Intrathecal clonidine inhibits mechanical allodynia via activation of the spinal muscarinic M1 receptor in streptozotocin-induced diabetic mice.
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.
Koga
Kohei
K
Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan.
Honda
Kenji
K
Ando
Suguru
S
Harasawa
Ichiro
I
Kamiya
Hiro-o
HO
Takano
Yukio
Y
D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / Q000494:pharmacology; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D003959:Diamines / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010146:Pain / Q000209:etiology / Q000517:prevention & control*; D017288:Pain Threshold / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D043643:Receptor, Muscarinic M1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D043585:Receptor, Muscarinic M2 / Q000037:antagonists & inhibitors; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D013311:Streptozocin / Q000008:administration & dosage; D013314:Stress, Mechanical; D013997:Time Factors
D000700:Analgesics; D001786:Blood Glucose; D003959:Diamines; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D010880:Piperidines; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D010890:Pirenzepine; D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride; D013311:Streptozocin; D001285:Atropine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D003000:Clonidine; C054938:methoctramine