Noxious mechanical stimulation evokes the segmental release of opioid peptides that induce mu-opioid receptor internalization in the presence of peptidase inhibitors.

Brain Research
Lijun LaoJuan Carlos G Marvizón

Abstract

The internalization of mu-opioid receptors (MORs) provides an ideal way to locate areas of opioid peptide release. We used this method to study opioid release in the spinal cord evoked by noxious stimuli in anesthetized rats. Previous studies have shown that opioids released in the spinal cord produce MOR internalization only when they are protected from peptidase degradation. Accordingly, rats were implanted with chronic intrathecal catheters that were used to inject a mixture of peptidase inhibitors (amastatin, captopril and phosphoramidon) onto the lumbar spinal cord. Five minutes later, a noxious stimulus was delivered to the paw. Lumbar spinal segments were double-stained with antibodies against MORs and neurokinin 1 receptors (NK1Rs) using immunofluorescence. Mechanical stimulation of the hindpaw consisted of repeated 10 s clamps with a hemostat for 10 min. In the ipsilateral dorsal horn, the stimulus produced abundant NK1R internalization in segments L3-L6, and a more modest but significant MOR internalization in segments L5 and L6. In the contralateral dorsal horn, NK1R was substantially lower and MOR internalization was negligible. The same mechanical stimulus applied to a forepaw did not produce NK1R or MOR internaliz...Continue Reading

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Citations

Feb 28, 2013·Neuromodulation : Journal of the International Neuromodulation Society·Louis P Vera-PortocarreroLisa M Johanek
Mar 25, 2015·Cell Reports·Shanna L BowmanManojkumar A Puthenveedu
Dec 11, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Karol WtorekAnna Janecka
Jun 3, 2021·Journal of Clinical Medicine·Thomas PerreaultBarry C Gendron
Oct 2, 2009·Peptides·Richard J Bodnar

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