13.00 Opening by the Moderator Lars Arendt-Nielsen
13.05 PhD lecture by Rocco Giordano
14.00 Questions and comments from the Committee
Questions and comments from the audience at the Moderator’s discretion
16.00 Conclusion of the session by the Moderator
The Faculty Council has appointed the following adjudication committee to evaluate the thesis and the associated lecture:
Bijar Ghafouri, Associate Professor, PhD, Linköbing University, Sweden
Paola Sacerdote, Professor, PhD, Università degli Studi de Milano, Italy
Tue Bjerg Bennike, Associate Professor, Department of Health Science and Technology, Aalborg University, Denmark
Lars Arendt-Nielsen, Professor, Department of Health Science and Technology, Aalborg University, Denmark
Osteoarthritis (OA) is the most frequent painful musculoskeletal diagnosis in the older population and the most prominent cause of disability. Total knee replacement (TKR) is expected to provide pain relief for patients with severe OA, however, around 20% of knee OA (KOA) patients will experience chronic post-operative pain after TKR surgery. Several studies have found high preoperative pain intensities and sensitization of central pain pathways as predictors for chronic post-operative pain following TKR. Recently a study found preoperative proinflammatory cytokines to be associated with chronic post-operative pain following TKR. Preclinical data shows that proinflammatory cytokines sensitize the peripheral nerve endings, which may eventually lead to central sensitization, indicating that preoperative increase levels of inflammatory markers could act as prognostic biomarkers for chronic post-operative pain following TKR. It is now apparent that epigenetic modifications, like the actions of noncoding RNAs (e.g. microRNAs, lncRNAs, siRNAs, circRNAs), may confer susceptibility to OA, which could open up new avenues for alternative therapeutic approaches. Several studies have illustrated the possible diagnostic potential of circulating non-coding RNAs in OA, indicating that this family of molecules may act as potential predictors for the development and progression of knee and hip osteoarthritis.
Real-time poly-chain reaction (RT-qPCR), quantitative and qualitative techniques allowed the evaluation of the circulating ncRNAs in serum samples, trough the isolation and retro-transcription of total RNAs. This methodology reduces non-specific results and reduces the difficult handling of the big amount of data obtained through other molecular biology techniques. Furthermore, a new proteomic approach, i.e. the proximity extension assay (PEA), has been used which gives a specific and standardized overview of inflammatory markers involved in the pathology.
This PhD-project includes three original studies that focus on the transcriptional, post-transcriptional and translation processes in the serum of patients with osteoarthritis, investigating factors that modulate the perception of pain.
The first study aimed to investigate the preoperative association of long non-coding RNAs (lncRNAs) and chronic post-operative pain, showing that patients with pain 1-year after surgery exhibited down-expression of three lncRNAs preoperatively when compared with patients with post-surgical full recovery.
The second study evaluated preoperative microRNA’s (miRNA’s) profile as potential predictive biomarkers for post-operative pain. Twenty-one miRNAs were analyzed, and three miRNAs showed a pre-operative differential level of expression in patients with low pain relief after surgery compared to patients with high pain relief. The miRNAs dysregulated showed a predictive value for the pain relief after surgery pointing to possible use for these miRNAs as potential biomarkers for post-operative pain.
The third study aimed to evaluate the preoperative serum expression of a panel of 92 inflammatory cytokines and highlight correlation with pain intensity in patients with KOA. Patients with KOA showed ten cytokines with significantly lowered expression in the serum and five cytokines with higher expression levels when compared to healthy participants. Specifically, FGF-21 and 4E-BP1 were associated with pain in KOA, and TWEAK, FGF-21, CSF-1, IL6 were identified as independent predictors for pain intensity.
In conclusion, the current Ph.d. thesis provides the first evidence of the interaction between post-transcriptional modifications and post-operative pain, which is an important step forward and offers advantages for future exploration of the involvement of epigenetic modifications in the pain field.
Aalborg University – Room 4-117, Niels Jernes Vej 14, Aalborg East.
15.09.2021 at 12.00