Dynorphin A increases substance P release from trigeminal primary afferent C-fibers

Eur J Pharmacol. 1999 Jan 29;366(1):27-34. doi: 10.1016/s0014-2999(98)00897-8.

Abstract

Dynorphin A-(1-17) has been found to produce spinal antianalgesia and allodynia. Thus, we studied whether dynorphin A-(1-17) modulates substance P release evoked by the C-fiber-selective stimulant capsaicin (1 microM) from trigeminal nucleus caudalis slices. Very low concentrations of dynorphin A-(1-17) (0.01-0.1 nM) strongly facilitated capsaicin-evoked substance P release. This dynorphin A-(1-17) effect was not blocked by the opioid receptor antagonists naloxone (100 nM), beta-funaltrexamine (20 nM), naloxonazine (1 nM), nor-binaltorphimine (3 nM) and ICI 174,864 (N,N-dialyl-Tyr-Aib-Phe-Leu; 0.3 microM). Yet, the effect of dynorphin A-(1-17) was blocked by the NMDA receptor antagonist MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5-10-imine maleate; 0.3 microM). Neonatal treatment with capsaicin (50 mg/kg s.c.), which destroys substance P-containing primary afferents, abolished the excitatory effect of dynorphin A-(1-17) on K+-evoked substance P release. In conclusion, dynorphin A-(1-17) increases substance P release from C-fibers by the activation of NMDA receptors which supports the involvement of presynaptic mechanisms in dynorphin-induced antianalgesia and allodynia.

MeSH terms

  • Animals
  • Animals, Newborn
  • Capsaicin / pharmacology
  • Dizocilpine Maleate / pharmacology
  • Dynorphins / pharmacology*
  • Enkephalin, Leucine / analogs & derivatives
  • Enkephalin, Leucine / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • In Vitro Techniques
  • Male
  • Naloxone / analogs & derivatives
  • Naloxone / pharmacology
  • Naltrexone / analogs & derivatives
  • Naltrexone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Nerve Fibers / drug effects*
  • Nerve Fibers / metabolism
  • Neurons, Afferent / drug effects*
  • Neurons, Afferent / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Substance P / drug effects*
  • Substance P / metabolism
  • Trigeminal Nuclei / drug effects*
  • Trigeminal Nuclei / metabolism

Substances

  • Excitatory Amino Acid Antagonists
  • Narcotic Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Substance P
  • Naloxone
  • norbinaltorphimine
  • Enkephalin, Leucine
  • Naltrexone
  • Dizocilpine Maleate
  • beta-funaltrexamine
  • Dynorphins
  • naloxonazine
  • N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine
  • Capsaicin