Extracellular matrix proteoglycan plays a pivotal role in sensitization by low pH of mechanosensitive currents in nociceptive sensory neurones.

The Journal of Physiology
Asako KuboKazue Mizumura

Abstract

Ischaemia, inflammation, and exercise lead to tissue acidosis, which induces pain and mechanical hyperalgesia. Corresponding to this, enhanced thin-fibre afferent responses to mechanical stimulation have been recorded in vitro at low pH. However, knowledge about how this sensitization by low pH occurs is lacking. In this study, we found that all three types (rapidly adapting (RA), intermediately adapting and slowly adapting) of mechanically activated currents recorded with the whole cell patch-clamp method were sensitized by low pH in rat cultured dorsal root ganglion neurones. This sensitization was mainly observed in neurones positively labelled with isolectin B4 (IB4), which binds to versican, a chondroitin sulfate proteoglycan. Inhibitors of acid-sensitive channels (amiloride and capsazepine) did not block sensitization by low pH except in RA neurones, and extracellular calcium was not involved even in the sensitization of this type of neurone. A broad spectrum kinase inhibitor and a phospholipase C inhibitor (staurosporine and U73122) failed to block pH-induced sensitization in IB4-positive neurones, suggesting that these intracellular signalling pathways are not involved. Notably, both excess chondroitin sulfate in the ex...Continue Reading

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Citations

Aug 24, 2012·Journal of Neurophysiology·Pedro AlvarezJon D Levine
Jun 27, 2013·PloS One·Hiroki OtaKazue Mizumura
Sep 13, 2013·Sports Medicine·Ebonie RioJill Cook
Apr 8, 2015·Journal of Neurochemistry·Oliver BogenFerdinand Hucho
May 29, 2013·Pain·David B ReichlingJon D Levine
Dec 15, 2018·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Bruce A CorlissShayn M Peirce
Dec 19, 2013·Pain·David B ReichlingJon D Levine

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