Excitatory and inhibitory neuronal signaling in inflammatory and diabetic neuropathic pain

Abstract

Pain, although unpleasant, is an essential warning mechanism against injury and damage of the organism. An intricate network of specialised sensors and transmission systems contributes to reception, transmission and central sensitization of pain. Here, we briefly introduce some of the main aspects of pain signal transmission, including nociceptors and nociceptive signals, mechanisms of inflammatory and neuropathic pain, and the situation of diabetes-associated neuropathic pain. The role of glia—astrocytes, microglia, satellite glia cells—and their specific channels, transporters and signaling pathways is described. A focus is on the contribution of inhibitory synaptic signaling to nociception and a possible role of glycine receptors in glucose-mediated analgesia and treatment-induced diabetic neuropathy. Inhibitory receptors such as GABAA- and glycine receptors are important contributors to nociceptive signaling; their contribution to altered pain sensation in diabetes may be of clinical relevance, and they could be promising therapeutic targets towards the development of novel analgesics.

Exploring the molecular mechanism of Xuebifang in the treatment of diabetic peripheral neuropathy based on bioinformatics and network pharmacology

“…Persistent inflammation linked to diabetes plays a role in causing nerve damage, potentially worsening DPN. This impact extends to pain perception, involving heightened neuronal excitability, and influences the pain process by altering signaling in neurons ( 62 ). Sustained mild inflammation, initiated by the binding of glucose, lipoproteins, and oxidized proteins to neuronal receptors, plays a substantial role in the development of diabetic neuropathy.…”

Implication of lncRNA MSTRG.81401 in Hippocampal Pyroptosis Induced by P2X7 Receptor in Type 2 Diabetic Rats with Neuropathic Pain Combined with Depression

“…DNP significantly affects the quality of life of patients, but its pathogenesis remains unclear. Currently, apart from duloxetine and gabapentin with limited effectiveness, there is no specific therapy for alleviating DNP [5].…”

Preliminary pharmacokinetics and in vivo studies indicate analgesic and stress mitigation effects of a novel NMDA receptor modulator

“…Pain restricts daily life activities and causes opioid addiction and depression (Dahlhamer et al, 2018; Gureje et al, 1998; Smith et al, 2001). A balanced interplay between the excitatory glutamatergic neurons and GABAergic inhibitory neurons is essential to initiating and maintaining central pain sensitization (Breitinger and Breitinger, 2023). NMDARs play a pivotal role in central pain sensitization, which evolves from activation of neuronal circuits in nociceptive pathways (Aiyer et al, 2018; De Kock and Lavand’homme, 2007; Petrenko et al, 2003).…”