Properties and Differential Expression of H+ Receptors in Dorsal Root Ganglia: Is a Labeled-Line Coding for Acid Nociception Possible?

Abstract

Pain by chemical irritants is one of the less well-described aspects of nociception. The acidic substance is the paradigm of the chemical noxious compound. An acidic insult on cutaneous, subcutaneous and muscle tissue results in pain sensation. Acid (or H⁺) has at least two main receptor channels in dorsal root ganglia (DRG) nociceptors: the heat receptor transient receptor potential vanilloid 1 (TRPV1) and the acid-sensing ionic channels (ASICs). TRPV1 is a low-sensitivity H⁺ receptor, whereas ASIC channels display a higher H⁺ sensitivity of at least one order of magnitude. In this review, we first describe the functional and structural characteristics of these and other H⁺-receptor candidates and the biophysics of their responses to low pH. Additionally, we compile reports of the expression of these H⁺-receptors (and other possible complementary proteins) within the DRG and compare these data with mRNA expression profiles from single-cell sequencing datasets for ASIC3, ASIC1, transient receptor potential Ankiryn subtype 1 (TRPA1) and TRPV1. We show that few nociceptor subpopulations (discriminated by unbiased classifications) combine acid-sensitive channels. This comparative review is presented in light of the accumulating evidence for labeled-line coding for most noxious sensory stimuli.

Keywords: ASIC; DRG; TRP channels; acid; nociceptor; pain; proton.