In Vivo Molecular Signal Transduction of Peripheral Mechanisms of Pain

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Author(s)

    • Ueda Hiroshi UEDA Hiroshi
    • Department of Molecular Pharmacology and Neuroscience, Nagasaki University School of Pharmaceutical Sciences

Abstract

Although we have obtained a number of pharmacological tools and mutant mice lacking specific genes related to the pain, the distinct molecular basis of the pain-producing mechanism has remained to be fully clarified since we have been using conventional paradigms of the nociception test that may drive multiple endogenous molecules affecting nociception at the same time. Here, I will introduce a new paradigm of the nociception test. In this test, we focused on polymodal C-fibers by measuring noci- ceptive flexor responses induced by the peripheral application of a single species of nociceptive molecule. In addition, we identified the site of drug actions on nociceptor endings by the fact that the nociception was abolished by the intrathecal pretreatment with antisense oligodeoxynucleotide for receptors. Throughout experiments using this paradigm of the nociception test, it was firstly revealed that substance P, a major neurotransmitter of polymodal C-fibers, directly stimulates nociceptor endings through activation of G<SUB>q/11</SUB> and phospholipase C, followed by Ca<SUP>2+</SUP> influx through plasma membrane-bound inositol trisphosphate receptors, and that bradykinin and histamine, both endogenous representative pain-producing substances, share this mechanism. Another unique mechanism is through G<SUB>i</SUB>-coupled receptors such as receptors for nociceptin (orphanin FQ) or kyotorphin (tyrosine-arginine). The latter mechanism was found to be mediated through a substance P release from nociceptor endings. Future studies including some modifications of this paradigm should be also clinically useful for neuropathic pain research as well as understanding of pain physiology.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 79(3), 263-268, 1999-03-01

    The Japanese Pharmacological Society

References:  27

Cited by:  1

Codes

  • NII Article ID (NAID)
    10008682585
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    4698955
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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