Dynorphin A increases substance P release from trigeminal primary afferent C-fibers.
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.
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Related Subject Headings
- Trigeminal Nuclei
- Substance P
- Receptors, N-Methyl-D-Aspartate
- Rats, Sprague-Dawley
- Rats
- Pharmacology & Pharmacy
- Neurons, Afferent
- Nerve Fibers
- Narcotic Antagonists
- Naltrexone
Citation
Published In
DOI
EISSN
ISSN
Publication Date
Volume
Issue
Start / End Page
Related Subject Headings
- Trigeminal Nuclei
- Substance P
- Receptors, N-Methyl-D-Aspartate
- Rats, Sprague-Dawley
- Rats
- Pharmacology & Pharmacy
- Neurons, Afferent
- Nerve Fibers
- Narcotic Antagonists
- Naltrexone