Peripheral Neuroinflammation and Pain: How Acute Pain Becomes
Chronic

Mark   A.   Schumacher
doi:10.2174/1570159X21666230808111908
Abstract

The number of individuals suffering from severe chronic pain and its social and financial impact is staggering. Without significant advances in our understanding of how acute pain becomes chronic, effective treatments will remain out of reach. This mini review will briefly summarize how critical signaling pathways initiated during the early phases of peripheral nervous system inflammation/ neuroinflammation establish long-term modifications of sensory neuronal function. Together with the recruitment of non-neuronal cellular elements, nociceptive transduction is transformed into a pathophysiologic state sustaining chronic peripheral sensitization and pain. Inflammatory mediators, such as nerve growth factor (NGF), can lower activation thresholds of sensory neurons through posttranslational modification of the pain-transducing ion channels transient-receptor potential TRPV1 and TRPA1. Performing a dual role, NGF also drives increased expression of TRPV1 in sensory neurons through the recruitment of transcription factor Sp4. More broadly, Sp4 appears to modulate a nociceptive transcriptome including TRPA1 and other genes encoding components of pain transduction. Together, these findings suggest a model where acute pain evoked by peripheral injury-induced inflammation becomes persistent through repeated cycles of TRP channel modification, Sp4-dependent overexpression of TRP channels and ongoing production of inflammatory mediators.
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Graphical Abstract

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DOI https://dx.doi.org/10.2174/1570159X21666230808111908	Print ISSN 1570-159X
Publisher Name Bentham Science Publisher	Online ISSN 1875-6190
Current Neuropharmacology

Peripheral Neuroinflammation and Pain: How Acute Pain Becomes Chronic

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