Abstract |
Male Sprague-Dawley rats were used to evaluate the antinociceptive properties of the selective N-type voltage-sensitive calcium channel (VSCC) blocker, SNX-111, when the compound is administered spinally by either bolus injection or continuous, constant-rate infusion into the subarachnoid space. SNX-111 produced significant, dose-dependent antinociceptive effects by suppressing both the acute (phase 1: ED50, 14 ng/hr) and tonic (phase 2: ED50, 0.82 ng/hr) phases of the formalin test when it was infused for 72 hr immediately before testing. Phase 2 nociceptive responses were suppressed by bolus injections of 100 ng SNX-111. SNX-111 was approximately 1000-fold more potent than morphine in blocking phase 2 responses when the compounds were administered by intrathecal bolus injection. In rats with an experimentally induced painful peripheral neuropathy, intrathecal bolus injections of 30 to 300 ng SNX-111 blocked mechanical allodynia in a dose-dependent manner. Subacute administration of SNX-111 (1, 10 and 100 ng/hr) by continuous intrathecal infusion produced a reversible blockade of mechanical allodynia without apparent development of tolerance. These results show that: 1) selective N-type VSCC blockers are potent and efficacious antinociceptive agents when they are administered by the spinal route; 2) selective N-type VSCC blockers are effective in rat models of acute, persistent and neuropathic pain; and 3) N-type VSCCs play a significant role in the spinal processing of noxious somatosensory input.
|
Authors | S S Bowersox, T Gadbois, T Singh, M Pettus, Y X Wang, R R Luther |
Journal | The Journal of pharmacology and experimental therapeutics
(J Pharmacol Exp Ther)
Vol. 279
Issue 3
Pg. 1243-9
(Dec 1996)
ISSN: 0022-3565 [Print] United States |
PMID | 8968347
(Publication Type: Journal Article)
|
Chemical References |
- Analgesics
- Calcium Channel Blockers
- Peptides
- omega-Conotoxins
- Formaldehyde
- ziconotide
|
Topics |
- Analgesics
(pharmacology, therapeutic use)
- Animals
- Calcium Channel Blockers
(pharmacology, therapeutic use)
- Disease Models, Animal
- Formaldehyde
(toxicity)
- Ion Channel Gating
- Male
- Neurons
(metabolism)
- Pain
(chemically induced, drug therapy)
- Peptides
(pharmacology, therapeutic use)
- Peripheral Nervous System Diseases
(chemically induced, drug therapy)
- Rats
- Rats, Sprague-Dawley
- Spinal Cord
(drug effects, metabolism, physiopathology)
- omega-Conotoxins
|