Regulation of cannabinoid and mu opioid receptors in rat lumbar spinal cord following neonatal capsaicin treatment

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.

Download Full-text

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

Download Full-text

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.

Download Full-text

Mu opioid receptors in developing human spinal cord

Journal of Anatomy ◽

10.1046/j.1469-7580.1999.19510011.x ◽

1999 ◽

Vol 195 (1) ◽

pp. 11-18 ◽

Cited By ~ 15

Author(s):

SUBRATA BASU RAY ◽

SHASHI WADHWA

Keyword(s):

Spinal Cord ◽

Opioid Receptors ◽

Mu Opioid Receptors ◽

Mu Opioid ◽

Human Spinal Cord

Download Full-text

Lipomeningocele associated with diplomyelia in a dog

Tierärztliche Praxis Ausgabe K Kleintiere / Heimtiere ◽

10.15654/tpk-170751 ◽

2018 ◽

Vol 46 (05) ◽

pp. 323-329 ◽

Cited By ~ 2

Author(s):

Nele Ondreka ◽

Sara Malberg ◽

Emma Laws ◽

Martin Schmidt ◽

Sabine Schulze

Keyword(s):

Spinal Cord ◽

Neurological Status ◽

Split Cord Malformation ◽

Lumbar Spinal Cord ◽

Histopathological Diagnosis ◽

Type I ◽

Thoracic Spinal Cord ◽

Thoracic Spinal ◽

Subcutaneous Mass ◽

Lumbar Spinal

SummaryA 2-year-old male neutered mixed breed dog with a body weight of 30 kg was presented for evaluation of a soft subcutaneous mass on the dorsal midline at the level of the caudal thoracic spine. A further clinical sign was intermittent pain on palpation of the area of the subcutaneous mass. The owner also described a prolonged phase of urination with repeated interruption and re-initiation of voiding. The findings of the neurological examination were consistent with a lesion localization between the 3rd thoracic and 3rd lumbar spinal cord segments. Magnetic resonance imaging revealed a spina bifida with a lipomeningocele and diplomyelia (split cord malformation type I) at the level of thoracic vertebra 11 and 12 and secondary syringomyelia above the aforementioned defects in the caudal thoracic spinal cord. Surgical resection of the lipomeningocele via a hemilaminectomy was performed. After initial deterioration of the neurological status postsurgery with paraplegia and absent deep pain sensation the dog improved within 2 weeks to non-ambulatory paraparesis with voluntary urination. Six weeks postoperatively the dog was ambulatory, according to the owner. Two years after surgery the owner recorded that the dog showed a normal gait, a normal urination and no pain. Histopathological diagnosis of the biopsied material revealed a lipomeningocele which confirmed the radiological diagnosis.

Download Full-text