TitleAnalgesic and antiallodynic effects of antidepressants after infiltration into the rat.
Publication TypeJournal Article
Year of Publication2010
AuthorsGarcia X, del Valle J, Escribano E, Domenech J, Queralt J
Date Publishedjan
KeywordsAdrenergic Uptake Inhibitors, Adrenergic Uptake Inhibitors: administration & dos, Adrenergic Uptake Inhibitors: pharmacology, Analgesics, Analgesics: administration & dosage, Analgesics: pharmacology, Anesthetics, Animal, Animals, Antidepressive Agents, Bupivacaine, Bupivacaine: pharmacology, Disease Models, Dose-Response Relationship, Drug, Hyperalgesia, Hyperalgesia: drug therapy, Local, Local: pharmacology, Male, Pain, Pain: drug therapy, Rats, Sciatic Neuropathy, Sciatic Neuropathy: drug therapy, Serotonin Uptake Inhibitors, Serotonin Uptake Inhibitors: administration & dosa, Serotonin Uptake Inhibitors: pharmacology, Sprague-Dawley, Time Factors, Tricyclic, Tricyclic: administration &, Tricyclic: pharmacology
AbstractTricyclic antidepressants (TCA) have potent local anesthetic properties and may produce a long-lasting pain blockade that could be of interest in relieving chronic pain states such as neuropathic pain, but there are only few data comparing their dose-response curves of analgesic activity under the same experimental conditions. This study examines the time course of pain-relieving properties of 7 TCA in heat-induced paw withdrawal after subcutaneous administration. Mixed inhibitors of norepinephrine and serotonin uptake (amitriptyline, nortriptyline, imipramine, desipramine, doxepin) and selective inhibitors of serotonin uptake (fluoxetine and fluvoxamine) were assayed. The TCA with the longest analgesic activity were selected to test its antiallodynic effect in the neuropathic pain model of chronic sciatic nerve constriction injury. Bupivacaine was used as a reference drug in both experiments. A dose versus time of maximal analgesic effect curve was constructed for each drug. The longest analgesic effect was obtained for doxepin and imipramine. Although low doses of amitriptyline showed the same activity than doxepin, higher doses failed to reach the same effect. Selective inhibitors of serotonin showed no action at all doses tested. In the chronic sciatic nerve constriction injury model, doxepin and, to a smaller degree, amitriptyline and imipramine protected from allodynia; bupivacaine was ineffective. The antiallodynic effect always lasted less long than the analgesic effect. These observations provide support for the potential use of TCA as durable analgesics. Doxepin overall showed the most outstanding results in pain relief.