Endocannabinoids Have Opposing Effects On Behavioral Responses To Nociceptive And Non-nociceptive Stimuli

The endocannabinoid system is thought to modulate nociceptive signaling making it a potential therapeutic target for treating pain. However, there is evidence that endocannabinoids have both pro- and anti-nociceptive effects. In previous studies using Hirudo verbana (the medicinal leech), endocannabinoids were found to depress nociceptive synapses, but enhance non-nociceptive synapses. Here we examined whether endocannabinoids have similar bidirectional effects on behavioral responses to nociceptive vs. non-nociceptive stimuli in vivo. Hirudo were injected with either the 2-arachidonoylglycerol (2-AG) or anandamide and tested for changes in response to nociceptive and non-nociceptive stimuli. Both endocannabinoids enhanced responses to non-nociceptive stimuli and reduced responses to nociceptive stimuli. These pro- and anti-nociceptive effects were blocked by co-injection of a TRPV channel inhibitor, which are thought to function as an endocannabinoid receptor. In experiments to determine the effects of endocannabinoids on animals that had undergone injury-induced sensitization, 2-AG and anandamide diminished sensitization to nociceptive stimuli although the effects of 2-AG were longer lasting. Sensitized responses to non-nociceptive stimuli were unaffected 2-AG or anandamide. These results provide evidence that endocannabinoids can have opposing effects on nociceptive vs. non-nociceptive pathways and suggest that cannabinoid-based therapies may be more appropriate for treating pain disorders in which hyperalgesia and not allodynia is the primary symptom.

• Publication year

  2017

• Venue

  Scientific Reports

• Publication date

  2017-07-19

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/s41598-017-06114-1PMID 28724917PMCID 5517658
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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