A novel mechanism of chronic pain will be explored: the excitatory effects of the immunoglobulin G (IgG) immune complex on primary sensory afferents via neuronal Fc gamma receptor I (Fc3RI). Chronic pain often accompanies autoimmune, allergic or infectious diseases involving antigen-specific immune responses in the peripheral tissue, nerve or sensory ganglia though the underlying mechanisms are largely unknown. A common feature among these disorders is the elevated level of antigen-specific IgG in the serum and the presence of IgG immune complex in the affected tissue. Recently it was discovered that a subpopulation of dorsal root ganglion neurons with nociceptive properties expressed the high-affinity IgG receptor, Fc3RI and could be directly activated by IgG immune complex. Preliminary data indicate that cutaneous hyperalgesia in skin challenged with antigen in previously immunized rats long outlasts signs of acute inflammation. I propose to explore the effects of a specific foreign antigen, applied to the skin or to the spinal ganglia, in immunized vs. unimmunized rats, on the excitability and neurochemical properties of functionally identified nociceptive primary sensory neurons in relation to Fc3RI and pain-related behaviors. This study will reveal a novel mechanism of chronic pain driven by the antigen-specific immune response via the effects of IgG immune complex on the Fc receptors expressed in primary sensory neurons. It will provide potentially new therapeutic strategies in the treatment of chronic pain.

Public Health Relevance

This study will reveal a novel mechanism of chronic pain driven by the antigen-specific immune response via the effects of IgG immune complex on the Fc receptors expressed in primary sensory neurons. It will provide potentially new therapeutic strategies in the treatment of chronic pain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21NS065091-02
Application #
7760594
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Porter, Linda L
Project Start
2009-02-01
Project End
2011-07-31
Budget Start
2010-02-01
Budget End
2011-07-31
Support Year
2
Fiscal Year
2010
Total Cost
$215,047
Indirect Cost
Name
Yale University
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520