title: Anti-hypernociceptive properties of agmatine in persistent inflammatory and neuropathic models of pain in mice.
abstract: The present study examined the anti-hypernociceptive effects of agmatine (AGM) in acute and chronic models of behavioural pain in mice. Agmatine (30 mg/kg, i.p. 30 min early), produced time-dependent inhibition of mechanical hypernociception induced by Complete Freund's Adjuvant (CFA) injected in the mice paw (inhibition of 52+/-7%) after 4 h. Given chronically (twice a day) during 10 days, AGM significantly reversed the mechanical hypernociception caused by CFA (inhibition of 43+/-6% to 67+/-5%). Moreover, AGM also significantly reduced the mechanical hypernociception caused by partial sciatic nerve ligation (PSNL) during 6 h, with inhibition of 81+/-8%. In thermal hypernociception (cold stimuli) caused by PSNL the antinociceptive effect of AGM was prolonged by 4 h with inhibition of 97+/-3% observed 1 h after the treatment. Nevertheless, AGM failed to inhibit the paw oedema caused by CFA and the myeloperoxidase enzyme activity. Of note, AGM (10-100 mg/kg, i.p., 30 min before) also elicited a pronounced inhibition of the biting response induced by TNF-alpha and IL-1beta in mice, with mean ID(50) values of 61.3 mg/kg (47.7-78.6 mg/kg) and 30.4 mg/kg (18.6-49.8 mg/kg) and inhibitions of 75+/-5% and 66+/-6%, respectively. Together, present and previous findings show that AGM given systemically is effective in inhibiting mechanical and thermal hypernociception present in chronic inflammatory processes caused by CFA and also the neuropathic pain caused by PSNL.
authors.affiliation: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis, 88049-000, SC, Brazil.
authors.forename: Ana Flávia
authors.initials: AF
authors.lastname: Paszcuk
authors.forename: Vinicius M
authors.initials: VM
authors.lastname: Gadotti
authors.forename: Daiane
authors.initials: D
authors.lastname: Tibola
authors.forename: Nara L M
authors.initials: NL
authors.lastname: Quintão
authors.forename: Ana Lúcia S
authors.initials: AL
authors.lastname: Rodrigues
authors.forename: João B
authors.initials: JB
authors.lastname: Calixto
authors.forename: Adair R S
authors.initials: AR
authors.lastname: Santos
mesh_terms: D000376:Agmatine / Q000627:therapeutic use*; D000700:Analgesics / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004487:Edema / Q000209:etiology / Q000473:pathology; D005260:Female; D005620:Freund's Adjuvant; D007249:Inflammation / Q000139:chemically induced / Q000150:complications*; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology; D010146:Pain / Q000188:drug therapy* / Q000209:etiology*; D010147:Pain Measurement / Q000379:methods; D009195:Peroxidase / Q000378:metabolism; D020426:Sciatic Neuropathy / Q000150:complications*
chemical_list: D000700:Analgesics; D016207:Cytokines; D000376:Agmatine; D005620:Freund's Adjuvant; D009195:Peroxidase