About this trial
Chronic Post-Surgical Pain (CPSP) is a condition that involves experiencing pain and/or discomfort that lasts for more than 3 months following surgery without any explainable cause of this pain such chronic infection or pain caused from a condition preceding surgery. This condition negatively impacts health related quality of life and is associated with significant financial burden both for the patient and health care system. Patients undergoing common surgeries such as amputation, breast surgery, hernia repair, coronary artery bypass, and caesarean section can be prone to developing CPSP. CPSP may be caused by the release and expression of different cellular molecules called cytokines and chemokines that can cause a pain response when they are present in the body at certain levels. After surgical incision, tissue cells have been shown to release cytokines and chemokines, thus increasing the concentration of these molecules in the patient's blood. It is not entirely known what mechanisms cause the increased expression of chemokines and cytokines. One method that may play a role in in this expression is epigenetics which is the alteration of gene expression without permanently altering the structure of DNA. Unlike mutations, epigenetic changes are dynamic, possibly reversible, and are influenced by environmental and behavioral changes such as diet, exercise, disease, stress, toxin exposure etc. Epigenetic changes occur all throughout our life and have been associated with several disease processes such as cancer, diabetic complications, and chronic pain. At the molecular level, certain events take place that can regulate (increase or decrease) the expression of cytokines and chemokines, most notably DNA methylation of their promotor (which involves adding molecules to DNA that does not change its structure but changes it's activity). The investigators are conducting this study to determine if the alteration of specific cytokines are associated with the occurrence of CPSP and whether these cytokines are regulated by DNA methylation at their promoter. This study will take place at London Health Sciences Centre and will recruit up to 60 patients who will be undergoing a thoracotomy procedure (surgery of the chest area).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
18 years of age or older
Undergoing unilateral thoracotomy for the first time on that side
Willing to provide informed consent for study participation.
Patient with malignancy that needs thoracotomy for surgical resection.
Disqualifiers
Chronic pain prior to surgery
Pre-existing fibromyalgia
Long-term opioid use
Diabetes mellitus
Trial population
Adult patients scheduled to undergo thoracotomy for malignancy at Victoria Hospital, London Health Science Centre.
Trial design
Cohort
Prospective
Treatments tested in this trial
Unilateral thoracotomy
Other interventionUnilateral thoracotomy to proceed as per standard of care guidelines. Thoracic epidural analgesia, or patient controlled analgesia (PCA) pumps will be offered to each study participant as per standard of care. Pre- and post-operative (post-operative day 1 and 3 months) pain scores and blood samples will be collected. Blood samples will be analyzed to determine the concentration of cytokines, chemokines, and growth factors that are potentially associated with CPSP (epidermal growth factor, eotaxin, fibroblast growth factor basic, G-CSF, GM-CSF, human growth factor, IFN-α, IFN-γ, IL-1ra, IL-1β, IL-2, IL-2r, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p40/p70), IL-13, IL-15, IL-17, IP-10, MCP-1, MIG, MIP-1α, MIP-1β, RANTES, TNF-α, and VEGF). DNA promotor methylation for these targets will also be investigated.
Treatment groups
Trial outcomes
Primary outcomes
Identification of temporal alterations of cytokines in patients with CPSP.
Cellular assays will be performed on blood samples obtained pre-and postoperatively to determined the level of expression of certain chemokines, cytokines, and growth factors that have been shown to be potentially related to CPSP. Pre and postoperative results will be compared to determine the association that each may have on the development of CPSP.
Identification of specific DNA promoter methylation regulating production of specific cytokines
Cellular assays will be performed on blood samples obtained pre-and postoperatively to determine if DNA promotor methylation is associated with changes in expression of the cytokines being investigated. Pre and postoperative results will be compared to determine the impact that this potential epigenetic change (DNA promotor methylation) may have on the development of CPSP.
Generate initial data to determine the sample size needed to adequately power a larger trial
As this is a pilot study, data will be analyzed to determine the sample size needed to power a larger, randomized controlled trial.
Locations
Sponsors and contacts
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