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Brain Res. 2012 Jun 15;1460:1-11. doi: 10.1016/j.brainres.2012.04.030. Epub 2012 Apr 24.

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

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1
Sanford School of Medicine at The University of South Dakota, Division of Basic Biomedical Sciences, Neuroscience Group, 414 E. Clark Street, Lee Med Bldg, Vermillion, SD, USA.

Abstract

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.

PMID:
22578358
DOI:
10.1016/j.brainres.2012.04.030
[Indexed for MEDLINE]
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