Anesthesiology
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Available treatments for neuropathic pain have modest efficacy and significant adverse effects, including abuse potential. Because oxidative stress is a key mechanistic node for neuropathic pain, the authors focused on the master regulator of the antioxidant response-nuclear factor erythroid 2-related factor 2 (NFE2L2; Nrf2)-as an alternative target for neuropathic pain. The authors tested whether dimethyl fumarate (U.S. Food and Drug Administration-approved treatment for multiple sclerosis) would activate NFE2L2 and promote antioxidant activity to reverse neuropathic pain behaviors and oxidative stress-dependent mechanisms. ⋯ Dimethyl fumarate, a nonopioid and orally-bioavailable drug, alleviated nociceptive hypersensitivity induced by peripheral nerve injury via activation of NFE2L2 antioxidant signaling. Dimethyl fumarate also resolved neuroinflammation and mitochondrial dysfunction-oxidative stress-dependent mechanisms that drive nociceptive hypersensitivity after nerve injury.