Characterization of Different Types of Excitability in Large Somatosensory Neurons and Its Plastic Changes in Pathological Pain States

Abstract

Sensory neuron types have been distinguished by distinct morphological and transcriptional characteristics. Excitability is the most fundamental functional feature of neurons. Mathematical models described by Hodgkin have revealed three types of neuronal excitability based on the relationship between firing frequency and applied current intensity. However, whether natural sensory neurons display different functional characteristics in terms of excitability and whether this excitability type undergoes plastic changes under pathological pain states have remained elusive. Here, by utilizing whole-cell patch clamp recordings, behavioral and pharmacological assays, we demonstrated that large dorsal root ganglion (DRG) neurons can be classified into three classes and four subclasses based on their excitability patterns, which is similar to mathematical models raised by Hodgkin. Analysis of hyperpolarization-activated cation current (Ih) revealed different magnitude of Ih in different excitability types of large DRG neurons, with higher Ih in Class 2-1 than that in Class 1, 2-2 and 3. This indicates a crucial role of Ih in the determination of excitability type of large DRG neurons. More importantly, this pattern of excitability displays plastic changes and transition under pathological pain states caused by peripheral nerve injury. This study sheds new light on the functional characteristics of large DRG neurons and extends functional classification of large DRG neurons by integration of transcriptomic and morphological characteristics.

Optogenetic recruitment of spinal reflex pathways from large‐diameter primary afferents in non‐transgenic rats transduced with AAV9/Channelrhodopsin 2

“…; Xie et al . ). Consequently, the optogenetics applied to the PNS would never be useful unless they could be selectively applied to a specific group of neurons.…”

“…Among them, a major difficulty is the heterogeneous nature of primary sensory neurons (dorsal root ganglion (DRG) neurons), which are composed of different classes of neurons, each of which has a distinct sensory modality such as nociception and proprioception (Hammond et al 2004;Fang et al 2005;Ruscheweyh et al 2007;Usoskin et al 2015;Li et al 2016;Xie et al 2018). Consequently, the optogenetics applied to the PNS would never be useful unless they could be selectively applied to a specific group of neurons.…”

Atlas of Normal Microanatomy, Procedural and Processing Artifacts, Common Background Findings, and Neurotoxic Lesions in the Peripheral Nervous System of Laboratory Animals

“…While outside the scope of this article, DRG neurons may be further classified based on other morphologic and biochemical features. 22,23 In autonomic ganglia, neurons vary in size from uniformly small ( Figure 3B) to uniformly large (Figure 5) to a mixture of sizes ( Figure 6) depending on the ganglion location and cellular function.…”

CCL2 facilitates spinal synaptic transmission and pain via interaction with presynaptic CCR2 in spinal nociceptor terminals

“…At the same time, we further explained the potential presynaptic analgesic mechanism of CCR2 as an analgesic target. A large number of studies have shown that DRG neurons are divided into different types according to their markers and excitability [ 40 , 41 ]. Therefore, in which neuron subtype CCL2/CCR2 functions is worthy of further investigation.…”