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Figure 2: Role of NHE1 in intracellular pH regulation and nociception. In inflammatory pain, intracellular acidosis generated from tissue damage at the periphery, as well as from neurotransmitter release at the spinal cord, is counterbalanced by NHE1 contained in the nociceptive fibers. When amiloride or its derivates inhibit NHE1, an excess of intracellular hydrogen ions is accumulated in such a way that increases nociceptive fibers activity and consequently pain intensity. ASICs: acid-sensingion channels, DRG: dorsal root ganglia, NCX: Na+/Ca2+ exchanger, NHE1: Na+/H+ exchanger 1, and TRPV1: transient receptor potential cation channel subfamily V member 1.