Nerve growth factor- and neurotrophin-3-induced changes in nociceptive threshold and the release of substance P from the rat isolated spinal cord.

Abstract

Acute superfusion of nerve growth factor (NGF; 1-100 ng/ml) through a naive rat spinal cord preparation did not alter basal or electrically evoked release of substance P-like immunoreactivity (SP-LI). In contrast, neurotrophin-3 (NT-3; 1-100 ng/ml), although not modifying SP-LI basal outflow, dose-dependently inhibited the electrically evoked, but not capsaicin (10 nM)-induced, release of the peptide. This NT-3 (10 ng/ml)-induced inhibition persisted even in the presence of 100 ng/ml NGF in the perfusion fluid and was still significant when the evoked release of SP-LI was enhanced by a prolonged in vivo treatment with NGF. Co-superfusion with naloxone (0.1 microM), but not CGP 36742 (100 microM), a GABAB antagonist, prevented NT-3 (10 ng/ml) inhibition of SP-LI release. Basal and electrically evoked release of SP-LI from the rat spinal cord in vitro was not modified 24 hr after single systemic injection of either NGF (1 mg/kg) or NT-3 (10 mg/kg). At these time intervals from administration, NGF had induced thermal and mechanical hyperalgesia in the rat hindpaw, and NT-3 had induced mechanical, but not thermal, hypoalgesia. NT-3 administered six times over a 2 week period (at 1 mg/kg) did not alter thermal threshold but significantly reduced electrically evoked release of SP-LI from the spinal cord. An identical treatment regimen with 1 mg/kg NGF induced a significant increase in evoked release of SP-LI. However, this was not associated with a significant hyperalgesia. Although finding that NGF-induced hyperalgesia does not clearly correlate with changes in the release of SP-LI in the spinal cord, this study shows that NT-3 is an inhibitor of SP-LI release and suggests that this mechanism may be responsible for NT-3-induced antinociception.

• Authors: M Malcangio, N E Garrett, S Cruwys, D R Tomlinson
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 17 Issue 21 Pg. 8459-67 (Nov 01 1997) ISSN: 0270-6474 [Print] United States
• PMID: 9334418 (Publication Type: Journal Article)

Chemical References

• Analgesics
• GABA Antagonists
• GABA-B Receptor Antagonists
• Narcotic Antagonists
• Nerve Growth Factors
• Neurotrophin 3
• Organophosphorus Compounds
• (3-aminopropyl)(n-butyl)phosphinic acid
• Substance P
• Naloxone
• Capsaicin

Topics

• Analgesics (pharmacology)
• Animals
• Capsaicin (pharmacology)
• Dose-Response Relationship, Drug
• Drug Interactions
• Evoked Potentials (drug effects)
• GABA Antagonists (pharmacology)
• GABA-B Receptor Antagonists
• Hot Temperature
• Hyperalgesia (chemically induced, physiopathology)
• Hypesthesia (chemically induced, physiopathology)
• Injections, Subcutaneous
• Male
• Naloxone (pharmacology)
• Narcotic Antagonists (pharmacology)
• Nerve Growth Factors (administration & dosage, pharmacology, toxicity)
• Neurotrophin 3
• Organophosphorus Compounds (pharmacology)
• Pain (physiopathology)
• Pain Threshold (drug effects)
• Perfusion
• Pressure
• Rats
• Rats, Wistar
• Secretory Rate (drug effects)
• Single-Blind Method
• Spinal Cord (drug effects, metabolism)
• Substance P (metabolism)