The noradrenergic component contributing to spinal fentanyl-induced antinociception is supraspinally mediated.
Adrenergic Antagonists; Analgesics/*pharmacology; Animals; Fentanyl/*pharmacology; Injections; Intraventricular; Male; Methysergide/pharmacology; Naltrexone/pharmacology; Norepinephrine/*physiology; Pain Measurement/drug effects; Phentolamine/pharmacology; Rats; Reaction Time/drug effects; Serotonin Antagonists; Spinal; Spinal Cord/*physiology; Sprague-Dawley
1. Male Sprague-Dawley rats were fitted with intrathecal (i.t.) and intracerebroventricular (i.c.v.) catheters. Fentanyl was injected either i.t. or i.c.v., and the antinociceptive efficacy of fentanyl was evaluated using the tail-flick analgesiometric assay. 2. Fentanyl dose-dependently elevated tail-flick latency (TFL) following i.c.v. or i.t. administration. The antinociceptive effects of fentanyl were reversed by naltrexone. 3. Experiments were also designed to evaluate the effects of serotonin and alpha-adrenoceptor antagonists on i.t. or i.c.v. fentanyl-induced elevations in TFL. 4. Phentolamine administered i.t. reversed both the spinal and supraspinal antinociceptive effects of fentanyl, whereas i.t. methysergide did not significantly alter the i.t. or i.c.v. effects of the mu agonist. 5. These data suggest that fentanyl-induced antinociception does not rely on local serotonergic neuronal activation. Due to the highly lipophilic nature of fentanyl, it is possible that the noradrenergic component contributing to spinal fentanyl-induced analgesia is supraspinally-mediated.
Crisp T; Stafinsky J L; Perni V C; Uram M
General pharmacology
1992
1992-11
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0306-3623(92)90291-q" target="_blank" rel="noreferrer noopener">10.1016/0306-3623(92)90291-q</a>
Serotonin contributes to the spinal antinociceptive effects of morphine.
Adrenergic alpha-Antagonists/pharmacology; Adrenergic Antagonists; Analgesics/*pharmacology; Animals; Biogenic Monoamines/physiology; Dose-Response Relationship; Drug; Inbred Strains; Injections; Male; Morphine/*pharmacology; Naltrexone/pharmacology; Nerve Endings/drug effects; Opioid/drug effects; Rats; Reaction Time; Receptors; Serotonin Antagonists/pharmacology; Serotonin/*physiology; Spinal; Spinal Cord/*drug effects
This study was designed to determine if morphine administered intrathecally (IT) interacts with serotonergic or noradrenergic nerve terminals in the spinal cord to produce analgesia on the spinally mediated tail-flick test. Male Sprague-Dawley rats were fitted with IT catheters. One week later, animals were spinally pretreated with receptor antagonists selective for opioid, serotonin or alpha-adrenoceptors, and the ability of these agents to alter spinal morphine-induced antinociception was assessed. Morphine dose-dependently elevated tail-flick latency in a naltrexone-reversible manner. The serotonin receptor antagonists spiroxatrine (5-HT1A), pindolol (5-HT1B), ritanserin (5-HT2) and ICS
Crisp T; Stafinsky J L; Uram M; Perni V C; Weaver M F; Spanos L J
Pharmacology, biochemistry, and behavior
1991
1991-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0091-3057(91)90133-m" target="_blank" rel="noreferrer noopener">10.1016/0091-3057(91)90133-m</a>