Mediators, Receptors, and Signalling Pathways in the Anti-Inflammatory and Antihyperalgesic Effects of Acupuncture

Figure 1

Proposed model for the complex cross talk between various receptors and mediators in early phase response in allergic rhinitis. 1: nerve growth factor (NGF) activates tyrosine kinase A (TrkA) receptor which in turn increases production and release of substance P (SP). Activation of TrkA receptor also initiates signalling via the PI3K/PIP3 pathway to increase expression and sensitivity of transient receptor potential vallinoid (TRPV1) receptor. 2: chemokine receptors (CCR2, CCR3, and CXCR8) sensitize TRPV1 receptor via a PLCβ/PKC pathway. 3: TRPV1 receptor increases production and release of proinflammatory neuropeptides SP and CGRP which act synergistically to promote degranulation of primed mast cells. Histamine released by mast cells activates histamine 1 receptor (H1R) producing signalling via the phospholipase A₂/lipoxygenase pathway to activate TRPV1, triggering early phase allergic inflammatory response. 4: chemokine receptors are heterologously desensitized by both adenosine (A2a) receptors and opioid receptors (MOR, DOR, and KOR). 5: Substance P is inhibited by met-enkephalin via Mu opioid receptors (MOR). A2a: adenosine 2a receptor, CCR2, CCR3: CC chemokine receptors 2 & 3, CXCR8: CXC chemokine receptor 8, PLCβ: phospholipase C β, PKC: protein kinase C, NGF: nerve growth factor, TRPV1: transient receptor potential vallinoid 1, TrkA: tyrosine kinase A receptor, H1R: histamine 1 receptor, SP: substance P, CGRP: calcitonin gene-related peptide, PI3K/PIP3: phosphatidylinositol 3 kinase/phosphatidylinositol phosphate 3 pathway, PLA₂/LO: phospholipase A₂/lipoxygenase pathway, MOR: Mu opioid receptor, DOR: delta opioid receptor, KOR: kappa opioid receptor, and MEK: met-enkephalin.