title: Agmatine attenuates neuropathic pain in rats: possible mediation of nitric oxide and noradrenergic activity in the brainstem and cerebellum.
abstract: Effect of agmatine (10-400 mg/kg) on neuropathic pain in a rat model produced by loose ligatures around the common sciatic nerve was studied. The involvement of possible alterations in nitric oxide (NO) levels [measured as its stable metabolites nitrate + nitrite] and in noradrenergic activity [measured as norepinephrine and 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) levels] in this effect was also investigated biochemically in the brainstem and cerebellum. Agmatine increased the neuropathic pain threshold at 300 and 400 mg/kg. There was almost a twofold increase in nitrate + nitrite levels in the brainstem and cerebellum of the rats with neuropathic pain and agmatine decreased the high nitrate + nitrite levels only in the brainstem at 300 mg/kg and both in the brainstem and cerebellum at 400 mg/kg. Ligation of sciatic nerve resulted in almost twofold increase in norepinephrine and MHPG levels only in the brainstem of the rats. Agmatine decreased MHPG levels at 300 and 400 mg/kg, however it decreased norepinephrine levels only at the higher dose. These findings indicate that agmatine decreases neuropathic pain, an effect which may involve the reduction of NO levels and noradrenergic activity in the brain.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Ege University 35100, Izmir, Turkey. aytul@med.ege.edu.tr
authors.forename: Aytül
authors.initials: A
authors.lastname: Onal
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Delen
authors.forename: Sibel
authors.initials: S
authors.lastname: Ulker
authors.forename: Necdet
authors.initials: N
authors.lastname: Soykan
mesh_terms: D000376:Agmatine / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D010146:Pain / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011941:Receptors, Adrenergic / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000700:Analgesics; D011941:Receptors, Adrenergic; D009569:Nitric Oxide; D008734:Methoxyhydroxyphenylglycol; D000376:Agmatine; D009638:Norepinephrine