Involvement of spinal tyrosine kinase in inflammatory and N-methyl-D-aspartate-induced hyperalgesia in rats.

Abstract

Phosphorylation of a subunit of N-methyl-D-aspartate (NMDA) receptor by protein tyrosine kinase (PTK) Src or Trk is known to enhance its channel activity. We examined whether a spinally administered selective PTK inhibitor, lavendustin A, which has high affinity for Src and Trk tyrosine kinases, could influence the development and maintenance of inflammatory hyperalgesia or NMDA-induced hyperalgesia. Inflammation was induced by injection of a mixture of carrageenan and kaolin into the tail base of rats. In another group of rats, hyperalgesia was induced by intrathecal administration of NMDA. Intrathecal administration of lavendustin A (1.0 microg) or NMDA receptor antagonist, (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cycloheptane-5,10-iminemaleate, MK-801 (3.0 microg) before injection of a mixture of carrageenan and kaolin or after the development of inflammation inhibited carrageenan-kaolin-induced mechanical hyperalgesia. Intrathecal injection of 1.0 microg NMDA produced thermal and mechanical hyperalgesia. Co-administration of 1.0 microg lavendustin A with NMDA significantly reduced the duration of spontaneous pain behaviour and inhibited NMDA-induced hyperalgesia. Lavendustin A itself did not cause any sedation, motor impairment or analgesia. Our results suggest that inhibition of PTK could be therapeutically effective as an analgesic in some NMDA receptor-mediated hyperalgesic states.

• Authors: Eiru Sato, Yoshito Takano, Yuichiro Kuno, Manami Takano, Isao Sato
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 468 Issue 3 Pg. 191-8 (May 16 2003) ISSN: 0014-2999 [Print] Netherlands
• PMID: 12754057 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Phenols
• Receptors, N-Methyl-D-Aspartate
• Kaolin
• lavendustin A
• N-Methylaspartate
• Dizocilpine Maleate
• Carrageenan
• Protein-Tyrosine Kinases

Topics

• Animals
• Carrageenan (administration & dosage, adverse effects)
• Dizocilpine Maleate (administration & dosage, pharmacology)
• Hot Temperature
• Hyperalgesia (chemically induced, complications, prevention & control)
• Inflammation (chemically induced, complications, prevention & control)
• Injections, Spinal
• Kaolin (administration & dosage, adverse effects)
• Male
• N-Methylaspartate (administration & dosage, adverse effects)
• Pain
• Pain Measurement
• Phenols (administration & dosage, pharmacokinetics)
• Protein-Tyrosine Kinases (administration & dosage, adverse effects, genetics)
• Rats
• Rats, Sprague-Dawley
• Receptors, N-Methyl-D-Aspartate (drug effects)
• Spinal Cord (drug effects, enzymology)