Inhalation of Cedrus atlantica essential oil alleviates pain behavior through activation of descending pain modulation pathways in a mouse model of postoperative pain

J Ethnopharmacol. 2015 Dec 4;175:30-8. doi: 10.1016/j.jep.2015.08.048. Epub 2015 Sep 4.


Ethnopharmacological relevance: Cedrus atlantica essential oil (CaEO) presents analgesic and anti-inflammatory sedative properties. However, it remains unknown whether CaEO alleviates acute postoperative pain.

Materials and methods: Here, we investigated the effect of CaEO on postoperative pain and its mechanisms related to the descending pain control in Swiss males mice induced by a plantar incision surgery (PIS) in the hindpaw.

Results: Inhalation of CaEO (5', 30' or 60') markedly reduced mechanical hypersensitivity. This effect was prevented by pre-treatment with naloxone or p-chlorophenylalanine methyl ester (PCPA, 100mg/kg, i.p.)-induced depletion of serotonin. In addition, p-alpha-methyl-para-tyrosin (AMPT, 100mg/kg, i.p.)-induced depletion of norepinephrine, intraperitoneal injection of the α2-adrenergic receptor antagonist yohimbine (0.15 mg/kg, i.p.) or haloperidol (1mg/kg, i.p.) an antagonist of dopaminergic (D1 and D2) receptors prevented the effect of CaEO on hypersensitivity.

Conclusions: These findings suggest that CaEO alleviates postoperative pain by activating the descending pain modulation pathways on the opioidergic, serotonergic, noradrenergic (α2-adrenergic) and dopaminergic (dopamine D1 and D2 receptors) systems.

Keywords: Aromatherapy; Ethnopharmacology; Incisional Pain; Mice; Surgery.

MeSH terms

  • Administration, Inhalation
  • Adrenergic alpha-2 Receptor Antagonists / pharmacology
  • Analgesics / administration & dosage
  • Analgesics / therapeutic use*
  • Animals
  • Behavior, Animal / drug effects
  • Cedrus*
  • Disease Models, Animal
  • Dopamine Antagonists / pharmacology
  • Fenclonine / analogs & derivatives
  • Fenclonine / pharmacology
  • Foot / surgery
  • Haloperidol / pharmacology
  • Hyperalgesia / drug therapy*
  • Hyperalgesia / metabolism
  • Male
  • Mice
  • Motor Activity / drug effects
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Oils, Volatile / administration & dosage
  • Oils, Volatile / therapeutic use*
  • Pain, Postoperative / drug therapy*
  • Pain, Postoperative / metabolism
  • Phytotherapy
  • Serotonin Antagonists / pharmacology
  • Yohimbine / pharmacology
  • alpha-Methyltyrosine / pharmacology


  • Adrenergic alpha-2 Receptor Antagonists
  • Analgesics
  • Dopamine Antagonists
  • Narcotic Antagonists
  • Oils, Volatile
  • Serotonin Antagonists
  • 4-chlorophenylalanine methyl ester
  • Yohimbine
  • Naloxone
  • alpha-Methyltyrosine
  • Haloperidol
  • Fenclonine