Online Ph.D Defence by Line Bay Sørensen
Line Bay Sørensen will defend her PhD thesis: "Nerve Growth Factor (NGF) induced muscle hyperalgesia and evoked pain in healthy humans"
30.04.2020 kl. 13.00 - 16.00
13.00 Opening by the Moderator
13.05 PhD lecture by Line Bay Sørensen
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
Due to the current circumstances the Ph.D defence will take place online via Skype for Business. If you wish to attend, please send an email to Kristine Uldal Knudsen before 28. april 2020 at 12:00.
The Faculty Council has appointed the following adjudication committee to evaluate the thesis and the associated lecture:
Associate Professor Anne Marie Heegaard
University of Copenhagen
Professor Martin Schmelz
Associate Professor Steffen Frahm
Professor Pascal Madeleine
Chronic muscle pain affects a large proportion of the adult population. In patients with muscle pain, increased sensitivity of deep tissue structures is a major complaint that over time becomes more painful and interferes with daily activities. Both peripheral and centrally mediated pain mechanisms have been suggested to play important roles in generating altered pain processing, although less clear is their contribution to maintenance of long-term symptoms such as muscle hyperalgesia and evoked pain. One of the greatest challenges, however, in treating these conditions is the present lack of successful management of pain, possibly due to an inadequate understanding of muscle pain pathology and the involved mechanisms in pain signaling pathways.
Pain research has advanced through the development of various translational models in which pain can be evoked in a standardized and reproducible manner. Different methods are utilized for the induction of experimental muscle pain; however, only few can produce long-lasting symptoms that are able to mimic clinical pain characteristics. Evidence from clinical and experimental studies suggest that the neurotrophic factor, Nerve Growth Factor (NGF) is a key mediator of nociception and is involved in various pain states. Studies have examined NGF’s sensitizing effects on both peripheral and central mechanisms, and demonstrated profound hyperalgesic effects after NGF administration in tissues. Pain responses in NGF models are still controversial, and the mechanisms affecting NGF-induced muscle pain sensitivity are poorly understood and have not been clearly demonstrated in humans. Therefore, the aim of this PhD-project was to explore evoked and non-evoked pain responses, and the effects of NGF administration on pain sensitivity using methods assessing both peripheral and central mechanisms, in healthy human NGF pain models.
The first study showed that five injections of low-dose NGF spatially distributed into the tibialis anterior muscle induced pronounced muscle hyperalgesia, functional pain and increased contraction-evoked pain with larger pain areas as compared with a single-site bolus injection of NGF of the same total dose. The second study demonstrated that an acute provoked acidification of the muscle environment (i.e. ischemic muscle contractions) did not facilitate muscle pain sensitivity, but NGF may sensitize muscle nociceptors possibly through the responsiveness of chemo-sensitive channels as higher contraction pain was evoked with the NGF injected muscle during ischemia as compared to a non-sensitized muscle. In the third study, subjects sensitized by three low-dose NGF injections separated by 2-day intervals induced prolonged functional pain but the intensity was less severe. Additionally, ischemic contraction-evoked pain was increased with prolonged NGF sensitization. However, maintained NGF-induced sensitization did not significantly affect central mechanisms, as assessed by temporal summation of pain and conditioned pain modulation.
Taken together, the current PhD studies have clarified significant details of the NGF pain model, which is an important step forward and offers advantages for future studies of prolonged muscle pain and muscle hyperalgesia. The current findings illustrate that NGF plays a role in sensitizing peripheral afferents over a large area of the muscle, producing more widespread pain areas and altered responses during ischemic conditions. Hence, these newly-developed NGF models may better mimic some aspects of clinical muscle pain and peripheral muscle sensitization with ischemic complicity.
CNAP - Center for Neuroplasticity and Pain, Department of Health Science and Technology, Aalborg University
Skype for Business
28.04.2020 kl. 12.00