University of Surrey

Test tubes in the lab Research in the ATI Dance Research

Adenosine A2A Receptors and Peripheral Nociception.

Hussey, Martin John. (2007) Adenosine A2A Receptors and Peripheral Nociception. Doctoral thesis, University of Surrey (United Kingdom)..

[img]
Preview
Text
27605350.pdf
Available under License Creative Commons Attribution Non-commercial Share Alike.

Download (6MB) | Preview

Abstract

Adenosine is a neuromodulator with complex effects on nociceptive pathways. Mice lacking the adenosine A2A receptor are hypoalgesic and a role for the A2A receptor in sensitizing afferent fibres projecting to the spinal cord has been suggested. To test this hypothesis adenosine A2A receptor knockout mice and wildtype controls were used in behavioural and autoradiographic experiments. Adenosine A2A receptor knockout mice had substantially reduced spinal cord NMDA glutamate binding whereas spinal cord AMPA glutamate receptor binding was increased, spinal cord substance P receptor binding was unaffected. Additionally, there was reduced uptake of [14C]-2-deoxyglucose into spinal cord sections from adenosine A2A receptor knockout mice. In the formalin test there was a significant reduction in nociceptive behaviour displayed by adenosine A2A receptor knockout mice during both phases of the test. The selective adenosine A2A antagonist SCH58261 also antagonized both phases of the formalin test in wildtype mice. Spinal cord NMDA glutamate receptor binding was significantly reduced following formalin injection in wildtype mice whereas AMPA glutamate receptor binding and uptake of [14C]-2-deoxyglucose were significantly increased following formalin injection in wildtype mice. There were no significant changes in any of the measures examined in spinal cords from adenosine A2A receptor knockout mice. Following repeated PGE2 injection and mechanical paw pressure, spinal cord NMDA glutamate receptor binding and uptake of [14C]-2-deoxyglucose into the spinal cord was significantly greater in adenosine A2A receptor knockout mice compared to wildtype mice. This may reflect loss of inhibitory adenosine A2A receptors located on inflammatory cells. The reduced response to formalin injection and decrease in NMDA glutamate receptor binding could reflect reduced peripheral sensory input to the spinal cord and be responsible for the hypoalgesia in adenosine A2A receptor knockout mice. These results support a key role for adenosine A2A receptors in peripheral nociceptive pathways.

Item Type: Thesis (Doctoral)
Divisions : Theses
Authors : Hussey, Martin John.
Date : 2007
Additional Information : Thesis (Ph.D.)--University of Surrey (United Kingdom), 2007.
Depositing User : EPrints Services
Date Deposited : 06 May 2020 11:53
Last Modified : 06 May 2020 11:53
URI: http://epubs.surrey.ac.uk/id/eprint/855532

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year


Information about this web site

© The University of Surrey, Guildford, Surrey, GU2 7XH, United Kingdom.
+44 (0)1483 300800