Asako Kubo

Publications (2)6.97 Total impact

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

  Asako Kubo, Kimiaki Katanosaka, Kazue Mizumura
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  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 extracellular solution and pretreatment of the neurone culture with chondroitinase ABC attenuated this low pH-induced sensitization in IB4-positive neurones. These findings suggest that a change in interaction between mechanosensitive channels and/or their auxiliary molecules and the side chain of versican on the cell surface causes this sensitization, at least in IB4-positive neurones. This report proposes a novel mechanism for sensitization that involves extracellular proteoglycans (versican).
  The Journal of Physiology 05/2012; 590(Pt 13):2995-3007. · 4.72 Impact Factor
• Article: Absence of mechanical hyperalgesia after exercise (delayed onset muscle soreness) in neonatally capsaicin-treated rats.

  Asako Kubo, Michiyo Koyama, Ryoko Tamura, Yoshiko Takagishi, Shiori Murase, Kazue Mizumura
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  ABSTRACT: Delayed onset muscle soreness (DOMS) appears with some delay after unaccustomed, strenuous exercise, especially after lengthening contraction (LC). It is characterized by tenderness and movement related pain, namely muscular mechanical hyperalgesia. To clarify the involvement of C-fibers in this mechanical hyperalgesia, we examined whether DOMS could be induced in rats treated neonatally with capsaicin. We confirmed that a large portion of unmyelinated afferent fibers were lost in capsaicin treated rats. In these animals, LC failed to induce muscular mechanical hyperalgesia. mRNA of nerve growth factor (NGF) in the muscle, which plays a pivotal role in maintaining mechanical hyperalgesia, was upregulated in the capsaicin treated animals similar to the vehicle treated animals. These results demonstrate that C-fiber afferents are essential in transmitting the nociceptive information from exercised muscle in DOMS.
  Neuroscience Research 02/2012; 73(1):56-60. · 2.25 Impact Factor