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Control of spinal pain processing by strychnine-sensitive glycine and GABAA receptors

English title Control of spinal pain processing by strychnine-sensitive glycine and GABAA receptors
Applicant Zeilhofer Hanns Ulrich
Number 116064
Funding scheme Project funding
Research institution Institut für Pharmakologie und Toxikologie Universität Zürich
Institution of higher education University of Zurich - ZH
Main discipline Neurophysiology and Brain Research
Start/End 01.04.2007 - 31.03.2010
Approved amount 539'000.00
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Keywords (5)

pain; nociception; spinal cord; GABA-A receptor; glycine receptor

Lay Summary (English)

Lead
Lay summary
During evolution the physiological sensation of pain has evolved in all higher animals to protect their bodies from tissue damage. However, in inflammatory diseases and after nerve damage we often experience a pathological exaggeration of pain, which under unfortunate conditions can outlast the original cause and become chronic. In this situation, pain looses its physiological function and turns into a disease of its own right. Such chronic pain syndromes constitute a major medical and socio-economical problem worldwide, in particular because it often resists current medial treatment. It is meanwhile generally accepted that changes in the neuronal communications in the spinal cord dorsal horn are to a large extent responsible for many chronic pain syndromes. Within the last years it has become increasingly clear that a loss of inhibitory neurotransmission at this site, normally provided by the neurotransmitters g-aminobutyric acid (GABA) and glycine, is a key event in the generation and maintenance of pathological pain of inflammatory and neuropathic origin. A potentiation of the action of GABA and/or glycine at their dorsal horn receptors should therefore constitute a rational therapeutic strategy. In order to address the potential of inhibitory neurotransmitter receptors in the dorsal horn as analgesic drug targets, it is necessary to define their molecular identity and to better understand their function in dorsal horn nociceptive circuits under normal and pathological conditions. Our research focuses on two families of inhibitory neurotransmitter receptors: benzodiazepine-sensitive GABAA receptors and inhibitory (strychnine-sensitive) glycine receptors. It specifically aims at the identification of GABAA receptor isoforms relevant for spinal pain processing and at their function under normal and pathological conditions. We address these questions in an integrative approach combining pharmacological, behavioral and electrophysiological experiments in genetically engineered mice. The proposed experiments will provide a better understanding of the cellular and molecular basis of spinal pain control by inhibitory neurotransmission. They will help to determine whether drugs targeting GABAA receptors or strychnine-sensitive glycine receptors can be used to reverse inflammation- or injury-induced loss of spinal inhibition.
Direct link to Lay Summary Last update: 21.02.2013

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Number Title Start Funding scheme
131093 Control of spinal pain processing by strychnine-sensitive glycine and GABAA receptors 01.04.2010 Project funding

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