Antinociceptive activity of the monoterpene α-phellandrene in rodents: possible mechanisms of action.
OBJECTIVE
The aim of this work was to investigate the antinociceptive property of α-phellandrene (α-PHE) in experimental nociception models and possible mechanisms involved.


METHODS
Mass spectrometry was used to evaluate the purity and molecular mass of α-PHE. Macrophages from mice peritoneal cavity were used in an MTT test. Rodents were used in tests of chemical and mechanical nociception. In the study of the mechanisms, the animals were treated with pharmacological tools and then submitted to the glutamate test.


RESULTS
α-PHE purity was 98.2% and molecular mass 136.1 Da. α-PHE did not show cytotoxicity. In the writhing and capsaicin tests, α-PHE promoted the antinociceptive effect in all evaluated doses (minimum dose 3.125 mg/kg). In the formalin test, α-PHE (50 mg/kg) was effective in inhibiting both phases. In the glutamate test, the monoterpene (12.5 mg/kg) decreased the nociceptive response. In carrageenan-induced hyperalgesia, α-PHE (50 mg/kg) decreased the hypernociception index. In the study of the mechanisms involved, pretreatment with naloxone reversed the α-PHE antinociceptive effect, the same occurred with glibenclamide, l-arginine, atropine and yohimbine. α-PHE did not show muscle relaxant activity or central depressant effects in open field and rota rod tests.


CONCLUSIONS
α-PHE has an antinociceptive effect and it possibly involves the glutamatergic, opioid, nitrergic, cholinergic and adrenergic systems.
Medicinal Plants Research Center, Federal University of Piauí, Parnaíba, Piauí Department of Chemistry, Federal University of Sergipe, Aracajú, Sergipe, Brazil.
David F
DF
Lima
Marcela S
MS
Brandão
Joelma B
JB
Moura
Joseana M R S
JM
Leitão
Fernando A A
FA
Carvalho
Leiz M C V
LM
Miúra
José R S A
JR
Leite
Damião P
DP
Sousa
Fernanda R C
FR
Almeida
D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000081005:Cyclohexane Monoterpenes; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D039821:Monoterpenes / Q000737:chemistry / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D009822:Oils, Volatile / Q000737:chemistry / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D051381:Rats; D017208:Rats, Wistar
D000700:Analgesics; D000081005:Cyclohexane Monoterpenes; D039821:Monoterpenes; D009822:Oils, Volatile; C005403:alpha phellandrene