Conserved Expression of Nav1.7 and Nav1.8 Contribute to the Spontaneous and Thermally Evoked Excitability in IL-6 and NGF-Sensitized Adult Dorsal Root Ganglion Neurons In Vitro

Abstract

Sensory neurons respond to noxious stimuli by relaying information from the periphery to the central nervous system via action potentials driven by voltage-gated sodium channels, specifically Nav1.7 and Nav1.8. These channels play a key role in the manifestation of inflammatory pain. The ability to screen compounds that modulate voltage-gated sodium channels using cell-based assays assumes that key channels present in vivo is maintained in vitro. Prior electrophysiological work in vitro utilized acutely dissociated tissues, however, maintaining this preparation for long periods is difficult. A potential alternative involves multi-electrode arrays which permit long-term measurements of neural spike activity and are well suited for assessing persistent sensitization consistent with chronic pain. Here, we demonstrate that the addition of two inflammatory mediators associated with chronic inflammatory pain, nerve growth factor (NGF) and interleukin-6 (IL-6), to adult DRG neurons increases their firing rates on multi-electrode arrays in vitro. Nav1.7 and Nav1.8 proteins are readily detected in cultured neurons and contribute to evoked activity. The blockade of both Nav1.7 and Nav1.8, has a profound impact on thermally evoked firing after treatment with IL-6 and NGF. This work underscores the utility of multi-electrode arrays for pharmacological studies of sensory neurons and may facilitate the discovery and mechanistic analyses of anti-nociceptive compounds.

Inflammatory Process and Role of Cytokines in Inflammation: An Overview

“…These interleukin trigger the factors and antibodies to the site of inflammation (Snapper and Abraham, 2013). Inflammatory conciliators produced throughout inflammation, causes pain through sensation of nociceptors and direct activation of nociceptors (Atmaramani et al, 2020). The main issue with inflammation is not the means by which regularly it begins, but how frequently it fails to decline (Nathan and Ding, 2010).…”

Examining Sodium and Potassium Channel Conductances Involved in Hyperexcitability of Chemotherapy-Induced Peripheral Neuropathy: A Mathematical and Cell Culture-Based Study

“…Chili pepper compound capsaicin was added into the system to trigger a sensory response. Fold change was calculated from natural logarithm of firing rate in line with literature (Atmaramani et al, 2020 ; Negri et al, 2020 ). Percent change described in Table 2 is the number of spontaneous firing neurons after treatment minus the number before treatment over number before treatment.…”

A review of neuroendocrine immune system abnormalities in IBS based on the brain–gut axis and research progress of acupuncture intervention

“…In addition, IL-6 releases the sympathetic brake by suppressing the presynaptic inhibition of norepinephrine release. On the other hand, visceral pain can be evoked after cytokine excitation of enteric neurons (Buckley et al, 2016 ), making cytokines an important cause of visceral pain-mediated IBS (Atmaramani et al, 2020 ).…”

“…It has been reported that the levels of anti-inflammatory cytokines (e.g., IL-10 and transforming growth factor beta) decreased in IBS colon and rectal biopsies (Coëffier et al, 2010 ; Ivashkin et al, 2021 ). Probiotics, as living microorganisms, can modulate the immune system, leading to the upregulation of anti-inflammatory cytokines and growth factors, and can interact with the brain–gut axis by regulating endocrine and neurological functions (Atmaramani et al, 2020 ). Thus, immune factors play an important role in the pathogenesis of IBS as intermediate transmitters or different “links” in the regulation of the neuroendocrine-immune network.…”