Project 4: Pathophysiology of Neuropathic Pain and Itch
Project Managers:
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About:
Chronic itch (pruritus), like chronic pain, is a common symptom in patients with polyneuropathies, e.g. caused by diabetes mellitus, HIV or chemotherapy. Both of these symptoms are predominantly mediated through small-caliber nerve fibers (C fibers, A-delta fibers). While mechanisms of neuropathic pain have been intensively investigated in recent years, there are hardly any data on the pathophysiology of neurogenic pruritus.
The primary aim of this project is to investigate the pathophysiology of these symptoms in patients with clinically proven polyneuropathy and differentially expressed pain and itch.
The following work packages are planned in detail:
The cooperation between the three university centers involved in the project allows both the implementation of methodologically very extensive and innovative research techniques as well as the recruitment of a large number of patients, which are necessary to answer the research questions. The project is synergistic with other subprojects in the consortium, e.g. with regard to the analysis of the spatial arrangement of immune cells and nerve fibers (cooperation with projects such as the Z project and projects, # 2, # 3, # 5).
In summary, we will investigate the pathophysiology of neurogenic pruritus in direct comparison to pain at the phenotypic, morphological and biochemical / immunological levels in one disorder (polyneuropathy), and we expect an improved understanding of the pathophysiology of neurogenic pruritus. This should then lead the way to new approaches for pruritus therapy.
The primary aim of this project is to investigate the pathophysiology of these symptoms in patients with clinically proven polyneuropathy and differentially expressed pain and itch.
The following work packages are planned in detail:
- The phenotype of patients with polyneuropathy and either pain or pruritus or a combination of both shall be evaluated on multiple levels. For this purpose, an detailled classification will be done, using clinical examination, questionnaires, psychophysical methods (quantitative sensory testing, QST), special neurophysiology of small-caliber nerve fibers and electrophoretic pruritus generation. We expect phenotypic patterns that distinguish polyneuropathy patients with pruritus from polyneuropathic patients with pain.
- We will investigate structural changes in skin innervation compared to healthy individuals and in comparisons between patients with polyneuropathy and pruritus and polyneuropathy and pain. The hypothesis is that altered spatial activation patterns of nociceptors may be a possible correlate for neuropathic prutitus.
- Local substances in the skin released by non-neuronal skin cells and immune cells and considered as potential mediators for pruritus and pain will be identified using qRT-PCR and immunohistochemistry.
The cooperation between the three university centers involved in the project allows both the implementation of methodologically very extensive and innovative research techniques as well as the recruitment of a large number of patients, which are necessary to answer the research questions. The project is synergistic with other subprojects in the consortium, e.g. with regard to the analysis of the spatial arrangement of immune cells and nerve fibers (cooperation with projects such as the Z project and projects, # 2, # 3, # 5).
In summary, we will investigate the pathophysiology of neurogenic pruritus in direct comparison to pain at the phenotypic, morphological and biochemical / immunological levels in one disorder (polyneuropathy), and we expect an improved understanding of the pathophysiology of neurogenic pruritus. This should then lead the way to new approaches for pruritus therapy.
Related Publications:
- Ruscheweyh R, Viehoff A, Tio J, Pogatzki-Zahn EM. Psychophysical and psychological predictors of acute pain after breast surgery differ in patients with and without pre-existing chronic pain. Pain 2017;158:1030-1038
- Pereira MP, Pogatzki-Zahn E, Snels C, Vu T, Üçeyler N, Loser K, Sommer C, Evers A, van Laarhoven AI, Agelopoulos K, Ständer S. There is no functional small-fiber neuropathy in prurigo nodularis despite neuroanatomical alterations. Exp Dermatol. 2017 Mar 31.
- Schneider G, Pogatzki-Zahn E, Marziniak M, Stumpf A, Ständer S. Cutaneous Sensory Function is Not Related to Depression and Anxiety in Patients with Chronic Pruritus with Dysesthetic Subqualities. Acta Derm Venereol. 2015;95:289-93.
- Fißmer I, Klein T, Magerl W, Treede RD, Zahn PK, Pogatzki-Zahn E. Modality-specific somatosensory changes in a human surrogate model of postoperative pa in. Anesthesiology 2011;115:387-397
- Ständer S, Pogatzki-Zahn E, Stumpf A, Fritz F, Pfleiderer B, Ritzkat A, Bruland P, Lotts T, Müller-Tidow C, Heuft G, Pavenstädt HJ, Schneider G, van Aken H, Heindel W, Wiendl H, Dugas M, Luger TA. Facing the Challenges of Chronic Pruritus: A Report From a Multi-disciplinary Medical Itch Centre in Germany. Acta Derm Venereol. 2015;95:266-71
- Raputova J, Srotova I, Sommer C, Üçeyler N , Birklein F, Rebhorn C, Rittner HL, Adamova B, Kovalova I, Nekvapilova E, Belobradkova J, Olsovsky J, Weber P, Dusek L, Jarkovsky J, Vlckova E, Bednarik J. Sensory phenotype and risk factors for painful diabetic neuropathy: a cross sectional observational study. Pain 2017, in press
- Schley M, Bayram A, Rukwied R, Dusch M, Konrad C, Benrath J, Geber C, Birklein F, Hägglöf B, Sjögren N, Gee L, Albrecht PJ, Rice FL, Schmelz M. Skin innervation at different depths correlates with small fibre function but not with pain in neuropathic pain patients. Eur J Pain. 2012;16:1414-25.
- Krämer HH, Rolke R, Bickel A, Birklein F. Thermal thresholds predict painfulness of diabetic neuropathies. Diabetes Care. 2004;27:2386-91.
- Leinders M, Doppler K, Klein T, Deckart M, Rittner H, Sommer C, Üçeyler N. Increased cutaneous miR-let-7d expression correlates with small nerve fiber pathology in patients with fibromyalgia syndrome. Pain 2016;157:2493-2503.
- Sommer C. Exploring pain pathophysiology in patients. Science 2016;354:588-592.