Chemokines as pain mediators and modulators

Abstract

Purpose of review-Chemokines are central to the innate immune response following tissue damage, injury and some diseases. The function of chemokines in nervous system autoimmune diseases has been long recognized. There is also growing evidence that disease-associated of injuryinduced functional expression of chemokines/receptors in both neural and non-neural elements of the peripheral nervous system play crucial roles in the pathophysiology of chronic pain.Recent findings-Chemokine involvement in neuropathic pain processing has recently been established in animal models. Evidence of chemokine contribution to chronic pain includes the upregulation of monocyte chemoattractant protein-1 (MCP-1/CCL2) and its respective receptor, CCR2, in many subpopulations of sensory neurons. Activation of CCR2 by MCP-1 elicits membrane depolarization, trigger action potentials and sensitizes nociceptors via transactivation of transient receptor potential channels TRPA1 and TRPV1. Increased signaling by stromal-derived factor-1 (SDF-1/CXCL12) and its receptor, CXCR4, has been shown to contribute to chronic pain behavior. The use of specific chemokine receptor antagonists for CCR2 and CXCR4 successfully reverses nociceptive pain behavior.Summary-Our results suggest that specific chemokines/receptors are up-regulated by sensory neurons following peripheral nerve injury and appear to participate in neural signal processing leading to chronic pain states. Taken together, chemokines and their receptors are potential targets for development of novel therapeutics.

Upregulation of Chemokine CXCL12 in the Dorsal Root Ganglia and Spinal Cord Contributes to the Development and Maintenance of Neuropathic Pain Following Spared Nerve Injury in Rats

“…In the last decade, numerous studies have demonstrated that, in addition to their role in coordinating the immune response, chemokines have important functions in the nervous system [6]. For example, excitatory chemokine signaling has been implicated in the pathogenesis of chronic pain in several animal models [7]. Stromal cell-derived factor-1a (SDF-1a), now also named CXCL12, belongs to the CXC subfamily and is a ligand for the G-protein-coupled receptor CXCR4.…”

A sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma

“…Over the last decades, evidence has mounted for bi-directional feedback between immunogenic and neurogenic mechanisms in airway inflammation (6,7). Neuronal activation causes pain and irritation, neurogenic inflammation, mucus secretion, and reflex responses, such as cough, sneezing, and bronchoconstriction (8,9).…”

Expert Panel Consensus Recommendations for the Pharmacological Treatment of Acute Pain in the Middle East Region

“…4 Sensitization may occur peripherally (increased responsiveness of receptors) or centrally (increased responsiveness of secondary neurons in the central nervous system to stimuli that may even be subthreshold). 22,23 The cellular and neurochemical mechanisms underlying hyperalgesia and allodynia are complex and beyond the scope of the current article. The clinical implications of hyperalgesia and allodynia are important, since individuals who develop sensitization are at high risk of progressing from acute to chronic pain.…”

“…13 Acute pain, even of relatively short duration, activates secondary peripheral and central mechanisms that may result in hyperalgesia and allodynia. 22,23 Hyperalgesia is increased sensitivity to pain, and allodynia is a special case of hyperalgesia involving painful sensations caused by stimuli that do not normally elicit pain. 4 The physiological mechanism underlying both hyperalgesia and allodynia is sensitization, including a reduction in pain threshold and increased intensity of response to a previously painful stimulus.…”