Intrathecal clonidine inhibits mechanical allodynia via activation of the spinal muscarinic M1 receptor in streptozotocin-induced diabetic mice

• Published in: European journal of pharmacology Vol. 505; no. 1-3; pp. 75 - 82
• Main Authors: KOGA, Kohei, HONDA, Kenji, ANDO, Sugum, HARASAWA, Ichiro, KAMIYA, Hiro-O, TAKANO, Yukio
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 28.11.2004
• Subjects: (4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride - pharmacology; Analgesics - administration & dosage; Analgesics - pharmacology; Animals; Atropine - pharmacology; Biological and medical sciences; Blood Glucose - drug effects; Blood Glucose - metabolism; Clonidine - administration & dosage; Clonidine - pharmacology; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - physiopathology; Diamines - pharmacology; Injections, Spinal; Male; Medical sciences; Mice; Motor Activity - drug effects; Muscarinic Agonists - pharmacology; Muscarinic Antagonists - pharmacology; Pain - etiology; Pain - prevention & control; Pain Threshold - drug effects; Pharmacology. Drug treatments; Piperidines - pharmacology; Pirenzepine - pharmacology; Receptor, Muscarinic M1 - agonists; Receptor, Muscarinic M1 - antagonists & inhibitors; Receptor, Muscarinic M1 - metabolism; Receptor, Muscarinic M2 - antagonists & inhibitors; Receptor, Muscarinic M3 - antagonists & inhibitors; Spinal Cord - drug effects; Spinal Cord - metabolism; Spinal Cord - physiopathology; Streptozocin - administration & dosage; Stress, Mechanical; Time Factors; Endocrinopathy; α2-Adrenergic receptor; Allodynia; Antineoplastic agent; Imidazole derivatives; Agonist; Spinal cord; α2-Adrenoreceptor; Diabetes mellitus; Rodentia; Intrathecal administration; M1 Muscarinic receptor; Cholinergic receptor; Vertebrata; Antibiotic; Mammalia; Mouse; Animal; Antihypertensive agent; α-Adrenergic receptor agonist; Clonidine; Muscarinic receptor; Diabetes; Streptozotocin
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2004.10.033

We examined the involvement of the spinal muscarinic receptors in the clonidine-induced antiallodynic effects. Mechanical sensitivity was assessed by stimulating the hind paw with von Frey filaments. In streptozotocin-treated (200 mg/kg, i.v.) diabetic mice, hypersensitivity to mechanical stimulation appeared 3 days after streptozotocin administration, and persisted for 11 days. This mechanical hypersensitivity (allodynia) was inhibited by the intrathecal (i.t.) injection of clonidine. The muscarinic receptor antagonist atropine (i.t.) and alpha2-adrenoreceptor antagonist yohimbine (i.t. or subcutaneous injection) abolished the antiallodynic effect of clonidine. The effect was mimicked by the muscarinic M1 receptor antagonist pirenzepine, but not by the muscarinic M2 receptor antagonist methoctoramine or the muscarinic M3 receptor antagonist 4-DAMP (4-diphenyl-acetoxy-N-methylpiperidine methiodide). In addition, the mechanical hypersensitivity in diabetic mice was reduced by the selective muscarinic M1 receptor agonist McN-A-343 (4-(m-chlorophenyl-carbamoyloxy)-2-butynyltrimethylammonium chloride) (i.t.). These results suggest that spinal muscarinic M1 receptors participate in the antiallodynic effect of clonidine in diabetic mice.