Blockade of spinal N- and P-type, but not L-type, calcium channels inhibits the excitability of rat dorsal horn neurones produced by subcutaneous formalin inflammation.
The effects of the intrathecal (i.t.) administration of different voltage-sensitive calcium channel (VSCC) blockers were studied in the formalin model of inflammation. The responses of convergent dorsal horn neurones after the subcutaneous injection of formalin (5% formaldehyde, 50 microliters volume) were recorded extracellularly in rats under halothane anaesthesia. Administration of the L-type calcium channel blocker verapamil, 5 and 50 micrograms, before formalin injection had no effect on either the first or second phase of the formalin response. Pre-treatment with the N-type calcium channel blocker omega-Conotoxin-GVIA, 0.1 and 0.4 microgram, reduced both phases of the formalin response. The low dose of omega-Conotoxin-GVIA significantly inhibited the first phase response whereas the high dose significantly reduced the second phase. Pre-treatment with the P-type calcium channel blocker omega-Agatoxin-IVA, 0.125 and 0.5 microgram, did not cause a significant inhibition of the first phase whereas a marked dose-related reduction in the second phase of formalin response was found with the high dose producing 95% inhibition. These results demonstrate that spinal N- and P-type, but not L-type, VSCCs are involved in the inflammation-evoked hyperexcitability of dorsal horn neurones after peripheral formalin injection. Since selective antagonists for each type of VSCC had differential effects on the formalin response, it is suggested that each type of VSCC could be preferentially regulating or coupled to the release of certain neurotransmitters in the enhanced nociceptive transmission at the spinal level following formalin inflammation.
Diaz
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Department of Pharmacology, University College London, UK.
Dickenson
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AH
D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D004594:Electrophysiology; D005557:Formaldehyde / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007278:Injections, Spinal; D007279:Injections, Subcutaneous; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013111:Spider Venoms / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology; D020867:omega-Agatoxin IVA
D002121:Calcium Channel Blockers; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D005557:Formaldehyde; D014700:Verapamil