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.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
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Somatosensory and Chemosensory Systems Study Section (SCS)
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Sorensen, Roger
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Brown University
Schools of Medicine
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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
Polter, Abigail M; Bishop, Rachel A; Briand, Lisa A et al. (2014) Poststress block of kappa opioid receptors rescues long-term potentiation of inhibitory synapses and prevents reinstatement of cocaine seeking. Biol Psychiatry 76:785-93
Polter, Abigail M; Kauer, Julie A (2014) Stress and VTA synapses: implications for addiction and depression. Eur J Neurosci 39:1179-88
Brown, Travis E; Chirila, Anda M; Schrank, Benjamin R et al. (2013) Loss of interneuron LTD and attenuated pyramidal cell LTP in Trpv1 and Trpv3 KO mice. Hippocampus 23:662-71
Graziane, Nicholas M; Polter, Abigail M; Briand, Lisa A et al. (2013) Kappa opioid receptors regulate stress-induced cocaine seeking and synaptic plasticity. Neuron 77:942-54
Edwards, Jeffrey G; Gibson, Helen E; Jensen, Tyron et al. (2012) A novel non-CB1/TRPV1 endocannabinoid-mediated mechanism depresses excitatory synapses on hippocampal CA1 interneurons. Hippocampus 22:209-21
Niehaus, Jason L; Murali, Manjari; Kauer, Julie A (2010) Drugs of abuse and stress impair LTP at inhibitory synapses in the ventral tegmental area. Eur J Neurosci 32:108-17
Nugent, Fereshteh S; Niehaus, Jason L; Kauer, Julie A (2009) PKG and PKA signaling in LTP at GABAergic synapses. Neuropsychopharmacology 34:1829-42
Niehaus, Jason L; Cruz-Bermudez, Nelson D; Kauer, Julie A (2009) Plasticity of addiction: a mesolimbic dopamine short-circuit? Am J Addict 18:259-71
Nugent, Fereshteh S; Hwong, Alison R; Udaka, Yoko et al. (2008) High-frequency afferent stimulation induces long-term potentiation of field potentials in the ventral tegmental area. Neuropsychopharmacology 33:1704-12

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