TRPV1 and SP: key elements for sepsis outcome?

Abstract

Sensory neurons play important roles in many disorders, including inflammatory diseases, such as sepsis. Sepsis is a potentially lethal systemic inflammatory reaction to a local bacterial infection, affecting thousands of patients annually. Although associated with a high mortality rate, sepsis outcome depends on the severity of systemic inflammation, which can be directly influenced by several factors, including the immune response of the patient. Currently, there is a lack of effective drugs to treat sepsis, and thus there is a need to develop new drugs to improve sepsis outcome. Several mediators involved in the formation of sepsis have now been identified, but the mechanisms underlying the pathology remain poorly understood. The transient receptor potential vanilloid 1 (TRPV1) receptor and the neuropeptide substance P (SP) have recently been demonstrated as important targets for sepsis and are located on sensory neurones and non-neuronal cells. Herein, we highlight and review the importance of sensory neurones for the modulation of sepsis, with specific focus on recent findings relating to TRPV1 and SP, with their distinct abilities to alter the transition from local to systemic inflammation and also modify the overall sepsis outcome. We also emphasize the protective role of TRPV1 in this context.

Linked articles: This article is part of a themed section on Neuropeptides. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.170.issue-7.

Keywords: TRPV1; sensory neurones; sepsis; substance P.

Figure 1

Tachykinin gene encoding and receptor preference. The key tachykinins SP, NKA and NKB are encoded in TAC1 or TAC2 (rodent)/3 (human) genes, where different mRNA splice variants of PPT1 and PPT2 protein products can occur (α to γ). All tachykinins can bind to the three main NK receptors, but with different affinity for each, creating a situation of preferential agonists. NK receptors can signal independently, or their signalling can converge to become synergistic or antagonistic. This figure is adapted from that in Fernandes et al. (2009).