Periodic Reporting for period 2 - FRESCOatCNAP (FrontierResearchCompentences@CNAP)
Période du rapport: 2019-04-01 au 2022-03-31
Chronic pain is a key societal challenge affecting one out of five adults. It is generally poorly treated, leading to high personal and societal burden. The healthcare costs and loss in productivity associated with chronic pain in European countries are estimated to be a significant proportion of gross domestic products. Despite extensive research into pain mechanisms, we still do not know why acute pain develops into chronic pain, how this transition takes place, and what provokes the development. The long-term perspective of the research conducted within the FrontierRESearchCOmpetences@CNAP (FRESCO@CNAP) programme is to inform and train the next generation of researchers within pain mechanisms and management techniques, thereby helping to reduce the burden of chronic pain both on a personal and a societal level.
Apart from the scientific goals, the main objectives of the FRESCO@CNAP programme were to provide Early-Stage Researchers (ESRs) with world-class training in both scientific and transferrable skills, and to promote internationalisation and mobility of researchers. The eight ESRs were recruited from around the world to the Center for Neuroplasticity and Pain (CNAP), Department of Health Science and Technology, Aalborg University, Denmark. CNAP is a Centre of Excellence funded by the Danish National Research Foundation with the purpose of conducting frontline research on novel tools for identifying and modulating key features of human pain mechanisms. It is thus the ideal research environment for new insights and scientific discoveries in the field of pain management. Further objectives of the programme were to guarantee a fair, transparent, merit-based, impartial, supportive, and equitable recruitment procedure; and to give the ESRs interdisciplinary, international, and inter-sectoral experience.
Apart from the scientific goals, the main objectives of the FRESCO@CNAP programme were to provide Early-Stage Researchers (ESRs) with world-class training in both scientific and transferrable skills, and to promote internationalisation and mobility of researchers. The eight ESRs were recruited from around the world to the Center for Neuroplasticity and Pain (CNAP), Department of Health Science and Technology, Aalborg University, Denmark. CNAP is a Centre of Excellence funded by the Danish National Research Foundation with the purpose of conducting frontline research on novel tools for identifying and modulating key features of human pain mechanisms. It is thus the ideal research environment for new insights and scientific discoveries in the field of pain management. Further objectives of the programme were to guarantee a fair, transparent, merit-based, impartial, supportive, and equitable recruitment procedure; and to give the ESRs interdisciplinary, international, and inter-sectoral experience.
During the first period of FRESCO@CNAP the recruitment of the ESRs took place, with positions being announced internationally resulting in a large cohort of qualified applicants, and evaluations carried out by international independent reviewers. The recruitment process resulted in the selection of eight highly talented ESRs from around the world (six different nationalities, none of them from Denmark), thus strengthening the internationalisation at CNAP.
By the end of the reporting period of FRESCO@CNAP, the ESRs are on the way to complete their high-quality training programme, consisting of the programme offered by the Doctoral School of the Faculty of Medicine at Aalborg University, complemented by specific, targeted workshops; for instance on entrepreneurship, and the dedicated FRESCO@CNAP workshop in May 2021, which combined scientific presentations with presentations on career options and transferrable skills. The ESRs have furthermore been exposed to interdisciplinary, international and intersectoral environments, through collaboration with organisations (both academic and non-academic, both in Denmark and abroad), collaboration across disciplinary groups in CNAP (e.g. in the quarterly roundtable meetings), and through international research visits and conference presentations – although the corona pandemic meant that some research visits had to be cancelled, rescheduled or redesigned, and that many international academic conferences were postponed or moved online. Despite delays due to the pandemic, five ESRs have so far successfully defended their PhDs by the end of June 2022.
Persistent pain after a tissue injury has healed may be partly caused by maladaptive pain neuroplasticity, i.e. by undesirable adaptations of the central nervous system to changes within the body. CNAP does frontline fundamental research to identify novel tools to study the dynamics of pain neuroplasticity. In collaboration with their supervisors, the ESRs designed and executed scientific studies that have advanced the state-of-the-art knowledge in the field of pain and neuroplasticity. Two ESR projects have uniquely studied changes in brain measures when extending from short-lasting to long-lasting pain models (24 hours or days) in healthy subjects. For instance, the corticomotor and somatosensory excitability was reduced due to prolonged pain as well as dampened communication between selected brain regions. Some of these effects did not reverse immediately if the pain was diminished after 1 day with pain, suggesting that such brain mechanisms are slowly adaptive. These novel findings illustrate potential neuroplastic mechanisms that may be involved in the initial transition from acute to prolonged pain in patients. Subsequently, non-invasive low-intensity brain stimulation techniques were added to the pain models, demonstrating that the pain-induced excitability changes in the brain could be reversed and illustrating a potential for further studies using brain stimulation techniques to counteract pain mechanisms in prolonged pain conditions. Other ESR projects studied the effects of peripheral transcutaneous electrical stimulation on pain perception as well as the corticomotor and somatosensory excitability changes and connectivity between brain regions. Alternative ways of changing the brain processing can be by illusory movements (not performing the movement), and one ESR studied how this related to a decrease of pain sensation. It is well known that parts of the pain processing take place in the spinal cord and can be studied by the nociceptive withdrawal reflex – this was further studied in an ESR project with particular focus on how cognitive modulation (brain) can affect such spinal effects. Understanding more details of pain mechanisms detected in human studies requires translational animal studies. The pig brain is physiologically very similar to the human brain, and pig pain models are therefore an important and novel way to study fundamental pain mechanisms. Two ESRs have contributed significantly to developing and conducting studies on direct brain recordings in pigs combined with pain models. This is a highly novel way of translating the human findings to fundamental pain mechanisms.
