Activated Glia: Targets for the Treatment of Neuropathic Pain

With Support From:

MediciNova Logo

MediciNova, Inc.

 
Endo Logo

Endo Pharmaceuticals, Inc.

 

Purdue Pharma LP

Purdue Pharma LP

Organizers
Mark S. Cooper (U. Washington)
Donald C. Manning (Shionogi USA, Inc.)
Kirk W. Johnson (MediciNova, Inc.)

Location
Four Points by Sheraton, Chicago O'Hare Airport Hotel
(Map and Directions)

Workshop is by invitation only. Please contact Debra Nelson-Hogan (Tel: 212.532.4794, Email: dhogan@seersha.com) for registration information.

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As activated glia have been correlated with a number of neuroinflammatory and neurodegenerative disorders, the RSDSA will bring together basic researchers and clinicians to jointly evaluate the development of glial attenuators for the treatment of neuropathic pain disorders, including complex regional pain syndrome (CRPS),1 and other chronic illnesses.

Researchers and clinicians can play pivotal roles in determining the direction that research should take on this topic. The meeting will provide a forum whereby the role of activated glia—including specific cell types and molecular mechanisms—can be critically reviewed and discussed. The meeting will also discuss the development of differential diagnostic tools, such as PET and MRI contrast enhancement techniques, to detect and/or visualize the presence of activated glia in patients with chronic pain in the central nervous system.

1. Del Valle L, Schwartzman RJ, Alexander G. Spinal cord histopathological alterations in a patient with longstanding complex regional pain syndrome. Brain Behav Immun. 2009;23:85-91.


 

Brain resident microglial cells are normally highly motile and rapidly respond to neural tissue injury. Here, a multiphoton laser microscope was used to collect fluorescent images of microglia (green) in a live brain tissue slice harvested from a neonatal mouse. The tissue was taken from a genetically altered mouse that expresses green fluorescent protein (GFP) in the microglial cells, thereby rendering the cells fluorescent. In normal brain, microglial cells actively survey the brain tissue environment by extending and retracting branches in random directions. This motile activity is captured here during a 16 minute baseline period. Subsequently, a brief pulse of high-intensity laser light was used to induce localized tissue damage along a line between the white arrowheads (white bar at 00:17). Cells injured by the laser become labeled with a red dye (Sytox Orange), which binds to DNA in the nucleus of injured cells. Within minutes after injury, nearby microglia undergo a process termed 'activation' which involves extension of branches preferentially towards the injured cells. Microglial cells then begin to migrate toward and accumulate at the injury site. The chemotaxic movement of microglial cells likely results from release of ATP from injured cells. Total sequence time is ~2 hr. Time is shown in hr:min. (Courtesy Michael Dailey, University of Iowa)

   
   

 

Workshop Agenda

Thursday

 

7:00-9:00 pm

Opening Reception

 

 

Friday

 

8-8:30 am

Workshop Overview and Perspectives

Don Manning, MD, PhD
Shionogi USA
View Papers

 

 

 

Pharmacotherapy: Progress and Challenges
Moderator: Kirk Johnson, PhD

 

 

 

8:30-9:10 am

A critical assessment of glial activation in pain regulation

Joyce DeLeo, PhD

Dartmouth Medical School

View Papers

 

 

 

9:10-9:30 am

Question and Answer Session

 

 

 

 

9:30-10:10 am

Ibudilast in Pain and Other Neurological Disorders

Kirk Johnson, PhD
MediciNova
View Papers

 

 

 

10:10-10:30 am

Question and Answer Session

 

 

 

 

10:30-10:45 am

Break

 

 

 

 

10:45-11:25 am

Controlling neuroinflammation by targeting specific glial receptors: implications for pain and beyond

Linda Watkins, PhD

University of Colorado

View Papers

 

 

 

11:25-11:45 am

Question and Answer Session

 

 

 

 

11:45 am-1:00 pm

Lunch and Networking

 

     
11:45 am Common Inflammatory Mechanisms in MS and CRPS (RSD) Robert Knobler, MD
     
12:00 pm Nerve Injury, Neuroinflammation, and Cervical Dystonia Ken Price
President, National Spasmodic Torticollis Association
     

 

 

 

 

