Crosstalk between the nociceptive and immune systems in host defence and disease

Abstract

Nociceptors and immune cells both protect the host from potential threats to homeostasis. There is growing evidence for bidirectional signalling between these two systems, and the underlying mechanisms are beginning to be elucidated. An understanding is emerging of how both the adaptive and innate immune systems can activate and sensitize nociceptors, and, reciprocally, how nociceptors modulate immune cells. In this Review, we discuss how these interactions can be adaptive and useful to the organism but also consider when such signalling might be maladaptive and pathophysiological, contributing to immune-mediated diseases and persistent pain states.

Early molecular correlates of adverse events following yellow fever vaccination

“…As expected, the pathways associated with both MSK and CNS AEs were PRRs, cytokines, and inflammatory signaling processes ( Figure 4C and Supplemental Table 5). These findings suggest that innate immune, cytokine, and inflammatory responses modulate nociceptive pathways and thus contribute to hyperalgesia (19,20).…”

Autoantibodies and pain

“…This results from neuronal sensitisation either at the level of the sensory neuron or within the CNS. It is now accepted that the immune system plays a crucial role in this process [5,6]. For example, immune-related factors such as cytokines and chemokines released by inflammatory cells in response to tissue injury or disease can directly sensitise nociceptors [7].…”

Muscle IL1 Drives Ischemic Myalgia via ASIC3-Mediated Sensory Neuron Sensitization

“…Blood flow alterations simultaneously induce afferent sensitization and lead to inflammation, which could be further sensitizing already vulnerable afferents, altogether resulting in a persistent pain state (McMahon et al, 2015). This suggests that therapeutic interventions targeting the endogenous inflammatory reaction to ischemia/reperfusion injury (IL1␤/IL1r1), rather than direct inhibition of channels that mediate altered mechanosensitivity and chemosensitivity (ASIC3), would be effective in subjects with I/R-based myalgia.…”

“…Blocking IL1␤ prevents inflammation-induced hypersensitivity, whether provoked by carrageenan or systemic administration of exogenous IL1␤ (Ferreira et al, 1988), and IL1r1 antagonists that are used to treat rheumatoid arthritis-related inflammation have also been shown to reduce pain (Hallegua and Weisman, 2002). IL1␤ is a known modulator of gene expression through numerous pathways (McMahon et al, 2015;O'Neill and Greene, 1998) and, in PenIL1r1 ϩ I/R animals, both IL1r1 and ASIC3 upregulation were inhibited after I/R (Figs. 1, 7), suggesting that ASIC3 is downstream of IL1␤/IL1r1.…”