Switching of Bradykinin-Mediated Nociception Following Partial Sciatic Nerve Injury in Mice

Harunor Rashid, Makoto Inoue, Misaki Matsumoto, Hiroshi Ueda

Research output: Contribution to journalArticlepeer-review


Bradykinin (BK) is well known as a potent mediator of pain and hyperalgesia. Using a highly sensitive nociception test, we found that intraplantar (i.pl.) injection of BK produced nociceptive hyper-responses in partial sciatic nerve-injured mice, compared with the control sham-operated animals. By use of selective agonists and antagonists, we revealed that BK nociception in sham-operated mice was mediated through B2 receptor, whereas that in injured mice was mediated through B1 receptor. When we examined the activation of extracellular signal-regulated protein kinase (ERK) in dorsal root ganglion (DRG) neurons upon i.pl. injection of BK, phosphorylated ERK was mainly observed in unmyelinated neurons in sham-operated mice, and in case of nerve-injured mice, ERK was mainly activated in myelinated neurons and satellite cells. The B1 receptor agonist, [Lys-des-Arg9]-BK also produced nociceptive response and activated ERK only in nerve-injured mice. BK or B1 agonist-induced activation of ERK in DRG neurons of nerve-injured mice was completely blocked by pretreatment with antisense oligodeoxynucleotide (AS-ODN) for B1 receptor. We found that in sham-operated mice mainly B2 receptors were expressed in unmyelinated DRG neurons with a very little presence of B1 receptor. After nerve injury, B2 receptor expression drastically decreased, whereas B1 receptors were newly expressed mainly in myelinated DRG neurons and satellite cells. Finally, BK nociception in sham-operated mice was blocked by AS-ODN for B2 receptors and that in injured mice by AS-ODN for B1 receptors. Altogether, these findings confirm a switching of receptor and fiber subtype for BK nociception after peripheral nerve injury, which might contribute to the pathobiology of neuropathic pain.

Original languageEnglish (US)
Pages (from-to)1158-1164
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number3
StatePublished - Mar 2004
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology


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