Following peripheral injury, changes in tactile perception develop, including primary and secondary hyperalgesia and allodynia. A loss of GABAergic or glycinergic inhibition is one mechanism that can cause these changes in pain perception. Inhibitory neurons in the dorsal horn play a key role in controlling the flow of nociceptive information through ascending pathways to the brain where it is perceived as painful. Interleukin-1beta (IL-1beta) is an inflammatory cytokine released in the spinal cord during injury and is known to promote pain and cause hyperalgesia when introduced into the spinal cord. Using electrophysiological methods in spinal cord slices, we have found that IL-1beta upregulates inhibitory glycine receptors on inhibitory neurons in the dorsal horn. The rapid inhibition of inhibitory neurons is expected to promote the transmission of pain signals to the brain, and thus may explain how IL-1beta causes pain. Our preliminary results indicate that inflammation in vivo potentiates glycinergic synapses similarly to IL-1beta potentiation observed in vitro. IL-1beta is also released during neuropathic pain, and here we propose to test whether glycinergic neurotransmission on inhibitory interneurons in the pain pathway is upregulated in a model of neuropathic pain. Our work could suggest novel drug targets for the treatment of persistent pain conditions that are currently difficult to treat effectively.

Public Health Relevance

The dorsal horn of the spinal cord is the first central nervous system processing station for pain signals, and one way pain signals can be altered rapidly after injury is through changes in synaptic strength. My laboratory has identified a novel persistent synaptic alteration in the dorsal horn triggered by a compound released during inflammatory injury. The experiments in this application test whether this form of synaptic plasticity is an essential component of neuropathic pain, and could provide a novel strategy for the treatment of persistent pain.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
3R01DA011289-15S1
Application #
8552221
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Sorensen, Roger
Project Start
1997-07-15
Project End
2014-08-31
Budget Start
2013-09-30
Budget End
2014-08-31
Support Year
15
Fiscal Year
2013
Total Cost
$121,875
Indirect Cost
$46,875
Name
Brown University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
001785542
City
Providence
State
RI
Country
United States
Zip Code
02912
Chirila, Anda M; Brown, Travis E; Bishop, Rachel A et al. (2014) Long-term potentiation of glycinergic synapses triggered by interleukin 1?. Proc Natl Acad Sci U S A 111:8263-8
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