Abstract
Chronic pain affects ~20% of the worldwide population. The clinical management of chronic pain is mostly palliative and results in limited success. Current treatments mostly target the symptoms or neuronal signaling of chronic pain. It has been increasingly recognized that glial cells, such as microglia, and inflammatory signaling play a major role in the pathogenesis of chronic pain. Caspases (CASPs) are a family of protease enzymes involved in apoptosis and inflammation. They are pivotal components in a variety of neurological diseases. However, little is known about the role of CASPs in microglial modulation as to chronic pain. In particular, our recent studies have shown that CASP6 regulates chronic pain via microglial inflammatory signaling. Inhibition of microglia and CASP signaling might provide a new strategy for the prevention and treatment of chronic pain.
Highlights
Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage
We summarize the major signaling pathways involved in microglial activation and chronic pain with an emphasis on caspases (CASPs)
Several lines of evidence suggest a unique role for this CASP in microglia activation and pain control: (1) CASP6 is highly expressed in the neuronal axons of primary sensory neurons that terminate in the superficial dorsal horn of the spinal cord [19, 65], (2) CASP6 is coexpressed with the calcitonin gene related peptide (CGRP), a wellknown peptide involved in inflammation and pain [66], (3) CASP6 surrounds microglial cell bodies and processes, and (4) CASP6 levels in the cerebrospinal fluid significantly increase after inflammation [19]
Summary
Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Mechanical or tactile allodynia is probably the most commonly observed symptom in inflammatory and neuropathic pain animal models. Current treatments of chronic pain include antidepressants, anticonvulsants, sodium channel blockers, NMDA antagonists, and opioids. These drugs only target neuronal pathways or symptoms and are limited by their. Microglial cells in chronic pain are a hot topic and fast growing area of research In such diverse and rapidly developing research, we cannot possibly cover all of the work that has been carried over the last two decades and we certainly expect additional progress will have been made by the time this review is published. Potential microglial mechanisms and therapeutic approaches for the modulation of CASP6 in chronic pain are described
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