Martin Freudensprung

Martin Freudensprung

Bachelor's Thesis

Observer-independent scratching and wiping detection for pruritus and pain assessment in mice

Advisors
Ivanna K. Timotius (M.Sc.), Dr. Dr. Andreas E. Kremer, Prof. Dr. Björn Eskofier

Duration
07/2018 – 12/2019

Abstract
“Chronic pruritus (itch) is a disabling symptom accompanying a broad range of systemic disorders such as chronic liver diseases, chronic renal failure, malignancies, infections, endocrine and hematologic diseases” [1]. Pruritus and pain are closely intertwined processes and various chemical substances may cause both, itch and pain sensation. To give an example, lysophosphatidic acid (LPA) is associated with pruritus in cholestatic patients but may also initiate neuropathic pain. Intradermally applied histamine causes itching, while subcutaneous injection is associated with pain. Important further substances involved in itch signaling mediated their effects via Mas-related G protein coupled receptors (MRG) [4][6]. To characterize endogenous algogens or pruritus as well as newly discovered pharmaceutically active compounds, it is necessary to distinguish itch and pain induction based on the behavior in mice. In mice, itching can be quantified based on scratching movements with their hind paws in response to pruritic stimuli applied to the nape of the neck or to the cheek. Whereas, facial wiping with the forelimb has widely been used as indicator of pain in the mouse [2][5].

In preclinical studies an objective way to distinguish and quantify pruritus from pain is warranted which respectively corresponds to detecting visually scratching and wiping behavior. Currently, an established method is available to detect automatically scratching behavior [1]. This method is based on small Teflon-coated magnets implanted in the hindpaws of mice placed in a coil-surrounded cage. The paw movements induce a measurable current [3]. To trigger pain and itch, the mouse skin is stimulated with capsaicin (pain) and histamine (itch), respectively.

The aim of this thesis is to develop an algorithm to separate and quantify both wiping and scratching behavior of mice based on data collected from magnet-implanted mice placed in a magnetic coil-surrounded cage. The method will be built based on signal processing approaches and basic machine learning algorithm.

References:

  1. Kremer, Andreas E.; Martens, Job J. W. W.; Kulik, Wim; Ruëff, Franziska; Kuiper, Edith M. M.; van Buuren, Henk R. et al. (2010): Lysophosphatidic acid is a potential mediator of cholestatic pruritus. In: Gastroenterology 139 (3), 1008-18, 1018.e1. DOI: 10.1053/j.gastro.2010.05.009.
  2. Shimada, Steven G.; LaMotte, Robert H. (2008): Behavioral differentiation between itch and pain in mouse. In: Pain 139 (3), S. 681–687. DOI: 10.1016/j.pain.2008.08.002.
  3. Naoki Inagaki, Katsuhiro Igeta, John Fan Kim, Masafumi Nagao, Noriko Shiraishi (2002): Involvement of unique mechanisms in the induction of scratching behavior in BALB/c mice by compound 48/80. In: European Journal of Pharmacology 448, S. 175–183.
  4. Liu, Qin; Tang, Zongxiang; Surdenikova, Lenka; Kim, Seungil; Patel, Kush N.; Kim, Andrew et al. (2009): Sensory neuron-specific GPCR Mrgprs are itch receptors mediating chloroquine-induced pruritus. In: Cell 139 (7), S. 1353–1365. DOI: 10.1016/j.cell.2009.11.034.
  5. Ehling, Sarah; Butler, Ashley; Thi, Stephanie; Ghashghaei, H. Troy; Bäumer, Wolfgang (2018): To scratch an itch: Establishing a mouse model to determine active brain areas involved in acute histaminergic itch. In: IBRO reports 5, S. 67–73. DOI: 10.1016/j.ibror.2018.10.002.
  6. Carstens, E.; Akiyama, Tasuku (2014): Chapter 12, Itch. Mechanisms and Treatment. Hoboken: Taylor and Francis (Frontiers in Neuroscience). Online verfügbar unter http://search.ebscohost.com/login.aspx?direct=true&scope=site&db=nlebk&db=nlabk&AN=694547