The role of TLR2-mediated neuroimmune signal transduction in pathological pain

Biochem Biophys Res Commun. 2026 Apr 14;817:153761. doi: 10.1016/j.bbrc.2026.153761. Online ahead of print.

ABSTRACT

Toll-like receptor 2 (TLR2) acts as a central hub linking nerve injury to immune responses and plays a pivotal role in driving the initiation and persistence of pathological pain. In this review, we systematically outline how TLR2 triggers neuroimmune responses centered in spinal microglia and astrocytes through its recognition of both damage-associated molecular patterns (DAMPs) and exogenous microbial components. We highlight the key signaling pathways modulated by TLR2 activation, including the MyD88/NF-κB pathway that drives transcriptional upregulation of proinflammatory cytokines, and the activation and assembly of p38 MAPK and the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome-events leading to the maturation and release of effector molecules such as interleukin-1β (IL-1β). Collectively, these signaling cascades induce sustained increases in neuronal excitability and alterations in synaptic plasticity, thereby mediating hyperalgesia and chronic pain. By dissecting the TLR2-mediated neuroimmune signaling network, this review provides a comprehensive understanding of the mechanisms by which TLR2 integrates neuroinflammatory responses with neuronal excitability, and explores the therapeutic potential of targeted interventions against TLR2.

PMID:41990452 | DOI:10.1016/j.bbrc.2026.153761