Faculty Opinions recommendation of Blocking mu opioid receptors in the spinal cord prevents the analgesic action by subsequent systemic opioids.

Background The mechanisms of decreased spinal analgesic potency of morphine in neuropathic pain are not fully known. Agonist-stimulated [35S]GTPgammaS receptor autoradiography has been used to measure receptor activation of G proteins in vitro. Using this technique, we determined changes in the functional mu opioid receptors in the spinal dorsal horn in diabetic rats. Methods Rats were rendered diabetic with an intraperitoneal injection of streptozotocin. The lumbar spinal cord was obtained from age-matched normal and diabetic rats 4 weeks after streptozotocin treatment. [D-Ala2,N-MePhe4,Gly5-ol]-enkephalin (DAMGO, 10 microm)-stimulated [35S]GTPgammaS binding was performed in both tissue sections and isolated membranes. Results The DAMGO-stimulated [35S]GTPgammaS binding in the spinal dorsal horn was significantly reduced (approximately 37%) in diabetic rats compared with normal rats. However, [35S]GTPgammaS bindings in the spinal dorsal horn stimulated by other G protein-coupled receptor agonists, including [D-Pen2,D-Pen5]-enkephalin, R(-)N6-(2-phenylisopropyl)-adenosine, and WIN-55212, were not significantly altered in diabetic rats. The basal [35S]GTPgammaS binding in the spinal dorsal horn was slightly (approximately 13%) but significantly increased in diabetic rats. Western blot analysis revealed no significant difference in the expression of the alpha subunits of G(i) and G(o) proteins in the dorsal spinal cord between normal and diabetic rats. Conclusions These data suggest that the functional mu opioid receptors in the spinal cord dorsal horn of diabetic rats are reduced. The impaired functional mu opioid receptors in the spinal cord may constitute one of the mechanisms underlying the reduced spinal analgesic effect of mu opioids in diabetic neuropathic pain.

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High resolution radioautographic localization of [125I]FK-33-824-labelled mu opioid receptors in the spinal cord of normal and deafferented rats

Neuroscience ◽

10.1016/0306-4522(91)90427-p ◽

1991 ◽

Vol 43 (1) ◽

pp. 197-209 ◽

Cited By ~ 68

Author(s):

C. Gouardères ◽

A. Beaudet ◽

J.-M. Zajac ◽

J. Cros ◽

R. Quirion

Keyword(s):

Spinal Cord ◽

High Resolution ◽

Opioid Receptors ◽

Mu Opioid Receptors ◽

Mu Opioid

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Regular physical activity reduces the percentage of spinally projecting neurons that express mu-opioid receptors from the RVM

10.1101/2020.04.27.064923 ◽

2020 ◽

Author(s):

KA Sluka ◽

SJ Kolker ◽

J Danielson ◽

L Rasmussen

Keyword(s):

Physical Activity ◽

Spinal Cord ◽

Opioid Receptors ◽

Tryptophan Hydroxylase ◽

Regular Physical Activity ◽

Mu Opioid Receptors ◽

Physically Active ◽

Nociceptive Neurons ◽

Mu Opioid ◽

Running Wheels

AbstractRegular physical activity/exercise is an effective non-pharmacological treatment for individuals with chronic pain. Central inhibitory mechanisms, involving serotonin and opioids, are critical to analgesia produced by regular physical activity. The RVM sends projections to the spinal cord to inhibit or facilitate nociceptive neurons and plays a key role in exercise-induced analgesia. The goal of these studies was to examine if regular physical activity modifies RVM-spinal cord circuitry. Male and female mice received Fluoro-Gold placed on the spinal cord to identify spinally projecting neurons from the rostral ventromedial medulla (RVM) and the nucleus raphe obscuris/nucleus raphe pallidus (NRO/NRP), dermorphin-488 into caudal medulla to identify mu-opioid receptors, and were immunohistochemically stained for either phosphorylated-N-methyl-D-aspartate subunit NR1 (p-NR1) to identify excitatory neurons or tryptophan hydroxylase (TPH) to identify serotonin neurons. The percentage of dermorphin-488-positive cells that stained for p-NR1 (or TPH), and the percentage of dermorphin-488-positive cells that stained for p-NR1 (or TPH) and Fluoro-Gold was calculated.Physically active animals were provided running wheels in their cages for 8 weeks and compared to sedentary animals without running wheels. Animals with chronic muscle pain, induced by two intramuscular injections of pH 4.0, were compared to sham controls (pH 7.2). Physically active animals had less mu-opioid expressing neurons projecting to the spinal cord when compared to sedentary animals in the RVM, but not the NRO/NRP. No changes were observed for TPH. These data suggest that regular exercise alters central facilitation so that there is less descending facilitation to result in a net increase in inhibition.Summary StatementPhysically active animals has less mu-opioid expressing neurons projecting to the spinal cord in the RVM, but not the NRO/NRP, when compared to sedentary animals.

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