Medullary N-type and P/Q-type calcium channels contribute to neuropathy-induced allodynia.
The present study was designed to determine the contribution of N-type, P/Q-type and L-type calcium channels in the rostral ventromedial medulla to tactile allodynia following peripheral nerve injury. L5/L6 spinal nerve ligation in rats produced tactile allodynia, which was dose-dependently inhibited by intrarostral ventromedial medulla microinjection of the N-type calcium channel antagonist omega-conotoxin MVIIA. Similarly, intrarostral ventromedial medulla microinjection of the P/Q-type calcium channel antagonist omega-agatoxin IVA inhibited spinal nerve ligation-induced tactile allodynia, whereas intrarostral ventromedial medulla microinjection of the L-type calcium channel antagonist nimodipine had no effect. These results demonstrate that N-type and P/Q-type calcium channels in the rostral ventromedial medulla contribute to tactile allodynia following peripheral neuropathy, likely via neurotransmitter-mediated activation of descending facilitatory systems from the rostral ventromedial medulla.
Urban
Mark O
MO
Department of Pharmacology, Merck Research Laboratories, San Diego, CA 92121, USA. mark.urban@merck.com
Ren
Kunkun
K
Sablad
Marciano
M
Park
Kenneth T
KT
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000502:physiology*; D006930:Hyperalgesia / Q000503:physiopathology; D008026:Ligation; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology*; D008845:Microinjections; D009437:Neuralgia / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves / Q000502:physiology; D014110:Touch; D020867:omega-Agatoxin IVA / Q000494:pharmacology; D020960:omega-Conotoxins / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins; C078452:ziconotide