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- W1563349291 endingPage "9594" @default.
- W1563349291 startingPage "9580" @default.
- W1563349291 abstract "Due to its distinct pharmacological profile and lower incidence of adverse events compared with other opioids, buprenorphine is considered a safe option for pain and substitution therapy. However, despite its wide clinical use, little is known about the synaptic effects of buprenorphine in nociceptive pathways. Here, we demonstrate dose-dependent, bimodal effects of buprenorphine on transmission at C-fiber synapses in rat spinal cord dorsal horn in vivo. At an analgesically active dose of 1500 μg·kg(-1), buprenorphine reduced the strength of spinal C-fiber synapses. This depression required activation of spinal opioid receptors, putatively μ1-opioid receptors, as indicated by its sensitivity to spinal naloxone and to the selective μ1-opioid receptor antagonist naloxonazine. In contrast, a 15,000-fold lower dose of buprenorphine (0.1 μg·kg(-1)), which caused thermal and mechanical hyperalgesia in behaving animals, induced an enhancement of transmission at spinal C-fiber synapses. The ultra-low-dose buprenorphine-induced synaptic facilitation was mediated by supraspinal naloxonazine-insensitive, but CTOP-sensitive μ-opioid receptors, descending serotonergic pathways, and activation of spinal glial cells. Selective inhibition of spinal 5-hydroxytryptamine-2 receptors (5-HT2Rs), putatively located on spinal astrocytes, abolished both the induction of synaptic facilitation and the hyperalgesia elicited by ultra-low-dose buprenorphine. Our study revealed that buprenorphine mediates its modulatory effects on transmission at spinal C-fiber synapses by dose dependently acting on distinct μ-opioid receptor subtypes located at different levels of the neuraxis." @default.
- W1563349291 created "2016-06-24" @default.
- W1563349291 creator A5015747930 @default.
- W1563349291 creator A5031005362 @default.
- W1563349291 creator A5041159525 @default.
- W1563349291 creator A5045087840 @default.
- W1563349291 creator A5080591591 @default.
- W1563349291 date "2015-07-01" @default.
- W1563349291 modified "2023-09-25" @default.
- W1563349291 title "Pronociceptive and Antinociceptive Effects of Buprenorphine in the Spinal Cord Dorsal Horn Cover a Dose Range of Four Orders of Magnitude" @default.
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- W1563349291 doi "https://doi.org/10.1523/jneurosci.0731-14.2015" @default.
- W1563349291 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4571500" @default.