The neuroimmune axis and chronic pain disorders

Both the nervous system and the immune system alert and protect the body against pathogen invasion and damage, but the extent of their interactions have only truly been elaborated in the past few decades. Lymph nodes (LN) are essential immune command centers that modulate the adaptive immune response through the integration of a multitude of signals and activation of T and B lymphocytes. LN are also known to be innervated by sympathetic and sensory nerves. While sympathetic regulation of the immune system is well-established, the impact of sensory neurons has been overlooked. Recently, the sensory neuronal population that innervates popliteal LN has been described in detail, with most cells characterized as peptidergic nociceptors. Of further interest, patients suffering with pain disorders like fibromyalgia, complex regional pain syndrome (CRPS) and hereditary sensory and autonomic neuropathies (HSAN) display both immune and autonomic dysfunction. The localization of nociceptors on LN indicates that there may be a larger impact of sensory neuronal signaling on adaptive immunity than has been explored currently. Therefore, this paper investigates the impact of neural signaling on immunity, specifically the LN and its main cell populations, and aims to address the gaps in our understanding of immune problems featured in pain disorders with aberrant or absent pain.