Long-term depression of nociceptive synapses by non-nociceptive afferent activity: Role of endocannabinoids, Ca2+, and calcineurin

Sharleen Yuan, Brian D. Burrell

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Activity in non-nociceptive afferents is known to produce long-lasting decreases in nociceptive signaling, often referred to as gate control, but the cellular mechanisms mediating this form of neuroplasticity are poorly understood. In the leech, activation of non-nociceptive touch (T) mechanosensory neurons induces a heterosynaptic depression of nociceptive (N) synapses that is endocannabinoid-dependent. This heterosynaptic, endocannabinoid-dependent long-term depression (ecLTD) is observed where the T- and N-cells converge on a common postsynaptic target, in this case the motor neuron that innervates the longitudinal muscles (L-cells) that contributes to a defensive withdrawal reflex. Depression in the nociceptive synapse required both presynaptic and postsynaptic increases in intracellular Ca2+. Activation of the Ca2+-sensitive protein phosphatase calcineurin was also required, but only in the presynaptic neuron. Heterosynaptic ecLTD was unaffected by antagonists for NMDA or metabotropic glutamate receptors, but was blocked by the 5-HT2 receptor antagonist ritanserin. Depression was also blocked by the CB1 receptor antagonist rimonabant, but this is thought to represent an effect on a TRPV-like receptor. This heterosynaptic, endocannabinoid-dependent modulation of nociceptive synapses represents a novel mechanism for regulating how injury-inducing or painful stimuli are transmitted to the rest of the central nervous system.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalBrain Research
StatePublished - Jun 15 2012
Externally publishedYes


  • Endocannabinoids
  • Gate control
  • Heterosynaptic
  • LTD
  • Leech
  • Nociception

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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