Activated Glia in Supraspinal Sites
Moderator: Joshua Prager, MD, MS

 

 

 

1:00-1:40 pm

Activated Microglia and the 18kD Translocator protein

Richard Banati, MD, PhD

University of Sydney

View Papers

 

 

 

1:40-2:00 pm

Question and Answer Session

 

 

 

 

2:00-2:30 pm

Using Positron Emission Tomography to image activated glia in the brain

Diana Martinez, MD

Columbia University
View Papers

 

 

 

2:30-2:45 pm

Question and Answer Session

 

 

 

 

2:45-3:15 pm

Potential Roles of Activated Supraspinal Glia in the Modulation of Neuropathic Pain

Michael Ossipov, PhD

University of Arizona
View Papers

 

 

 

3:15-3:35 pm

Question and Answer Session

 

 

 

 

3:35-3:50 pm

Break

 

 

 

 

 

Imaging Activated Microglia
Moderator: Michael Dailey, PhD

 

 

 

3:50-4:20 pm

Imaging Microglia Activation in Live Tissues

Michael Dailey, PhD

University of Iowa

View Papers

 

 

 

4:20-4:35 pm

Question and Answer Session

 

 

 

 

4:35-5:05 pm

Pharmacological validation of two molecular imaging agents targeting proteins expressed by microglia

Nephi Stella, PhD

University of Washington

View Papers

 

 

 

5:05-5:20 pm

Question and Answer Session

 

 

 

 

5:20-5:50 pm

Multifunctional Nanoparticles for Neuroimaging

Miqin Zhang, PhD

University of Washington
View Papers

 

 

 

5:50-6:15 pm

Question and Answer Session

 

 

 

 

6:45-9:30 pm

Dinner and Networking

 


Keynote Address
Clinical Trials and Neuropathic Pain: Do Mechanistic Approaches Offer Hope?

A bus will transport attendees to Basilico’s Ristorante nearby


James Campbell, MD
Johns Hopkins University
View Papers

 

Saturday

 

 

Linking Glial Activation with Pathophysiology
Moderator: R. Norman Harden, MD

 

 

 

8:00-8:30 am

CRPS: Signs, Symptoms, Tests and their Hypothetical Link to Glial Activation

R. Norman Harden, MD
Rehabilitation Institute of Chicago, Center for Pain Management

View Papers

 

 

 

8:30-8:45 am

Question and Answer Session

 

 

 

 

8:45-9:15 am

Fighting Activated Glia and Closing Opened Pain Gates by Increasing Spinal Inhibition

Theodore Price, PhD

University of Arizona
View Papers

 

 

 

9:15-9:30 am

Question and Answer Session

 

 

9:30-10:00 am

Beneficial and Pathological Microglial Phenotypes in Neuroinflammatory Disorders

Thomas Möller, PhD

University of Washington

View Papers

 

 

 

10:00-10:15 am

Question and Answer Session

 

 

 

 

10:15-10:45 am

Break and Networking

 

 

 

 

 

Building Knowledge Consortia to Address Neuropathic Pain
Moderator: Mark S. Cooper, PhD

 

 

 

11:00-11:30 am

The TREND Knowledge Consortium: Perspectives on Activated Glial Research in CRPS I

Roberto S. G. M. Perez, PhD

VU University Medical Center, Amsterdam, Steering Committee Member of TREND

View Papers

 

 

 

12:00- 1:00 pm

Lunch

 

 

 

 

1:00-3:00 pm

Work Groups

Moderators: Mark S. Cooper, PhD, and Peter Moskovitz, MD 

 

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Workshop Synopsis

Activated Glia: Targets for the Treatment of Neuropathic Pain, Peter A Moskovitz, MD, and Mark S. Cooper, PhD (reprinted with permission from Practical Pain Management)

Papers from Speakers

Richard Banati (University of Sydney)

Brain plasticity and microglia: is transsynaptic glial activation in the thalamus after limb denervation linked to cortical plasticity and central sensitisation?

