Yoon_2005_Neuropharmacol_49_275

Reference

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

Related information

Inhibitor Methoctramine

Citations formats

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