Title : Intrathecal neostigmine reduces the zymosan-induced inflammatory response in a mouse air pouch model via adrenomedullary activity: involvement of spinal muscarinic type 2 receptors - Yoon_2005_Neuropharmacol_49_275 |
Author(s) : Yoon SY , Kwon YB , Kim HW , Roh DH , Kang SY , Kim CY , Han HJ , Kim KW , Yang IS , Beitz AJ , Lee JH |
Ref : Neuropharmacology , 49 :275 , 2005 |
Abstract :
Intrathecal (IT) injection of neostigmine (a cholinesterase inhibitor) has been reported to produce a significant anti-nociceptive effect in a number of inflammatory pain models. However, a potential anti-inflammatory effect of IT neostigmine in these models has not been investigated. In the present study, we have examined the 'anti-inflammatory effect of IT injection of neostigmine' (AI-NEO) using a standard mouse air pouch model by evaluating the effect of AI-NEO on zymosan-induced leukocyte migration and myeloperoxidase (MPO) release. IT neostigmine was found to suppress both leukocyte migration and MPO degranulation in a dose dependent manner. We then established which subtypes of cholinergic receptors were involved in this AI-NEO. IT pretreatment with atropine (a muscarinic receptor antagonist) but not hexamethonium (a nicotinic receptor antagonist) completely blocked the IT neostigmine anti-inflammatory effect. Subsequent experiments showed that IT pretreatment with methoctramine (a muscarinic type 2 (M2) receptor antagonist), but not pirenzepine (M1 receptor antagonist) or 4-DAMP (M3 receptor antagonist), suppressed the AI-NEO. We then evaluated whether adrenal glandular activity was important in the AI-NEO. Adrenalectomy significantly blocked the AI-NEO, while intraperitoneal pretreatment with the beta-adrenoceptor antagonist (propranolol), but not the corticosteroid antagonist (RU486) reversed AI-NEO. In conclusion, these results indicate that IT neostigmine facilitates the activation of spinal M2 receptors and this activation ultimately leads to release of adrenal catecholamines which contribute to the anti-inflammatory effect observed at the site of tissue inflammation. |
PubMedSearch : Yoon_2005_Neuropharmacol_49_275 |
PubMedID: 15922370 |
Inhibitor | Methoctramine |
Yoon SY, Kwon YB, Kim HW, Roh DH, Kang SY, Kim CY, Han HJ, Kim KW, Yang IS, Beitz AJ, Lee JH (2005)
Intrathecal neostigmine reduces the zymosan-induced inflammatory response in a mouse air pouch model via adrenomedullary activity: involvement of spinal muscarinic type 2 receptors
Neuropharmacology
49 :275
Yoon SY, Kwon YB, Kim HW, Roh DH, Kang SY, Kim CY, Han HJ, Kim KW, Yang IS, Beitz AJ, Lee JH (2005)
Neuropharmacology
49 :275