Clinical Implications of Basic Science Discoveries: Nociceptive Neurons as Targets to Control Immunity—Potential Relevance for Transplantation

Abstract

Increasing evidence indicates the existence of a complex cross-regulation between the most important biosensors of the human body: The immune and nervous systems. Cytokines control body temperature and trigger autoimmune disorders in the central nervous system, whereas neuropeptides released in peripheral tissues and lymphoid organs modulate inflammatory (innate) and adaptive immune responses. Surprisingly, the effects of nerve fibers and the antidromic release of its pro-inflammatory neuropeptides on the leukocytes of the immune system that mediate graft rejection are practically unknown. In the transplantation field, such area of research remains practically unexplored. A recent study by Riol-Blanco et al has revealed new details on how nociceptive nerves regulate the proinflammatory function of leukocytes in peripheral tissues. Although the mechanism(s) by which neuroinflammation affects the immune response against the allograft remains unknown, recent data suggest that this new area of research is worth exploring for potential development of novel complementary therapies for prevention/treatment of graft rejection.

Immunobiology in VCA

“…Data from our own center as well as others have suggested that surgery, burns, and physical trauma can trigger acute rejection episodes . The authors suggest that depletion of sensory nerve fibers may be a new treatment alternative to control rejection . While that would not be an appropriate treatment for hand or face VCA recipients, these studies have significant implications in understanding how trauma and environmental influences can trigger rejection in VCA recipients.…”

“…Larregina et al . noted that neuropeptides released in peripheral tissues modulate both innate and adaptive immune responses. The sensory function of surface tissues such as the skin depends on innervation provided by sensory Aδ and C nerve fibers.…”

“…After these receptors are activated, the brain perceives sensations of itch or pain, and by antidromic reflex pro‐inflammatory neuropeptides are secreted in the affected tissues. This occurs especially in type I and type 2 hypersensitivity reactions . Graft rejection is mediated primarily by type 1 hypersensitivity.…”