scholarly journals Contribution of adrenomedullin to the switch of G protein-coupled μ-opioid receptors from Gi to Gs in the spinal dorsal horn following chronic morphine exposure in rats

2016 ◽  
Vol 173 (7) ◽  
pp. 1196-1207 ◽  
Author(s):  
Dongmei Wang ◽  
Juan Zeng ◽  
Qi Li ◽  
Jianzhong Huang ◽  
Réjean Couture ◽  
...  
Keyword(s):  
G Protein ◽  
Dorsal Horn ◽  
Opioid Receptors ◽  
Spinal Dorsal Horn ◽  
Chronic Morphine ◽  
Spinal Dorsal ◽  
G Protein Coupled ◽  
Μ Opioid Receptors

Endogenous Opioid Peptides Acting at μ-Opioid Receptors in the Dorsal Horn Contribute to Midbrain Modulation of Spinal Nociceptive Neurons

1998 ◽  
Vol 79 (2) ◽  
pp. 677-687 ◽  
Author(s):  
Dénes Budai ◽  
Howard L. Fields
Keyword(s):  
Dorsal Horn ◽  
Opioid Receptors ◽  
Spinal Dorsal Horn ◽  
Endogenous Opioid Peptides ◽  
Endogenous Opioid ◽  
Nociceptive Neurons ◽  
Dorsal Horn Neurons ◽  
Spinal Dorsal ◽  
Spinal Dorsal Horn Neurons ◽  
Μ Opioid Receptors

Budai, Dénes and Howard L. Fields. Endogenous opioid peptides acting at μ-opioid receptors in the dorsal horn contribute to midbrain modulation of spinal nociceptive neurons. J. Neurophysiol. 79: 677–687, 1998. Activation of neurons in the midbrain periaqueductal gray (PAG) inhibits spinal dorsal horn neurons and produces behavioral antinociception in animals and analgesia in humans. Although dorsal horn regions modulated by PAG activation contain all three opioid receptor classes (μ, δ, and κ), as well as enkephalinergic interneurons and terminal fields, descending opioid-mediated inhibition of dorsal horn neurons has not been demonstrated. We examined the contribution of dorsal hornμ-opioid receptors to the PAG-elicited descending modulation of nociceptive transmission. Single-unit extracellular recordings were made from rat sacral dorsal horn neurons activated by noxious heating of the tail. Microinjections of bicuculline (BIC) in the ventrolateral PAG led to a 60–80% decrease in the neuronal responses to heat. At the same time, the responses of the same neurons to iontophoretically applied NMDA or kainic acid were not consistently inhibited. The inhibition of heat-evoked responses by PAG BIC was reversed by iontophoretic application of the selective μ-opioid receptor antagonists, d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) and d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP). A similar effect was produced by naloxone; however, naloxone had an excitatory influence on dorsal horn neurons in the absence of PAG-evoked descending inhibition. This is the first demonstration that endogenous opioids acting via spinal μ-opioid receptors contribute to brain stem control of nociceptive spinal dorsal horn neurons. The inhibition appears to result in part from presynaptic inhibition of afferents to dorsal horn neurons.

CONTRIBUTION OF MU AND DELTA OPIOID RECEPTORS TO MORPHINE ANALGESIA IN THE SPINAL DORSAL HORN OF CATS

1989 ◽  
Vol 71 (Supplement) ◽  
pp. A629
Author(s):  
K. Omote ◽  
L. M. Kitahata ◽  
J. G. Collins ◽  
K. Nakatani
Keyword(s):  
Dorsal Horn ◽  
Opioid Receptors ◽  
Spinal Dorsal Horn ◽  
Morphine Analgesia ◽  
Spinal Dorsal ◽  
Delta Opioid Receptors

scholarly journals 100 Hz Electroacupuncture Alleviated Chronic Itch and GRPR Expression Through Activation of Kappa Opioid Receptors in Spinal Dorsal Horn

2021 ◽  
Vol 15 ◽  
Author(s):  
Hong-Ping Li ◽  
Xiao-Yu Wang ◽  
Chao Chen ◽  
Jing-Jing Li ◽  
Chi Yu ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
Diethyl Ether ◽  
Opioid Receptors ◽  
Spinal Dorsal Horn ◽  
Underlying Mechanism ◽  
Kappa Opioid Receptors ◽  
Effective Frequency ◽  
Kappa Opioid ◽  
Spinal Dorsal ◽  
Chronic Itch

