Chemokines and Pain in the Trigeminal System

Abstract

Chemotactic cytokines or chemokines are a large family of secreted proteins able to induce chemotaxis. Chemokines are categorized according to their primary amino acid sequence, and in particular their cysteine residues that form disulphide bonds to maintain the structure: CC, CXC, CX3C, and XC, in which X represents variable amino acids. Among their many roles, chemokines are known to be key players in pain modulation in the peripheral and central nervous systems. Thus, they are promising candidates for novel therapeutics that could replace current, often ineffective treatments. The spinal and trigeminal systems are intrinsically different beyond their anatomical location, and it has been suggested that there are also differences in their sensory mechanisms. Hence, understanding the different mechanisms involved in pain modulation for each system could aid in developing appropriate pharmacological alternatives. Here, we aim to describe the current landscape of chemokines that have been studied specifically with regard to trigeminal pain. Searching PubMed and Google Scholar, we identified 30 reports describing chemokines in animal models of trigeminal pain, and 15 reports describing chemokines involved in human pain associated with the trigeminal system. This review highlights the chemokines studied to date at different levels of the trigeminal system, their cellular localization and, where available, their role in a variety of animal pain models.

Sex-dependent Differences in the Genomic Profile of Lingual Sensory Neurons in Naïve and Tongue-Tumor Bearing Mice

“…Noteworthy femaleselective BPs including cytokine/chemokine production and signaling as well as angiogenesis. The contribution of various cytokine/chemokines in nociception and inflammation (103)(104)(105) is widely established and our data showed that the number of cytokine/chemokines altered in female neurons was higher than in males (i.e. 14 in females versus 3 in males).…”

Fifty years of development of neuroscientific insights into oro‐facial pain and its control

“…The TG neurons synthesise chemicals that are conveyed along their axons and released at their peripheral tissue endings and at their central presynaptic axon terminals. 20,86,88,89,107,108 The application of approaches such as those using patch-clamp recording, immunohistochemical and molecular biological methods developed or refined over this period has proven especially valuable. The use of these approaches has led to the identification of these particular chemicals as well as chemicals present in oro-facial tissues innervated by the afferents, the receptors for these chemicals and the influences of these chemical mediators on the excitability of the small-diameter (A-delta; C-fibre) nociceptive afferents.…”

“…While these afferents commonly contain chemicals such as glutamate and ATP, it has been found that they may vary in their content of neuropeptides such as substance P and CGRP; some nociceptive afferents may be peptidergic and others non-peptidergic (for review, see Refs. [20,35,68,87,88,108]). By the early 2000s, experimental studies in humans as well as animal models had identified several chemicals that can be released from cells and blood vessels in peripheral tissues as a result of noxious stimuli (e.g.…”

“…The TRP channel subtype vanilloid 1 (TRPV1) for instance can be activated by noxious heat (as well as by capsaicin), the subtype melastatin 8 (TRPM8) and subtype ankyrin 1 (TRPA1) by cold, and some other TRP channels by mechanical stimuli (for review, see Refs. [20,35,68,87,88,103,108]). The PIEZO receptor is another example of a receptor responding to mechanical stimuli.…”

Pathophysiology of Post-Traumatic Trigeminal Neuropathic Pain

“…Chemokine are key players in pain modulation in the peripheral and central nervous systems [ 52 ]. Their role in trigeminal pain and their pivotal role in PTNP development has been reviewed recently elsewhere [ 53 ]. CCL2 is a proinflammatory chemokine that recruits monocytes, memory T cells and dendritic cells to the site of inflammation [ 54 ] that is also known to be a glial cells mediator [ 55 ].…”