Exploring the neurophysiological mechanisms and risk factors for the development of chronic postsurgical pain after thoracic surgery: Protocol for an observational feasibility study (Preprint)

BACKGROUND Chronic postsurgical pain (CPSP) is a debilitating chronic pain condition that particularly impacts patients undergoing thoracic surgery, with incidence rates of up to 50%. Current understanding of risk factors is limited, and pre-operative neurophysiological risk factors that may predict the development of CPSP have not been explored. Additionally, specific neural mechanisms underlying the transition to CPSP are not well characterized. As a novel approach, we propose to use transcranial magnetic stimulation (TMS) and electroencephalography (EEG), along with other patient and surgical factors to understand the neurophysiological mechanisms that underpin the onset of CPSP after thoracic surgery. OBJECTIVE The primary objective of this study is to evaluate the feasibility of our study design to inform a larger observational cohort study. Secondary objectives will include exploring pre-operative neurophysiological markers along with clinical characteristics to identify patients at a higher risk of developing CPSP, as well as exploring postoperative differences in cortical function between thoracic surgery patients who develop CPSP compared to those without CPSP. METHODS Thirty participants undergoing either video-assisted thoracic (VATS) or robotic-assisted thoracic (RATS) lobectomy, wedge resection, segmental section, or minimally invasive esophagectomy (MIE) will be recruited to take part in two assessment sessions. The first assessment will take place 2-3 weeks before surgery, and the second assessment will take place 3 months after surgery, where CPSP diagnosis of each participant will be assessed by the experimenter using a validated definition. Feasibility outcomes will include recruitment and retention rates of study participants. The secondary objectives will include evaluating predictors associated with the development of CPSP, as well as examining post-operative differences in neurophysiological measures between patients with and without CPSP. We will consider the following neurophysiological measures for these objectives: TMS measures of short-latency intracortical inhibition (SICI), cortical silence period (CSP), and motor evoked potentials (MEPs); EEG measures of resting band activity, event-related desynchronization (ERD), and corticomuscular coherence (CMC); Quantitative Sensory Testing of mechanical detection threshold (MDT) and pressure pain threshold (PPT). RESULTS This is an ethics approved ongoing study. Recruitment for the study began in January 2025. CONCLUSIONS This protocol details our study design for a feasibility study exploring the neurophysiological markers along with patient characteristics associated with the development of CPSP. Demonstration of feasibility is expected to lead to a larger study. Improved understanding of risk factors and mechanisms behind CPSP may inform the delivery of targeted therapies and preventive measures to reduce the incidence of CPSP after thoracic surgery.