Korean J Physiol Pharmacol.  2006 Oct;10(5):255-261.

Calcium Ions are Involved in Modulation of Melittin-induced Nociception in Rat: I. Effect of Voltage-gated Calcium Channel Antagonist

• Shin HK
• Le KH

Abstract

Melittin-induced nociceptive responses are mediated by selective activation of capsaicin-sensitive primary afferent fibers and are modulated by excitatory amino acid receptor, cyclooxygenase, protein kinase C and serotonin receptor. The present study was undertaken to investigate the peripheral and spinal actions of voltage-gated calcium channel antagonists on melittin-induced nociceptive responses. Changes in mechanical threshold and number of flinchings were measured after intraplantar (i.pl.) injection of melittin (30microg/paw) into mid-plantar area of hindpaw. L-type calcium channel antagonists, verapamil [intrathecal (i.t.), 6 or 12microg; i.pl.,100 & 200microg; i.p., 10 or 30 mg], N-type calcium channel blocker, omega-conotoxin GVIA (i.t., 0.1 or 0.5microg; i.pl., 5microg) and P-type calcium channel antagonist, omega-agatoxin IVA (i.t., 0.5microg; i.pl., 5microg) were administered 20 min before or 60 min after i.pl. injection of melittin. Intraplantar pre-treatment and i.t. pre- or post-treatment of verapamil and omega-conotoxin GVIA dose-dependently attenuated the reduction of mechanical threshold, and melittin-induced flinchings were inhibited by i.pl. or i.t. pre-treatment of both antagonists. P-type calcium channel blocker, omega-agatoxin IVA, had significant inhibitory action on flinching behaviors, but had a limited effect on melittin-induced decrease in mechanical threshold. These experimental findings suggest that verapamil and omega-conotoxin GVIA can inhibit the development and maintenance of melittin-induced nociceptive responses.

Keyword

Melittin; Hyperalgesia; Spontaneous pain; Voltage-gated calcium channel antagonist

MeSH Terms

Animals
Calcium Channels*
Calcium Channels, L-Type
Calcium Channels, N-Type
Calcium Channels, P-Type
Calcium*
Hyperalgesia
Ions*
Melitten
Nociception*
omega-Agatoxin IVA
omega-Conotoxin GVIA
Prostaglandin-Endoperoxide Synthases
Protein Kinase C
Rats*
Receptors, Glutamate
Serotonin
Verapamil
Calcium
Calcium Channels
Calcium Channels, L-Type
Calcium Channels, N-Type
Calcium Channels, P-Type
Ions
Melitten
Prostaglandin-Endoperoxide Synthases
Protein Kinase C
Receptors, Glutamate
Serotonin
Verapamil
omega-Agatoxin IVA
omega-Conotoxin GVIA