BackgroundClinical studies have shown that electroacupuncture (EA) alleviates chronic itch. Gastrin-releasing peptide receptor (GRPR) and dynorphin (DYN) in the spinal dorsal horn positively or negatively regulate itch, respectively. However, which frequency of EA is effective on relieving chronic itch and reducing the expression of GRPR, whether DYN-A in the spinal cord is involved in the underlying mechanism of the antipruritus effect of EA remains unknown.MethodsThe mixture of acetone and diethyl ether (1:1) [designated as AEW (acetone/diethyl ether and water) treatment] was used to induce the dry skin model of chronic itch. EA was applied to Quchi (LI11) and Hegu (LI4). Western blot was used to detect the expression of GRPR and DYN-A. Immunofluorescence was used to detect the expression of DYN-A.ResultsThe AEW administration induced remarkable spontaneous scratching, enhanced the expression of GRPR, and reduced the expression of DYN-A. Compared with the sham EA, 2 Hz EA, or 15 Hz EA group, 100 Hz EA was the most effective frequency for relieving chronic itch, reducing the expression of GRPR, and increasing the expression of DYN-A in the cervical dorsal horn. Furthermore, intraperitoneal injection of kappa opioid receptors (KORs) antagonist nor-Binaltorphimine dihydrochloride (nor-BNI) significantly reversed the effect of 100 Hz EA on the inhibition of both itching behavior and GRPR expression.ConclusionEA at 100 Hz is the most effective frequency that inhibits chronic itch and GRPR expression through activation of KORs in the spinal dorsal horn, which can effectively guide the clinical treatment and improve the antipruritic effect of acupuncture.

Melatonin Reduce Morphine-Induced Hyperalgesia and Tolerance of Rats via melatonin-MT1-PKCγ Pathway.

2020 ◽  
Author(s):  
Yuchao Fan ◽  
Xiao Liang ◽  
Bixin Zheng ◽  
Li Song
Keyword(s):  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Morphine Tolerance ◽  
Melatonin Level ◽  
Chronic Morphine ◽  
Lower Serum ◽  
Regulation Of Expression ◽  
Spinal Dorsal ◽  
Sd Rats ◽  
Morphine Administration

Abstract Background: Morphine is commonly used for treating acute and chronic pain. However, its using is complicated with tolerance and hyperalgesia. Endogenous melatoninergic system is involved in development of tolerance and hyperalgesia induced by chronic morphine administration, but the precise mechanism remains unknown. Methods: 18 male SD rats were randomly divided into Saline(Sal), Morphine(Mor) and Morphine+Chelerythrine (Mor+Che) group (n = 6, respectively). Each group were received twice-daily intrathecal injections of saline (10μl), morphine (15μg/10μl) or morphine (15μg/5μl)+ chelerythrine (5μg/5μl) for consecutive 9 days, respectively. MWT and TWL of all animals were recorded on day 1, 3, 5, 7, 9. The morphine tolerance was depicted as MPAE on day 1, 3, 5, 7, 9 and on day 10 which can be used to calculate for ED50 of each group. Then we determined the serum level of melatonin by ELISA and expression of MOR , MT1, MT2 and PKCγ by RT-qPCR and WB in spinal dorsal horn of three group rats.Results: Comparing with Sal group, the Mor group exhibited a significant lower serum melatonin level and up-regulation of expression of the MT1, MT2 and PKCγ in the spinal dorsal horn. Co-administration of chelerythrine with morphine not only attenuates morphine-induced hyperalgesia and tolerance, but also increases the down-regulation of serum melatonin level) and reduces the up-regulation of expression of MT1 and PKCγ in spinal dorsal horn compared with Mor group. Conclusion：Melatonin can reduce morphine-induced hyperalgesia and tolerance of rats via melatonin-MT1-PKCγ pathway.

Functional μ Opioid Receptors Are Reduced in the Spinal Cord Dorsal Horn of Diabetic Rats

2002 ◽  
Vol 97 (6) ◽  
pp. 1602-1608 ◽  
Author(s):  
Shao-Rui Chen ◽  
Kristi L. Sweigart ◽  
Joan M. Lakoski ◽  
Hui-Lin Pan
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Opioid Receptors ◽  
Spinal Dorsal Horn ◽  
Diabetic Rats ◽  
Spinal Cord Dorsal Horn ◽  
Mu Opioid Receptors ◽  
Mu Opioid ◽  
Spinal Dorsal ◽  
Spinal Cord Dorsal

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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