Salvinorin A reduces neuropathic nociception in the insular cortex of the rat

Eur J Pain. 2018 Feb;22(2):311-318. doi: 10.1002/ejp.1120. Epub 2017 Oct 4.


Background: Neuropathic pain is one of the most important challenges in public health. The search for novel treatments is important for an adequate relief without adverse effects. In this sense salvinorin A (SA), the main diterpene of the medicinal plant Salvia divinorum is an important antinociceptive compound, which acts as a potent agonist of kappa opioid receptor (KOR) and cannabinoid CB1 receptors.

Methods: We evaluated nociceptive responses in a neuropathic pain model induced by the sciatic nerve ligature (SNL) in the right hind paw, after the microinjection of SA, Salvinorin B (SB), KOR and CB1 antagonists directly in the insular cortex (IC) in male wistar rats.

Results: We found a potent antinociceptive effect with the administration of SA. Moreover, this effect was blocked by the administration of a KOR antagonist as well as the administration of a CB1 antagonist.

Conclusion: Salvinorin A has a potent antinociceptive effect when is administered centrally in the IC by the interaction with KOR and CB1 receptors.

Significance: We show evidence on the effectiveness of the administration of salvinorin A in the IC in a rodent model of neuropathic pain. These results support the use of novel compounds like SA as a therapeutic alternative for neuropathic pain relief.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebral Cortex / drug effects*
  • Diterpenes, Clerodane / pharmacology*
  • Diterpenes, Clerodane / therapeutic use
  • Male
  • Narcotic Antagonists / pharmacology
  • Neuralgia / drug therapy*
  • Nociception / drug effects*
  • Rats
  • Rats, Wistar
  • Receptor, Cannabinoid, CB1 / agonists
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors
  • Receptors, Opioid, kappa / agonists


  • Diterpenes, Clerodane
  • Narcotic Antagonists
  • Receptor, Cannabinoid, CB1
  • Receptors, Opioid, kappa
  • salvinorin A