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Monomethyl fumarate inhibits pain behaviors and amygdala activity in a rat arthritis model

Kim, Hyunyounga; Thompson, Jeremya; Ji, Guangchena; Ganapathy, Vadivelb,c; Neugebauer, Volkera,b,*

doi: 10.1097/j.pain.0000000000001042
Research Paper
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Neuroplasticity in the amygdala, a brain center for emotions, leads to increased neuronal activity and output that can generate emotional-affective behaviors and modulate nocifensive responses. Mechanisms of increased activity in the amygdala output region (central nucleus, CeA) include increased reactive oxygen species, and so we explored beneficial effects of monomethyl fumarate (MMF), which can have neuroprotective effects through the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) antioxidant response pathway. Systemic (intraperitoneal) MMF dose-dependently inhibited vocalizations and mechanosensitivity (hindlimb withdrawal reflexes) of rats in an arthritis pain model (kaolin-carrageenan-induced monoarthritis in the knee). Stereotaxic administration of MMF into the CeA by microdialysis also inhibited vocalizations but had a limited effect on mechanosensitivity, suggesting a differential contribution to emotional-affective vs sensory pain aspects. Extracellular single-unit recordings of CeA neurons in anesthetized rats showed that stereotaxic administration of MMF into the CeA by microdialysis inhibited background activity and responses of CeA neurons to knee joint stimulation in the arthritis pain model. Monomethyl fumarate had no effect on behaviors and neuronal activity under normal conditions. The results suggest that MMF can inhibit emotional-affective responses in an arthritis pain model through an action that involves the amygdala (CeA).

Monomethyl fumarate (MMF), which has neuroprotective and antioxidant properties, inhibited behavioral responses and neuronal activity in the amygdala in a rat model of arthritis pain.

aDepartment of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center (TTUHSC), School of Medicine, Lubbock, TX, USA

bCenter of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center (TTUHSC), Lubbock, TX, USA

cDepartment of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center (TTUHSC), Lubbock, TX, USA

Corresponding author. Address: Department of Pharmacology and Neuroscience, Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center (TTUHSC), School of Medicine, 3601 4th St, Lubbock, TX 79430-6592, USA. Tel.: (806) 743-3880; fax: (806) 743-2744. E-mail address: volker.neugebauer@ttuhsc.edu (V. Neugebauer).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Received April 12, 2017

Received in revised form August 07, 2017

Accepted August 11, 2017

© 2017 International Association for the Study of Pain
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