Neuroinflammatory Pathways Associated with Chronic Post-Thoracotomy Pain: A Review of Current Literature

Chronic post-thoracotomy pain (CPTP) is a major clinical problem that affects up to 35-55% of patients undergoing thoracic incisions. Evidence suggests that multiple cellular signaling pathways and neuro-inflammatory mediators may play an essential role in the pathogenesis of CPTP. In this comprehensive review, we present the current evidence on the cellular signaling pathways and inflammatory changes associated with the initiation and maintenance of CPTP, focusing on the potential application of these findings in the clinical setting. An electronic search of Medline, EMBASE, Cochrane, Google Scholar, and ClinicalTrials.gov was performed, and 3652 abstracts were identified. After an initial abstract screening, 131 studies underwent a full-text review, and nine papers were eventually included in this review. Studies were included if they assessed the cellular signaling pathways or inflammatory processes associated with the induction and/or maintenance of CPTP. All the identified studies were pre-clinical studies conducted on animal models. Our search identified seven cellular pathways (NK-1 receptor (NK-1), Glutaminase 1, Toll-like receptor 4 (TLR4), Resolvins, Ror-2, Sonic hedgehog signaling (Shh), and Wnt5a/Wnts) and six cytokines (IL-1β, IL-6, IL-8, IL-10, IFN-γ, and TNF-α) that were investigated in the context of CPTP. Multiple cellular signaling pathways and inflammatory cytokines may play an important role in the neuroinflammatory changes associated with the induction and maintenance of chronic post-thoracotomy pain in animal models. However, the clinical impact and therapeutic utility of these neuroinflammatory changes in routine clinical practice have yet to be demonstrated.