Evidence of widespread cerebral microglial activation in amyotrophic lateral sclerosis: an [11C](R)-PK11195 positron emission tomography study

Long-term trans-synaptic glial responses in the human thalamus after peripheral nerve injury

Positron Emission Tomography Imaging of Neuroinflammation

Visualising Microglial Activation In Vivo

 

James Campbell (Johns Hopkins University)

Mechanisms of Neuropathic Pain

Nerve Lesions and the Generation of Pain

 

Michael Dailey (University of Iowa)

Dynamics of Microglial Activation: A Confocal Time-Lapse Analysis in Hippocampal Slices

Purines Induce Directed Migration and Rapid Homing of Microglia to Injured Pyramidal Neurons in Developing Hippocampus

 

Joyce DeLeo (Dartmouth Medical School)

Cannabinoid receptor type 2 activation induces a microglial anti-inflammatory phenotype and reduces migration via MKP induction and ERK dephosphorylation

CNS-infiltrating CD4+ T lymphocytes contribute to murine spinal nerve transection-induced neuropathic pain

Efficacy of propentofylline, a glial modulating agent, on existing mechanical allodynia following peripheral nerve injury

Morphine Enhances Microglial Migration through Modulation of P2X4 Receptor Signaling

Neuroimmune interactions and pain: Focus on glial-modulating targets

 

Norman Harden (Rehabilitation Institute of Chicago, Center for Pain Management)

Complex regional pain syndrome: are there distinct subtypes and sequential stages of the syndrome?

Proposed New Diagnostic Criteria for Complex Regional Pain Syndrome

The Brain in Chronic CRPS Pain: Abnormal Gray-White Matter Interactions in Emotional and Autonomic Regions

 

Kirk Johnson (MediciNova)

Reduction of opioid withdrawal and potentiation of acute opioid analgesia by systemic AV411 (ibudilast)

The glial modulatory drug AV411 attenuates mechanical allodynia in rat models of neuropathic pain

 

Donald Manning (Shionogi USA)

New and Emerging Pharmacological Targets for Neuropathic Pain

The Role of Neuroimmune Activation in Chronic Neuropathic Pain and New Targets for Therapeutic Intervention

 

Diana Martinez (Columbia University)

Lower Level of Endogenous Dopamine in Patients With Cocaine Dependence: Findings From PET Imaging of D2/D3 Receptors Following Acute Dopamine Depletion

Alcohol Dependence Is Associated with Blunted Dopamine Transmission in the Ventral Striatum

 

Thomas Möller (University of Washington)

Neuroinflammation in Huntington’s disease

A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington’s disease

Experimental autoimmune encephalomyelitis disrupts endocannabinoid-mediated neuroprotection

Microglia Biology in Health and Disease

Neuroinflammation in the pathogenesis of amyotrophic lateral sclerosis

 

Michael Ossipov (University of Arizona)

Descending Facilitation from the Rostral Ventromedial Medulla Maintains Nerve Injury-induced Central Sensitization

Glial activation in the rostroventromedial medulla promotes descending facilitation to mediate inflammatory hypersensitivity

 

Roberto Perez (VU University Medical Center, Amsterdam, Steering Committee Member of TREND [Trauma Related Neuronal Dysfunction])

Evidence based guidelines for complex regional pain syndrome type 1

Intravenous Magnesium for Complex Regional Pain Syndrome Type 1 (CRPS 1) Patients: A Pilot Study

The treatment of complex regional pain syndrome type I with free radical scavengers: a randomized controlled study

 

Ted Price (University of Arizona)

Acetazolamide and midazolam act synergistically to inhibit neuropathic pain

Chloride regulation in the pain pathway

 

Nephi Stella (University of Washington)

Binding of NIR-conPK and NIR-6T to Astrocytomas and Microglial Cells: Evidence for a Protein Related to TSPO

Endocannabinoid signaling in microglial cells

 

Linda Watkins (University of Colorado)

Pathological and protective roles of glia in chronic pain

The glial activation inhibitor AV411 reduces morphine-induced nucleus accumbens dopamine release

The ‘‘Toll’’ of Opioid-Induced Glial Activation: Improving the Clinical Efficacy of Opioids by Targeting Glia

 

Miqin Zhang (University of Washington)

Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging

Specific Targeting of Brain Tumors with an Optical/Magnetic Resonance Imaging Nanoprobe across the Blood-Brain Barrier

 

Other Papers

Emerging Importance of Neuron-Satellite Glia Interactions within Trigeminal Ganglia in Craniofacial Pain

 

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