Abstract
Chronic Opioid Potentiates Presynaptic but Impairs Postsynaptic N-Methyl-d-aspartic Acid Receptor Activity in Spinal Cords: IMPLICATIONS FOR OPIOID HYPERALGESIA AND TOLERANCE
Highlights
We determined the role of presynaptic N-methyl-D-aspartate receptor (NMDAR) activity in spinal cords in opioid-induced hyperalgesia and tolerance
To determine the role of NMDARs in the control of glutamatergic input to dorsal horn neurons, we tested the effect of AP5, a selective NMDAR antagonist [26], on Spontaneous EPSCs (sEPSCs)
The morphine-induced reduction in the amplitude of NMDAR currents of lamina II neurons in vehicle-treated rats (n ϭ 11 neurons) was abolished in RTX-treated rats (n ϭ 16 neurons, Fig. 7, C and D). These results suggest that increased glutamate release from TRPV1-expressing primary afferents by chronic morphine is responsible for the diminished postsynaptic NMDAR activity of dorsal horn neurons
Summary
We determined the role of presynaptic N-methyl-D-aspartate receptor (NMDAR) activity in spinal cords in opioid-induced hyperalgesia and tolerance. We recently showed that in spinal lamina I and II neurons, brief opioid exposure can cause a long-lasting increase in glutamate release from nociceptive primary afferents (i.e. opioid-induced primary afferent hyperactivity) through activation of presynaptic NMDARs [14] It is not clear, how pre- and postsynaptic NMDARs help regulate glutamatergic synaptic input to spinal dorsal horn neurons after chronic opioid treatment. Chronic morphine administration leads to a large reduction in postsynaptic NMDAR activity, which results from increased glutamate release from transient receptor potential vanilloid type 1 (TRPV1)-expressing primary afferents This new information is important for understanding the mechanisms involved in NMDAR plasticity at the spinal level and their roles in opioid-induced hyperalgesia and analgesic tolerance
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