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. Author manuscript; available in PMC: 2017 Dec 1.
Published in final edited form as: Trends Neurosci. 2016 Nov 12;39(12):862–879. doi: 10.1016/j.tins.2016.10.003

Figure 2. Sources of nitroxidative species after tissue injury.

Figure 2

Principal sources of nitroxidative species include NADPH oxidase (NOX), nitric oxide synthase (NOS), and electron leakage from the mitochondrial electron transport chain (mETC). The NOX1, 2, and 4 isoforms are differentially expressed across cell types and tissues after injury. NOX1-derived reactive oxygen species induce enhance Transient Receptor Potential (TRP) V1 activity in dorsal root ganglia (DRG) neurons. NOX2 activity in macrophages and microglia drives mRNA expression of proinflammatory cytokines (PIC) in DRG the spinal dorsal horn. NOX4 expression at the site of peripheral nerve injury decreases expression of myelin proteins (MP). The three NOS isoforms—NOS1 (neuronal), 2 (inducible), and 3 (endothelial)—are also differentially expressed by cell type. In abnormal pain states, N-methyl-D-aspartate receptors (NMDARs) are activated, resulting in calcium influx and activation of NOS1. Transcription of NOS2 is initiated by Toll like receptors (TLRs). These enzymes and processes have a well-established role in pathological pain.