Antihyperalgesic and antidepressive actions of (R)-(+)-limonene, α-phellandrene, and essential oil from Schinus terebinthifolius fruits in a neuropathic pain model

Nutr Neurosci. 2015 Jul;18(5):217-24. doi: 10.1179/1476830514Y.0000000119. Epub 2014 Mar 25.


Objectives: Previous studies have shown that essential oil containing (R)-(+)-limonene and α-phellandrene, extracted from fruits of Schinus terebinthifolius Raddi, exhibit anti-inflammatory activity. This work aimed to verify the antihyperalgesic and antidepressive actions of (R)-(+)-limonene, α-phellandrene, and essential oil from S. terebinthifolius fruits in spared nerve injury (SNI) model of neuropathic pain in rats.

Methods: In the present work, essential oil from fruits of S. terebinthifolius, as well as the pure (R)-(+)-limonene and α-phellandrene compounds, were assayed for their effects on SNI-induced mechanical and cold hyperalgesia, and depressive-like behavior (immobility in forced swim test) in rats. The locomotor activity was evaluated in open-field test.

Results: Oral administration for up to 15 days of essential oil of S. terebinthifolius (100 mg/kg), (R)-(+)-limonene (10 mg/kg), α-phellandrene (10 mg/kg), and also subcutaneous 10 mg/kg dose of ketamine (positive control) significantly inhibited SNI-induced mechanical hyperalgesia and increased immobility in the forced swim test. On the 15th day of oral treatment, α-phellandrene, but neither the essential oil from S. terebinthifolius nor (R)-(+)-limonene, prevented the SNI-induced increase in sensitivity to a cold stimulus. The oral treatment with essential oil (100 mg/kg) or with compounds (10 mg/kg) did not interfere on locomotor activity.

Discussion: Together, the results of the present work show that essential oil of S. terebinthifolius and compounds present in this oil, including (R)-(+)-limonene and α-phellandrene, exhibit antihyperalgesic effects against mechanical hyperalgesia, and are antidepressive, while only α-phellandrene inhibited cold hyperalgesia in SNI rats.

Keywords: Depression; Limonene; Neuropathic pain; Phellandrene; Rat; Schinus terebinthifolius fruits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anacardiaceae / chemistry*
  • Animals
  • Antidepressive Agents / pharmacology*
  • Cyclohexane Monoterpenes
  • Cyclohexenes / pharmacology*
  • Disease Models, Animal
  • Fruit / chemistry
  • Hyperalgesia / drug therapy
  • Limonene
  • Male
  • Monoterpenes / pharmacology*
  • Neuralgia / drug therapy*
  • Oils, Volatile / pharmacology*
  • Physical Conditioning, Animal
  • Plant Oils / pharmacology
  • Rats
  • Rats, Wistar
  • Terpenes / pharmacology*


  • Antidepressive Agents
  • Cyclohexane Monoterpenes
  • Cyclohexenes
  • Monoterpenes
  • Oils, Volatile
  • Plant Oils
  • Terpenes
  • alpha phellandrene
  • Limonene