenesis and neuropathic pain.
Main Methods:
- Utilized a battery of behavioral tests to assess motor dysfunction and hypersensitivity in male and female C57BL/6 mice.
- Employed fluoromyelin staining to evaluate demyelination in the spinal cord, cortex, and peripheral nerves.
- Used ATF3 as a marker for neuronal injury in dorsal root ganglia (DRG).
Main Results:
- Both EAE-PTX and EAE-nPTX groups exhibited motor dysfunction, hypersensitivity, and spinal cord demyelination compared to controls.
- Spinal demyelination was more pronounced in the EAE-nPTX group than in the EAE-PTX group.
- ATF3 expression in DRG across all groups suggested systemic inflammation, not MOG35-55, as a contributor to neuron damage.
Conclusions:
- Pertussis toxin (PTX) is not required for inducing motor deficits and neuropathic pain in MOG35-55-induced EAE.
- EAE models lacking PTX (EAE-nPTX) effectively replicate MS pathology without confounding factors.
- These PTX-free models provide a more refined approach to studying MS.
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