Diverse roles and modulations of IA in spinal cord pain circuits

This review highlights recent findings of different amplitude ranges, roles, and modulations of A-type K+ currents (I-A) in excitatory (GAD67-GFP(-)) and inhibitory (GAD67-GFP(+)) interneurons in mouse spinal cord pain pathways. Endogenous neuropeptides, such as TAFA4, oxytocin, and dynorphin in particular, have been reported to modulate I-A in these pain pathways, but only TAFA4 has been shown to fully reverse the opposing modulations that occur selectively in LIlo GAD67-GFP(-) and LIli GAD67-GFP(+) intemeurons following both neuropathic and inflammatory pain. If, as hypothesized here, Kv4 subunits underlie I-A in both GAD67-GAP(-) and GAD67-GFP(+) interneurons, then I-A diversity in spinal cord pain pathways may depend on the interneuron-subtype-selective expression of Kv4 auxiliary subunits with functionally different N-terminal variants. Thus, I-A emerges as a good candidate for explaining the mechanisms underlying injury-induced mechanical hypersensitivity.

Automated summary

This review highlights recent findings on the amplitude ranges, roles, and modulations of A-type K+ currents (I-A) in excitatory and inhibitory interneurons in mouse spinal cord pain pathways. The study suggests that endogenous neuropeptides may modulate I-A in these pathways, with TAFA4 being the only one that fully reverses the opposing modulations in both neuropathic and inflammatory pain. The review also proposes that the diversity of I-A in spinal cord pain pathways may depend on the expression of Kv4 auxiliary subunits with functionally different N-terminal variants.