Microbes and pain

Abstract

Microbial infections are often painful. Pain is a defense mechanism that alerts organisms to threats and is mediated by nociceptors, first described by Charles Sherrington in 1906 as the sensory afferent neurons that induce withdrawal reflexes in response to noxious stimuli [1]. Nociceptors densely innervate barrier tissues that interface with the environment, including the skin, lungs, urinary tract, and gut, and deeper tissues such as the joints, bones, and meninges. Nociceptor neurons express receptors such as transient receptor potential (TRP) channels that are gated to detect noxious/harmful stimuli including heat, cold, and reactive chemicals [2]. Upon sensing a damaging stimulus, action potentials are transmitted to nociceptor cell bodies in the dorsal root ganglia (DRG), which receive input from peripheral tissues such as the skin. Related sensory neurons in the vagal ganglia receive input from internal organs such as the heart, gut, and lungs. DRG signals are sent to the spinal cord to be perceived as pain, while vagal signals are sent to the brain stem and mediate nausea, cough, and other protective reflexes. Nociceptors, like immune cells, play an active role in host–pathogen defense. Nociceptors express receptors including Toll-like receptors (TLRs) and formyl peptide receptors (FPRs) that can directly sense microbes. Furthermore, nociceptors release neuropeptides that potently signal to immune cells. We review recent studies that highlight how microbes interact with nociceptors during infection to modulate pain and cough.