Cytokine and Chemokine Regulation of Sensory Neuron Function

Abstract

Pain normally subserves a vital role in the survival of the organism, prompting the avoidance of situations associated with tissue damage. However, the sensation of pain can become dissociated from its normal physiological role. In conditions of neuropathic pain, spontaneous or hypersensitive pain behavior occurs in the absence of the appropriate stimuli. Our incomplete understanding of the mechanisms underlying chronic pain hypersensitivity accounts for the general ineffectiveness of currently available options for the treatment of chronic pain syndromes. Despite its complex pathophysiological nature, it is clear that neuropathic pain is associated with short- and long-term changes in the excitability of sensory neurons in the dorsal root ganglia (DRG) as well as their central connections. Recent evidence suggests that the upregulated expression of inflammatory cytokines in association with tissue damage or infection triggers the observed hyperexcitability of pain sensory neurons. The actions of inflammatory cytokines synthesized by DRG neurons and associated glial cells, as well as by astrocytes and microglia in the spinal cord, can produce changes in the excitability of nociceptive sensory neurons. These changes include rapid alterations in the properties of ion channels expressed by these neurons, as well as longer-term changes resulting from new gene transcription. In this chapter we review the diverse changes produced by inflammatory cytokines in the behavior of sensory neurons in the context of chronic pain syndromes.

The effect of pain on cognitive function: A review of clinical and preclinical research

“…Recent research has highlighted the importance of glial cells in relation to pain (Inoue and Tsuda, 2009;McMahon et al, 2005;Miller et al, 2009), and in processes such as synaptic plasticity, important for learning and memory (Bains and Oliet, 2007). Furthermore, activated glial cells can release a variety of cytokines and neurotrophic factors which also modulate neural processes involved in pain and cognition (Covey et al, 2000;Ren and Dubner, 2008;Tanaka et al, 2006).…”

CCR2 chemokine receptor signaling mediates pain in experimental osteoarthritis

“…This has been specifically shown in nerve-injury models in rodents. In such models, chemokines and their receptors, particularly monocyte chemoattractant protein-1 (MCP-1 or CCL2) and its high-affinity receptor, chemokine (C-C motif) receptor 2 (CCR2), mediate excitatory effects at the level of both the DRG and the spinal cord (12,14).The importance of MCP-1/CCR2 signaling remains to be explored in animal models of complex disorders associated with chronic pain, such as osteoarthritis. Therefore, we decided to study the role of MCP-1/CCR2 in osteoarthritis pain using a surgical mouse model, induced by destabilization of the medial meniscus (DMM) (15).…”

“…This has been specifically shown in nerve-injury models in rodents. In such models, chemokines and their receptors, particularly monocyte chemoattractant protein-1 (MCP-1 or CCL2) and its high-affinity receptor, chemokine (C-C motif) receptor 2 (CCR2), mediate excitatory effects at the level of both the DRG and the spinal cord (12,14).…”

“…The development of pain behavior involves fundamental changes in the properties of neurons that signal pain, including alterations in gene transcription and protein expression in the sensory neurons of the dorsal root ganglia (DRG) (12,13). This has been specifically shown in nerve-injury models in rodents.…”

Acute spinal cord injury could cause activation of autophagy in dorsal root ganglia

“…2 These neurons have bipolar morphology, comprising an undifferentiated terminal with the synaptic terminal entering the dorsal horn of the spinal cord. 3 In the membrane of DRG neurons, many kinds of ion channels and receptors are expressed; these can change in response to nerve injury and can be involved in various physiological and pathological pathways.…”