Dynorphin A increases substance P release from trigeminal primary afferentC-fibers

Dynorphin A-(1-17) has been found to produce spinal antianalgesia and allod ynia. Thus, we studied whether dynorphin A-(1-17) modulates substance P rel ease evoked by the C-fiber-selective stimulant capsaicin (1 mu M) from trig eminal nucleus caudalis slices. Very low concentrations of dynorphin A-(1-1 7) (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 anta gonists 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 mu M). Yet, the effect of dynorphin A-(1-17) was blocked by the NMDA r eceptor antagonist MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclo hepten-5-10-imine maleate; 0.3 mu M) Neonatal treatment with capsaicin (50 mg/kg s.c.), which destroys substance P-containing primary afferents, aboli shed the excitatory effect of dynorphin A-(1-17) on K+-evoked substance P r elease. In conclusion, dynorphin A-(1-17) increases substance P release fro m C-fibers by the activation of NMDA receptors which supports the involveme nt of presynaptic mechanisms in dynorphin-induced antianalgesia and allodyn ia. (C) 1999 Elsevier Science B.V. All rights reserved.