Starts:

Tuesday, September 20th
10:45am-12:15pm EDT

Category:

Topical Workshop

Tracks:

Mechanisms

Room

713 A/B

Schwann Cell Renaissance In Pain: Critical Appraisal Of New Knowledge On Old Cells

The primary reason for inadequate analgesic effects of current pharmaceuticals for neuropathic pain is that we do not fully understand the pathophysiological mechanisms that underlie its development. We will discuss ground-breaking novel findings on potential peripheral mechanisms of neuropathic pain concentrating on the skin-nerve interface and presenting potential implications on clinical practice. Data from clinical and preclinical studies will be discussed critically focusing on Schwann cells that are experiencing a renaissance, now in neuropathic pain pathophysiology. We will present new data that address whether or not skin Schwann cells are likely to be important in the generation or maintenance of neuropathic pain. The workshop will start with a presentation by Professor Campana, who will present new data on how extracellular vesicles from Schwann cells serve as multi-functional regulators of physiology and pathological changes, possibly controlling neuropathic pain. Associate Professor Karlsson will review the many challenges for quantifying Schwann cells, and he will compare Schwann cell densities between patients with and without diabetic neuropathy. Professor Üçeyler will present data from clinical studies with regard to cutaneous Schwann cells and patient-derived in vitro systems focusing on the skin-nerve interface and potential mechanisms that may contribute to the pathophysiology of neuropathic pain.

Presentations

Time
10:45am EDT12:15pm EDT

Nociceptor Sensitization – News From Patients and Patient-Derived In Vitro Systems at the Neuro-Cutaneous Unit

Tracks: Mechanisms
Categories: Topical Workshop
Neuropathic pain may be caused by diverse etiologies and it is intriguing that the same etiology may lead to a painful condition or remain painless. While until recently, pain generation and perception were exclusively associated with neuronal tissue, scientists have increasingly turned research focus to non-neuronal cells and their potential influence on the development of neuropathic pain. Skin cells are of particular interest since they tightly surround nociceptors and may influence nerve fiber growth and sensitivity. In this presentation, data on the potential influence of the neuro-cutaneous unit on neuropathic pain development will be summarized giving clinical examples and patient-derived in vitro systems. The audience will experience a lively and exciting journey spanning a bow from clinical research based on thorough pain phenotyping and biomaterial analysis to cutting-edge in vitro models that may guide the way to efficient systemic and local analgesic treatment.
10:45am EDT12:15pm EDT

Schwann Cell Extracellular Vesicles Are Innovative Regulators Of Neuroinflammation And Pain

Tracks: Mechanisms
Categories: Topical Workshop
Presented By: Dr. Wendy Campana

Several studies have revealed that Schwann cells (SCs) release small extracellular vesicles (EVs).

EVs are small nanovesicles and include exosomes.


Initially, exosomes were thought to be a cellular mechanism of waste disposal but are now also considered to be highly specific enablers of cellular communication
Importantly, exosomes reflect the status of their originating cells.


This talk will introduce novel SC EV mechanisms that regulate PNS physiology, 
during injury and

associated with the development of neuropathic pain. Focus will be on 1) proteins specifically sequestered in the plasma membranes of SC EVs that are bioactive, 2) SC EV tumor necrosis factor-receptor 1 (TNFR1) and how they serve as a TNF a

“decoy” and modify TNFα activities (including inhibiting stress activated cell signaling (p38 MAPK), regulate expression of other cytokines and influence SC morphology and viability), and 3) on novel ways that SC EVs modulate neuroinflammation and pain. The presentation will highlight the innovative aspects of SC EV biology, as it relates to neuropathic pain.
10:45am EDT12:15pm EDT

Schwann Cells In Patients With Painless and Painful Diabetic Peripheral Neuoropathy

Tracks: Mechanisms
Categories: Topical Workshop
Presented By: Dr. Pall R. Karlsson

The pathological hallmark in patients with painful neuropathies is a significant loss of intraepidermal nerve fibers. However, the simple count of intraepidermal nerve fibers does not explain why some, but not all, neuropathic patients develop neuropathic pain. It is, however, possible to perform much more detailed analysis of the skin biopsies. This talk will introduce new findings on detailed skin biopsy analysis related to neuropathic pain, with a special focus on the nociceptive Schwann cells. This specialized cutaneous glial cell type was recently introduced. However, the nociceptive Schwann cells have never been quantified before. Additionally, it remains unclear, whether or not there are morphological or functional differences of the Schwann cells between patients with and without neuropathic pain. Here, I will present novel ways to quantify the Schwann cells in both animal and human skin, address the many challenges and pitfalls when doing so, and present the nociceptive Schwann cell density in both animal models of type 1 diabetic DPN as well as in humans with type 1 diabetes, DPN without neuropathic pain and in patients with painful DPN, and correlate the findings with signs and symptoms of DPN.

Presenters

Professor Nurcan Üçeyler

Professor of Neurology
University of Würzburg

Dr. Wendy Campana

Professor
University of California

Dr. Pall R. Karlsson

Associate professor
Aarhus University