In vivo signal transduction of tetrodotoxin-sensitive nociceptive responses by substance P given into the planta of the mouse hind limb

Cell Mol Neurobiol. 1998 Oct;18(5):555-61. doi: 10.1023/a:1026335611162.

Abstract

1. We developed a simple and sensitive peripheral analgesic test in mice. 2. Substance P (SP) given into the planta (i.pl.) of the mouse hind limb produced a flexor response. The flexor response was dependent on SP doses (0.1-100 pmol, i.pl.). When SP (10 pmol) was given every 5 min, there were stable flexor responses. These nociceptive responses were completely abolished by CP-96,345, a neurokinin 1 receptor antagonist. 3. SP-induced responses were also blocked by several signal transduction-related compounds, such as tetrodotoxin, EGTA, and U73122, a selective phospholipase C inhibitor. 4. These findings suggest that SP depolarizes peripheral nerve endings, possibly through inositol trisphosphate (Ins P3)-gated Ca2+ influx, followed by induction of action potentials in the peripheral axons of primary afferent neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Afferent Pathways / physiology
  • Animals
  • Biphenyl Compounds / pharmacology
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology
  • Egtazic Acid / pharmacology
  • Estrenes / pharmacology
  • GTP-Binding Proteins / physiology
  • Hindlimb / innervation
  • Inositol 1,4,5-Trisphosphate / physiology
  • Ion Transport
  • Male
  • Mice
  • Mice, Inbred Strains
  • Models, Neurological
  • Muscle Contraction / drug effects*
  • Muscle Contraction / physiology
  • Neurons, Afferent / drug effects*
  • Neurons, Afferent / physiology
  • Neurotoxins / pharmacology
  • Nociceptors / drug effects*
  • Phosphatidylinositol Diacylglycerol-Lyase
  • Phosphodiesterase Inhibitors / pharmacology
  • Pyrrolidinones / pharmacology
  • Receptors, Neurokinin-1 / drug effects*
  • Receptors, Neurokinin-1 / physiology
  • Reflex / drug effects
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology
  • Substance P / pharmacology*
  • Tetrodotoxin / pharmacology
  • Type C Phospholipases / antagonists & inhibitors

Substances

  • Biphenyl Compounds
  • Estrenes
  • Neurotoxins
  • Phosphodiesterase Inhibitors
  • Pyrrolidinones
  • Receptors, Neurokinin-1
  • 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
  • Substance P
  • Tetrodotoxin
  • Egtazic Acid
  • Inositol 1,4,5-Trisphosphate
  • Type C Phospholipases
  • GTP-Binding Proteins
  • Phosphatidylinositol Diacylglycerol-Lyase
  • CP 96345