BDNF/TrkB signaling pathway and WDR neurons: Core factors inducing central sensitization of neuropathic pain

Abstract

Neuropathic pain is a complex pain syndrome resulting from damage or dis-ease affecting the somatosensory nervous system. Currently, there are no effective treatment options available, which has drawn considerable attention from researchers due to its high prevalence. The mechanisms underlying neuropathic pain are multifaceted, involving structural and functional alterations in central nervous system (CNS), pain signals transduction, and neuroinflammation, with central sensitization recognized as an important mechanism. Central sensitization is characterized by increased neuronal excitability and synaptic plasticity. Brain-derived neurotrophic factor (BDNF) plays a pivotal role in central sensitization induced by nerve injury through its binding to the tropomyosin receptor kinase B (TrkB) receptor. The activation of BDNF/TrkB signaling pathway modulates neuronal synaptic plasticity and enhances the transmission of pain signals. Additionally, the spinal dorsal horn (SDH) wide dynamic range (WDR) neurons act as integrative centers for pain signals, receiving inputs from peripheral nociceptive stimuli and exhibiting heightened excitability in neuropathic pain. Hyperexcited WDR neurons not only respond to central sensitization but also are further intensified by BDNF/TrkB signaling pathway, ultimately amplifying pain perception. This review intends to systematically summarize the interactions between central sensitization, BDNF/TrkB signaling, and WDR neurons, illustrating their potential relationships in neuropathic pain and identifying possible intervention targets, thereby offering new insights and strategies for neuropathic pain relief.