Objective: To explore the inhibitory effect of spinal topical morphine on the dorsal horn projection neurons in nerve-injured rats and its mechanism.
Methods: Single-unit activity of dorsal horn projection neurons was recorded in anesthetized L(5)/L(6) nerve-ligated rats. Allodynia was determined by a behavior test in nerve-injured rats. The evoked neuronal responses to mechanical stimuli applied to the receptive field were determined before and after the spinal topical application of morphine, bicuculline plus morphine, strychnine plus morphine, and both bicuculline and strychnine plus morphine in normal, sham operation, and nerve-injured rats.
Results: Spinal topical application of 10 micromol/L morphine significantly inhibited the evoked responses of dorsal horn projection neurons in normal, sham, operation and nerve-injured rats. However, the inhibitory effect of morphine was significantly reduced in nerve-injured rats compared with that in normal and sham operation rats. Furthermore, the topical application of 20 micromol/L bicuculline had little effect on the inhibitory effect of morphine in nerve-injured rats but it almost abolished the effect of morphine in normal and sham operation rats. The glycine receptor antagonist strychnine at 4 micromol/L significantly decreased the effect of morphine in nerve-injured, normal, and sham operation rats.
Conclusion: The loss of tonic GABAergic inhibition contributes to the reduced inhibitory effect of morphine on dorsal horn projection neurons in nerve-injured rats.
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Neurobiol Pain
December 2024
School of Medical Sciences [Neuroscience], and the Brain & Mind Centre, The University of Sydney, NSW, 2006, Australia.
Chronic neuropathic pain is a debilitating condition that results from damage to the nervous system. Current treatments are largely ineffective, with limited understanding of the underlying mechanisms hindering development of effective treatments. Preclinical models of neuropathic pain have revealed that non-neural changes are important for the development of neuropathic pain, although these data are derived almost exclusively from post-mortem histological analyses.
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December 2024
Laboratory of Neurobiology, Department of Biology, Faculty of Chemistry and Biology, University of Santiago de Chile, Santiago, Chile.
Toxins (Basel)
September 2024
Department of Physical Medicine & Rehabilitation, Dongguk University College of Medicine, Goyang 10326, Republic of Korea.
This study aimed to assess the effects of the timing of administering botulinum neurotoxin A (BoNT/A) on nerve regeneration in rats. Sixty 6-week-old rats with a sciatic nerve injury were randomly divided into four groups: the immediately treated (IT) group (BoNT/A injection administered immediately post-injury), the delay-treated (DT) group (BoNT/A injection administered one week post-injury), the control group (saline administered one week post-injury), and the sham group (only skin and muscle incisions made). Nerve regeneration was assessed 3, 6, and 9 weeks post-injury using various techniques.
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August 2024
Neuroscience Drug Discovery Unit, Wolfson Sensory, Pain and Regeneration Centre, King's College London, Guy's Campus, London, United Kingdom.
Retinoic acid receptor β2 (RARβ2) is an emerging therapeutic target for spinal cord injuries (SCIs) with a unique multimodal regenerative effect. We have developed a first-in-class RARβ agonist drug, C286, that modulates neuron-glial pathways to induce functional recovery in a rodent model of sensory root avulsion. Here, using genome-wide and pathway enrichment analysis of avulsed rats' spinal cords, we show that C286 also influences the extracellular milieu (ECM).
View Article and Find Full Text PDFJ Pain
October 2024
Neuroscience Program/Brain Institute, Tulane University School of Medicine, New Orleans, Louisiana; SE LA Veterans Health Care System, Tulane University School of Medicine, New Orleans, Louisiana; Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana; Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana. Electronic address:
µ-Opioid receptor agonists, the gold standard for analgesia, come with significant side effects when used chronically. Tolerance, defined as the decrease in analgesic activity after repeated use, remains a vital therapeutic obstacle as it increases the likelihood of dose escalation and potentially lethal side effects like respiratory depression. Previous experiments have shown that the endomorphin-1 analog, ZH853, is a specific µ-opioid receptor agonist with reduced side effects like tolerance and glial activation following chronic central administration in pain-naive animals.
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