Chronic pain is one of the major medical challenges of our time, with many patients receiving unsatisfactory relief from the currently available drugs. Despite that chronic pain is one of the most common reasons for seeking medical care, most of the common chronic pain disorders remain unexplained at the cellular and molecular level. We have made the paradigm-shifting discovery that the common and challenging chronic pain condition fibromyalgia, is caused by autoantibodies. In an effort to identify potential drug targets, we used RNA sequencing of sensory ganglia from mice treated with patient antibodies. This PhD studentship will be focused on identified target candidates playing a role in sensory neurons excitability.
The first 12-18 months will be focused on in vitro studies in cell lines expressing target candidates. The student will use fluorescent indicators to monitor membrane potential and intracellular Ca2+ and patch-clamp electrophysiology to analyse current responses in cell lines, and primary sensory neurons isolated from mice. Studies of cell lines will primarily be focused on the characterisation of novel pharmacological tools, whereas studies of sensory neurons will determine the impact of the modulation of target candidates on excitability.
During years 2-3, the student will start to examine the role of targets modulating neuronal excitability in chronic pain models, particularly widespread musculoskeletal pain models. These studies will include analysis of expression levels, functional (patch-clamp and imaging) studies of primary neurons, and behavioural studies in vivo. Key cellular findings will be validated in sensory neurons derived from human induced pluripotent stem cells.
In parallel, immunohistochemistry, in situ hybridization and transcriptomic analysis will be used to identify cells and molecules involved. The student will present findings at national and international meetings and to rheumatology patients who live with chronic widespread pain. Year 4 will be focused on writing manuscripts, thesis, and applications.
Sensory neuron hyperexcitability as a cause of chronic pain
Representative Publications
Passive transfer of fibromyalgia symptoms from patients to mice Goebel, A., Krock, E., Gentry, C., Israel, M. R., Jurczak, A., Morado Urbina, C., Sandor, K., Vastani, N., Maurer, M., Cuhadar, U., Sensi, S., Nomura, Y., Menezes, J., Baharpoor, A., Brieskorn, L., Sandström, A., Tour, J., Kadetoff, D., Haglund, L., Kosek, E., Bevan, S., Svensson, C. I. & Andersson, D. A., 1 Jul 2021, In: The Journal of clinical investigation. 131, 13, e144201. DOI: https://doi.org/10.1172/JCI144201
Autoantibodies produce pain in Complex Regional Pain Syndrome by sensitizing nociceptors Cuhadar, U., Gentry, C., Vastani, N., Sensi, S., Bevan, S., Goebel, A. & Andersson, D., 1 Dec 2019, In: Pain. 160, 12, p. 2855-2865. DOI: 10.1097/j.pain.0000000000001662
Impaired Nociception in the Diabetic Ins2+/Akita Mouse Vastani, N., Guenther, F., Gentry, C., Austin, A. L. F., King, A., Bevan, S. & Andersson, D. A., 1 Aug 2018, In: Diabetes. 67, 8, db171306. DOI: 10.2337/db17-1306
Photoactivation of olfactory sensory neurons does not affect action potential conduction in individual trigeminal sensory axons innervating the rodent nasal cavity. Maurer M, Papotto N, Sertel-Nakajima J, Schueler M, De Col R, Möhrlen F, Messlinger K, Frings S, Carr RW. 14 Aug 2019, In: PLoS One. 14, 8, e0211175.
Passive transfer of fibromyalgia symptoms from patients to mice Goebel, A., Krock, E., Gentry, C., Israel, M. R., Jurczak, A., Morado Urbina, C., Sandor, K., Vastani, N., Maurer, M., Cuhadar, U., Sensi, S., Nomura, Y., Menezes, J., Baharpoor, A., Brieskorn, L., Sandström, A., Tour, J., Kadetoff, D., Haglund, L., Kosek, E., Bevan, S., Svensson, C. I. & Andersson, D. A., 1 Jul 2021, In: The Journal of clinical investigation. 131, 13, e144201