How Do Sensory Neurons Sense Danger Signals?

Sensory neurons are activated by physical and chemical stimuli, eliciting sensations such as temperature, touch, pain, and itch. From an evolutionary perspective, sensing danger is essential for organismal survival. Upon infection and injury, immune cells respond to pathogen/damage-associated molecular patterns (PAMPs/DAMPs) through pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs), and produce inflammatory mediators that activate sensory neurons through neuro–immune interactions. Sensory neurons also express TLRs and other PRRs that directly sense danger signals after injury or during infection, leading to pain, itch, or analgesia. In addition to slow-acting canonical TLR signaling, TLRs function uniquely in sensory neurons through non-canonical coupling to ion channels, enabling rapid modulation of neuronal activity. We discuss how sensory neurons utilize TLRs and other PRR pathways to detect danger signals in their environment.