Experimental conditions for the continuous subcutaneous infusion of four central analgesics in rats

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 2002-07, Vol.72 (4), p.943-951
• Main Authors: Bruins Slot, L.A, Tarayre, J.-P, Koek, W, Ribet, J.-P, Colpaert, F.C
• Format: Article
• Language: English
• Subjects: Acetates - administration & dosage; Acetates - pharmacology; Amines; Analgesics; Analgesics - administration & dosage; Analgesics - chemistry; Analgesics - therapeutic use; Anesthetics, Dissociative - administration & dosage; Anesthetics, Dissociative - pharmacology; Animals; Anticonvulsants - administration & dosage; Anticonvulsants - pharmacology; Antidepressive Agents, Tricyclic - pharmacology; Biological and medical sciences; Chromatography, High Pressure Liquid; Chronic Disease; Convulsants - pharmacology; Cyclohexanecarboxylic Acids; Drug Stability; Gabapentin; gamma-Aminobutyric Acid; Hypothermia - chemically induced; Hypothermia - prevention & control; Imipramine - pharmacology; Infusion Pumps, Implantable; Ketamine - administration & dosage; Ketamine - pharmacology; Male; Medical sciences; Morphine - pharmacology; Neuropharmacology; Osmotic mini-pumps; Pain - drug therapy; Pain Measurement - drug effects; Pentylenetetrazole - antagonists & inhibitors; Pentylenetetrazole - pharmacology; Pharmacological activity; Pharmacology. Drug treatments; Rat; Rats; Rats, Sprague-Dawley; Solubility; Subcutaneous continuous infusion; Tetrabenazine; Tolerability
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/S0091-3057(02)00760-8

For the analysis of pharmacotherapeutic regimens for chronic pain in animals, it is important to establish delivery methods in which analgesics can be administered continuously and at a constant rate for a prolonged period of time. This allows for the assessment of how drug effects may vary over time in the presence of ongoing pain. The present study determined, for four analgesic compounds, the maximal doses that met all of the following criteria: (i) water-soluble, (ii) stable over 14 days at 38 °C, and (iii) devoid of undesirable side-effects in normal rats, as assessed by evolution of body weight and temperature after the subcutaneous implantation of an osmotic mini-pump that continuously infused the compounds over a 14-day period. The results showed the maximal doses to be 5 mg/rat/day for morphine hydrochloride, 2.5 mg/rat/day for imipramine hydrochloride, 20 mg/rat/day for ketamine hydrochloride, and 10 mg/rat/day for gabapentin. These doses were further found to be sufficient to express each compound's representative pharmacological activity. The conditions identified here appear appropriate for future studies of these four compounds in rat models of chronic pain and neuropathic allodynia.