The results of the programme have been disseminated widely, through peer-reviewed publications in high-impact journals (with further manuscripts in preparation), through oral/poster presentations at some of the key international conferences on pain (whether in-person or online), and via social media. The novel scientific findings have been important for setting the future research agenda within pain mechanisms and neuroplasticity as well as securing further funding to study such mechanisms. Understanding key pain mechanisms in the transition from short-term to long-term pain may in the long perspective be exploited to improve the future pain management, thus helping millions of pain patients.
By the end of the reporting period of FRESCO@CNAP, the ESRs are on the way to complete their high-quality training programme, consisting of the programme offered by the Doctoral School of the Faculty of Medicine at Aalborg University, complemented by specific, targeted workshops; for instance on entrepreneurship, and the dedicated FRESCO@CNAP workshop in May 2021, which combined scientific presentations with presentations on career options and transferrable skills. The ESRs have furthermore been exposed to interdisciplinary, international and intersectoral environments, through collaboration with organisations (both academic and non-academic, both in Denmark and abroad), collaboration across disciplinary groups in CNAP (e.g. in the quarterly roundtable meetings), and through international research visits and conference presentations – although the corona pandemic meant that some research visits had to be cancelled, rescheduled or redesigned, and that many international academic conferences were postponed or moved online. Despite delays due to the pandemic, five ESRs have so far successfully defended their PhDs by the end of June 2022.
Persistent pain after a tissue injury has healed may be partly caused by maladaptive pain neuroplasticity, i.e. by undesirable adaptations of the central nervous system to changes within the body. CNAP does frontline fundamental research to identify novel tools to study the dynamics of pain neuroplasticity. In collaboration with their supervisors, the ESRs designed and executed scientific studies that have advanced the state-of-the-art knowledge in the field of pain and neuroplasticity. Two ESR projects have uniquely studied changes in brain measures when extending from short-lasting to long-lasting pain models (24 hours or days) in healthy subjects. For instance, the corticomotor and somatosensory excitability was reduced due to prolonged pain as well as dampened communication between selected brain regions. Some of these effects did not reverse immediately if the pain was diminished after 1 day with pain, suggesting that such brain mechanisms are slowly adaptive. These novel findings illustrate potential neuroplastic mechanisms that may be involved in the initial transition from acute to prolonged pain in patients. Subsequently, non-invasive low-intensity brain stimulation techniques were added to the pain models, demonstrating that the pain-induced excitability changes in the brain could be reversed and illustrating a potential for further studies using brain stimulation techniques to counteract pain mechanisms in prolonged pain conditions. Other ESR projects studied the effects of peripheral transcutaneous electrical stimulation on pain perception as well as the corticomotor and somatosensory excitability changes and connectivity between brain regions. Alternative ways of changing the brain processing can be by illusory movements (not performing the movement), and one ESR studied how this related to a decrease of pain sensation. It is well known that parts of the pain processing take place in the spinal cord and can be studied by the nociceptive withdrawal reflex – this was further studied in an ESR project with particular focus on how cognitive modulation (brain) can affect such spinal effects. Understanding more details of pain mechanisms detected in human studies requires translational animal studies. The pig brain is physiologically very similar to the human brain, and pig pain models are therefore an important and novel way to study fundamental pain mechanisms. Two ESRs have contributed significantly to developing and conducting studies on direct brain recordings in pigs combined with pain models. This is a highly novel way of translating the human findings to fundamental pain mechanisms.
The results of the programme have been disseminated widely, through peer-reviewed publications in high-impact journals (with further manuscripts in preparation), through oral/poster presentations at some of the key international conferences on pain (whether in-person or online), and via social media. The novel scientific findings have been important for setting the future research agenda within pain mechanisms and neuroplasticity as well as securing further funding to study such mechanisms. Understanding key pain mechanisms in the transition from short-term to long-term pain may in the long perspective be exploited to improve the future pain management, thus helping millions of pain patients.
The scientific impact of the project is clearly beyond the state of the art. Importantly, the main impact of the project has been on the ESRs’ training and career options. Indeed, five of the ESRs have already secured new positions, both in academic and industry settings (e.g. in pharmaceutical companies and medical device companies). Without doubt, installing the FRESCO@CNAP program has demonstrated robust and long-term effects for the eight ESRs and the research performed. Moreover, embedding FRESCO@CNAP in a Centre of Excellence has strengthened the focus on research training at large for all ESRs in CNAP which is recognised as a very important secondary outcome.