Mice lacking acid-sensing ion channels (ASIC) 1 or 2, but not ASIC3, show increased pain behaviour in the formalin test
Article first published online: 9 JAN 2012
2009 European Federation of Chapters of the International Association for the Study of Pain
European Journal of Pain
Volume 13, Issue 6, pages 554–563, July 2009
How to Cite
Staniland, A. A. and McMahon, S. B. (2009), Mice lacking acid-sensing ion channels (ASIC) 1 or 2, but not ASIC3, show increased pain behaviour in the formalin test. European Journal of Pain, 13: 554–563. doi: 10.1016/j.ejpain.2008.07.001
- Issue published online: 9 JAN 2012
- Article first published online: 9 JAN 2012
- Received 14 January 2008; received in revised 21 April 2008; accepted 13 July 2008
- Transgenic mice
Extracellular acidification is a component of the inflammatory process and may be a factor driving the pain accompanying it. Acid-sensing ion channels (ASICs) are neuronal proton sensors and evidence suggests they are involved in signalling inflammatory pain. The aims of this study were to (1) clarify the role of ASICs in nociception and (2) confirm their involvement in inflammatory pain and determine whether this was subunit specific.
This was achieved by (1) direct comparison of the sensitivity of ASIC1, ASIC2, ASIC3 and TRPV1 knockout mice versus wildtype littermates to acute thermal and mechanical noxious stimuli and (2) studying the behavioural responses of each transgenic strain to hind paw inflammation with either complete Freund's adjuvant (CFA) or formalin.
Naïve ASIC1−/− and ASIC2−/− mice responded normally to acute noxious stimuli, whereas ASIC3−/− mice were hypersensitive to high intensity thermal stimuli. CFA injection decreased mechanical and thermal withdrawal thresholds for up to 8days. ASIC2−/− mice had increased mechanical sensitivity on day 1 post-CFA compared to wildtype controls. TRPV1−/− mice had significantly reduced thermal, but not mechanical, hyperalgesia on all days after inflammation. Following formalin injection, ASIC1−/− and ASIC2−/−, but not ASIC3−/− or TRPV1−/−, mice showed enhanced pain behaviour, predominantly in the second phase of the test.
These data suggest that whilst ASICs may play a role in mediating inflammatory pain, this role is likely to be modulatory and strongly dependent on channel subtype.