Functional subgroups of rat and human sensory neurons: a systematic review of electrophysiological properties

Abstract

Sensory neurons are responsible for the generation and transmission of nociceptive signals from the periphery to the central nervous system. They encompass a broadly heterogeneous population of highly specialized neurons. The understanding of the molecular choreography of individual subpopulations is essential to understand physiological and pathological pain states. Recently, it became evident that species differences limit transferability of research findings between human and rodents in pain research. Thus, it is necessary to systematically compare and categorize the electrophysiological data gained from human and rodent dorsal root ganglia neurons (DRGs). In this systematic review, we condense the available electrophysiological data defining subidentities in human and rat DRGs. A systematic search on PUBMED yielded 30 studies on rat and 3 studies on human sensory neurons. Defined outcome parameters included current clamp, voltage clamp, cell morphology, pharmacological readouts, and immune reactivity parameters. We compare evidence gathered for outcome markers to define subgroups, offer electrophysiological parameters for the definition of neuronal subtypes, and give a framework for the transferability of electrophysiological findings between species. A semiquantitative analysis revealed that for rat DRGs, there is an overarching consensus between studies that C-fiber linked sensory neurons display a lower action potential threshold, higher input resistance, a larger action potential overshoot, and a longer afterhyperpolarization duration compared to other sensory neurons. They are also more likely to display an infliction point in the falling phase of the action potential. This systematic review points out the need of more electrophysiological studies on human sensory neurons.

Satellite Glial Cells: Morphology, functional heterogeneity, and role in pain

“…Sensory neurons in the DRG are extremely diverse depending on their size, expression, and signaling activity (Körner and Lampert, 2022 ). Because each neuron has a sheath consisting of SGCs, the diversity of neurons is accompanied by a variety of SGCs consisting of this sheath.…”

Non-nociceptive and nociceptive-like trigeminal Aβ-afferent neurons of rats: Distinct electrophysiological properties, mechanical and chemical sensitivity

“…There are a number of advantages with our approach over previous studies. Previous studies used in vivo intracellular recordings and demonstrated distinct electrophysiological properties of Aβ-afferent neurons in DRGs and their response to mechanical stimulation applied to the periphery ( Korner and Lampert 2022 ). However, in vivo intracellular recordings provided limited information about ion channels involved in mechanical and chemical sensitivity of Aβ-afferent neurons.…”

“…The somas of somatosensory afferents are located in the dorsal root ganglions (DRGs) and trigeminal ganglions (TGs), which vary in sizes with small-to medium-diameter neurons giving rise to C- and Aδ-afferents and large-diameter neurons giving rise to Aβ-afferents ( Vermeiren et al 2020 ). Functions of somatosensory afferents are commonly studied by making electrophysiological recordings from the somas of these nerves or afferent neurons ( Korner and Lampert 2022 ). C-and Aδ-afferent neurons have been extensively studied, and most of them are involved in nociception induced by high-intensity mechanical, thermal, and chemical stimulation ( Korner and Lampert 2022 ; Lawson et al 2019 ; Vermeiren et al 2020 ), although some Aδ- and C-afferents are low threshold mechanoreceptors (LTMRs) for sensing touch ( Djouhri 2016 ; Li et al 2011 ).…”

“…Functions of somatosensory afferents are commonly studied by making electrophysiological recordings from the somas of these nerves or afferent neurons ( Korner and Lampert 2022 ). C-and Aδ-afferent neurons have been extensively studied, and most of them are involved in nociception induced by high-intensity mechanical, thermal, and chemical stimulation ( Korner and Lampert 2022 ; Lawson et al 2019 ; Vermeiren et al 2020 ), although some Aδ- and C-afferents are low threshold mechanoreceptors (LTMRs) for sensing touch ( Djouhri 2016 ; Li et al 2011 ). In contrast, Aβ-afferent neurons are largely understudied and their functions are often oversimplified as being LTMRs for sensing touch ( Djouhri and Lawson 2004 ; Lawson et al 2019 ), and the potential involvement of Aβ-afferent neurons in nociception is largely neglected.…”

Electrophysiology of nociception: understanding of signaling pathways forms a basis for potential treatment

“…Systematic review of available literature identified five grouping criteria for classification of rat DRGs. No sufficient number of data are available for human DRG neurons; however, it is clear that findings from rat neurons cannot be transferred offhand to the human system [8]. Further functional data on human sensory neurons are needed to facilitate progress in development of pain treatment.…”