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Different spinal effects of opioid agonists on spinal and spino-bulbo-spinal reflexes in rats
1Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Abstract:
The effects of morphine-HCl (MOR), methionine-enkephalin (ME) and dynorphin (DYN) on spinal and spino-bulbo-spinal (SBS) reflexes were studied. Although spinal intrathecal administration of MOR (15 micrograms) did not produce any apparent effect on these reflexes, systemically administered MOR (3 mg/kg i.v.) reduced the electrical toe stimulation-induced SBS reflex. Furthermore, MOR (3 mg/kg i.v.) increased the polysynaptic reflex induced by electrical stimulation of low-threshold dorsal root afferents in intact (non-spinal) rats, but not in spinal rats. Intrathecally administered DYN (0.5 and 5 micrograms) reduced both the electrical toe stimulation-induced spinal and SBS reflexes, while ME (15 micrograms) only reduced the SBS reflex. These results indicate the physiological multiplicity of spinal opioid receptors. MOR may affect supraspinal nuclei but not the spinal pathway which possesses MOR-sensitive opioid receptors, whereas ME and DYN affect spinal opioid peptide receptors and modulate the reflex activities in which they participate.
Insights
Morphine (MOR), methionine-enkephalin (ME), and dynorphin (DYN) differentially affect spinal reflexes. Dynorphin and methionine-enkephalin modulate spinal opioid receptors, while morphine acts supraspinally.
Area of Science:
- Neuroscience
- Pharmacology
- Physiology
Background:
- Opioid receptors play a crucial role in pain modulation.
- Understanding the distinct roles of different opioid peptides in spinal reflexes is essential for developing targeted analgesics.
Purpose of the Study:
- To investigate the differential effects of morphine-HCl (MOR), methionine-enkephalin (ME), and dynorphin (DYN) on spinal and spino-bulbo-spinal (SBS) reflexes.
- To elucidate the physiological multiplicity and localization of spinal opioid receptors.
Main Methods:
- Administration of MOR, ME, and DYN via intrathecal and intravenous routes in rats.
- Assessment of spinal and SBS reflexes induced by electrical toe stimulation and dorsal root afferent stimulation.
- Comparison of effects in intact and spinal rats.
Main Results:
- Systemic MOR reduced SBS reflexes and increased polysynaptic reflexes in intact rats, but not spinal rats.
- Intrathecal DYN reduced both spinal and SBS reflexes.
- Intrathecal ME reduced only SBS reflexes.
- Spinal intrathecal MOR had no apparent effect on these reflexes.
Conclusions:
- Opioid peptides exhibit distinct actions on spinal reflex pathways.
- MOR primarily affects supraspinal pathways, while ME and DYN act on spinal opioid receptors.
- These findings highlight the physiological diversity of spinal opioid receptor systems.