title: Analgesic activity of piracetam: effect on cytokine production and oxidative stress.
abstract: Piracetam is a prototype of nootropic drugs used to improve cognitive impairment. However, recent studies suggest that piracetam can have analgesic and anti-inflammatory effects. Inflammatory pain is the result of a process that depends on neutrophil migration, cytokines and prostanoids release and oxidative stress. We analyze whether piracetam has anti-nociceptive effects and its mechanisms. Per oral pretreatment with piracetam reduced in a dose-dependent manner the overt pain-like behavior induced by acetic acid, phenyl-p-benzoquinone, formalin and complete Freund's adjuvant. Piracetam also diminished carrageenin-induced mechanical and thermal hyperalgesia, myeloperoxidase activity, and TNF-α-induced mechanical hyperalgesia. Piracetam presented analgesic effects as post-treatment and local paw treatment. The analgesic mechanisms of piracetam were related to inhibition of carrageenin- and TNF-α-induced production of IL-1β as well as prevention of carrageenin-induced decrease of reduced glutathione, ferric reducing ability and free radical scavenging ability in the paw. These results demonstrate that piracetam presents analgesic activity upon a variety of inflammatory stimuli by a mechanism dependent on inhibition of cytokine production and oxidative stress. Considering its safety and clinical use for cognitive function, it is possible that piracetam represents a novel perspective of analgesic.
authors.affiliation: Departamento de Patologia, Universidade Estadual de Londrina, PR, Brazil.
authors.forename: Suelen A
authors.initials: SA
authors.lastname: Navarro
authors.forename: Karla G G
authors.initials: KG
authors.lastname: Serafim
authors.forename: Sandra S
authors.initials: SS
authors.lastname: Mizokami
authors.forename: Miriam S N
authors.initials: MS
authors.lastname: Hohmann
authors.forename: Rubia
authors.initials: R
authors.lastname: Casagrande
authors.forename: Waldiceu A
authors.initials: WA
authors.lastname: Verri
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D010146:Pain / Q000517:prevention & control; D010889:Piracetam / Q000494:pharmacology*
chemical_list: D000700:Analgesics; D016207:Cytokines; D010889:Piracetam