Friday, September 23rd
4:30pm-6:00pm EDT


Topical Workshop




716 A

Novel Peripheral Mechanisms of Neuro-immune Crosstalk in Chronic Pain

This workshop will elucidate novel mechanisms whereby non-neuronal cells in peripheral tissues drive neuroinflammation and chronic pain. New data will be presented that reveal important roles for keratinocytes, adipocytes (fat cells), muscle macrophages, and B cells in the onset and maintenance of different types of chronic pain. In the first presentation, Dr. Matthieu Talagas will describe physical and functional connections between epidermal keratinocytes and nociceptive sensory neurons essential for the transduction of nociceptive input. In the second presentation, Dr. Andrea Nackley will describe how catecholamine activation of adipocyte Adrb3 leads to immune remodeling, enhanced nociceptor activity, and central sensitization in a mouse model of chronic overlapping pain conditions (COPCs). In the third presentation, Dr. Kathleen Sluka will describe key muscle-immune-neuro interactions that lead to hyperalgesia in response to an acute bout of physical activity and those that lead to analgesia in a mouse model of widespread musculoskeletal pain. In the fourth presentation, Dr. Peter Grace will describe how injury-induced B cell differentiation in lymphoid organs results in formation of (auto)antibody-antigen complexes that drive neuropathic pain. Upon completion of this session, attendees will be able to 1) define unique mechanisms whereby peripheral keratinocytes, adipocytes, muscles, and immune cells drive nociception and pain, 2) describe how these mechanisms are modified by genetic (eg, sex) and/or environmental (eg, stress) factors, and 3) recognize the potential utility of peripherally-targeted treatments for chronic pain.


4:30pm EDT6:00pm EDT

B Cell Regulation of Neuropathic Pain

Tracks: Mechanisms
Categories: Topical Workshop
Presented By: Dr. Peter M. Grace

Our unbiased transcriptome screens suggested that enhanced B cell signaling is an under-appreciated consequence of injury. New data will be presented to demonstrate that B cells are necessary for initiation of neuropathic pain. We show that constitutive deficiency or pharmacological depletion of B cells protects male and female mice from neuropathic pain. As the key mechanism, antibodies secreted by differentiated B cells form complexes with autoantigens induced by the sterile injury, and activate Fc gamma receptors along the pain neuraxis. Moreover, evidence for elevated antibodies in CSF of patients with neuropathic pain will be presented. Together, these data implicate a new, clinically-relevant cell-signaling axis in maintaining pain after traumatic nerve injury.

4:30pm EDT6:00pm EDT

Keratinocytes and Intra-epidermal Nerve Endings: Two Close Nociceptive Transducers

Tracks: Mechanisms
Categories: Topical Workshop

Intra-epidermal free nerve endings (FNEs), which are described as passing freely between the epidermal keratinocytes, are conventionally thought to be the exclusive transducers of noxious thermal, mechanical or chemical stimuli. Keratinocytes are considered to be merely physical support for FNEs.
This simplistic opposition between nociceptive sensory neurons and keratinocytes, however no longer needs to be. Not only can epidermal keratinocytes modulate the transduction in nociceptive sensory neurons, but they also have recently emerged as primary nociceptive transducers as a supplement to sensory neurons. Moreover, the identification of en passant chemical synaptic-like contacts between keratinocytes and sensory neurons has recently thrown light on a potential two-receptor-site, each conveying specific aspects of pain, similar to Merkel cells and the Aß nerve fibres in the Merkel complexes for touch. In addition, FNEs can also progress within keratinocyte ensheathments, an evolutionarily conserved cellular process which potentiates the nociceptive function of FNEs in animal models. Therefore, “FNEs” are not free, but connected to keratinocytes both physically and functionally.
These findings shed a new light on the pathophysiology of pain and may call for a reassessment of basic assumptions in cutaneous sensory perception.

4:30pm EDT6:00pm EDT

Role of Resident Macrophages in Exercise-induced Pain and Analgesia

Tracks: Mechanisms
Categories: Topical Workshop
Presented By: Dr. Kathleen A. Sluka

An acute bout of physical activity in an individual with chronic pain can enhance pain, while regular physical activity reduces pain. Interactions between muscle, immune cellsand nociceptors have emerged as a key initiator of dichotomous responses to physical activity t. Acute bouts of activity release fatigue metabolites from muscle that interact with receptors on macrophages to promote nociception in a sedentary animal through release of IL-1beta or anti-nociception in a physically active animal through release of IL-4 and IL-10. We will present data showing a sex-dependent mechanism whereby activation of purinergic receptor P2X7 enhances release of IL-1beta through NLRP3 and caspase-1 in sedentary male, but not female mice. Lastly, we will show translational data examining immune changes in monocytes in individuals with fibromyalgia. These data examine key muscle-immune-neuro interactions that lead to hyperalgesia or analgesia in response to physical activity.

4:30pm EDT6:00pm EDT

The Role of Adipocytes in Chronic Pain and Inflammation

Tracks: Mechanisms
Categories: Topical Workshop
Presented By: Dr. Andrea G Nackley

The origin of chronic overlapping pain conditions (COPCs), such as temporomandibular disorder and fibromyalgia, is linked to enhanced catecholaminergic tone. In earlier work, we provided the first demonstration that catecholamines promote chronic multi-site pain through activation of adrenergic receptor beta-3 (Adrb3). Here, new data will be presented in a clinically-relevant mouse model of COPCs that reveal Adrb3 mediates chronic multi-site pain through its location on peripheral adipocytes (fat cells). Activation of adipocyte Adrb3 leads to stimulation of pro-inflammatory cytokines and enhanced activity of primary afferent nociceptors. The resulting pain is then maintained by neuroplastic changes in the central nervous system that are characterized by increased production of pro-inflammatory cytokines, phosphorylation of mitogen-activated protein kinases (MAPKs), and increased activation of glia and nociceptors.


Dr. Peter M. Grace

Associate Professor and Chair ad interim
MD Anderson Cancer Center

Dr. Andrea G Nackley

Associate Professor
Duke University

Dr. Kathleen A. Sluka

University of Iowa

Professor Matthieu Talagas

Brest University Hospital / University of Western Brittany