scholarly journals Loss of SUR1 subtype KATP channels alters antinociception and locomotor activity after opioid administration

2020 ◽  
Author(s):  
Gerald Sakamaki ◽  
Kayla Johnson ◽  
Megan Mensinger ◽  
Eindray Hmu ◽  
Amanda H. Klein
Keyword(s):  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Katp Channels ◽  
Acute Administration ◽  
Superficial Dorsal Horn ◽  
Wild Type ◽  
Opioid Administration ◽  
Potassium Flux ◽  
Μ Opioid Receptor

AbstractBackgroundOpioid signaling can occur through several downstream mediators and influence analgesia as well as reward mechanisms in the nervous system. KATP channels are downstream targets of the μ opioid receptor and contribute to morphine-induced antinociception.AimsThe aim of the present work was to assess the role of SUR1-subtype KATP channels in antinocicpetion and hyperlocomotion of synthetic and semi-synthetic opioids.MethodsAdult male and female mice wild-type (WT) and SUR1 deficient (KO) mice were assessed for mechanical and thermal antinociception after administration of either buprenorphine, fentanyl, or DAMGO. Potassium flux was assessed in the dorsal root ganglia and superficial dorsal horn cells in WT and KO mice. Hyperlocomotion was also assessed in WT and KO animals after buprenorphine, fentanyl, or DAMGO administration.ResultsSUR1 KO mice had attenuated mechanical antinociception after systemic administration of buprenorphine, fentanyl, and DAMGO. Potassium flux was also attenuated in the dorsal root ganglia and spinal cord cells after acute administration of buprenorphine and fentanyl. Hyperlocomotion after administration of morphine and buprenorphine was potentiated in SUR1 KO mice, but was not seen after administration of fentanyl or DAMGO.ConclusionsThese results suggest SUR1-subtype KATP channels mediate the antinociceptive response of several classes of opioids (alkaloid and synthetic/semi-synthetic), but may not contribute to the “drug-seeking” behaviors of all classes of opioids.

scholarly journals Role of β-arrestin-2 in short- and long-term opioid tolerance in the dorsal root ganglia

2020 ◽  
Author(s):  
Karan H. Muchhala ◽  
Joanna C. Jacob ◽  
William L. Dewey ◽  
Hamid I. Akbarali
Keyword(s):  
G Protein ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Opioid Tolerance ◽  
Male Mice ◽  
Wild Type ◽  
Drg Neurons ◽  
Antinociceptive Tolerance

Abstractβ-arrestin-2 has been implicated in the mechanism of opioid-induced antinociceptive tolerance. G-protein-biased agonists with reduced β-arrestin-2 activation are being investigated as safer alternatives to clinically-used opioids. Opioid-induced analgesic tolerance is classically considered as centrally-mediated, but recent reports implicate nociceptive dorsal root ganglia (DRG) neurons as critical mediators in this process. Here, we investigated the role of β-arrestin-2 in the mechanism of opioid tolerance in DRG nociceptive neurons using β-arrestin-2 knockout mice and the G-protein-biased μ-opioid receptor agonist, TRV130. Whole-cell current-clamp electrophysiology experiments revealed that 15-18-hour overnight exposure to 10 μM morphine in vitro induced acute tolerance in β-arrestin-2 wild-type but not knockout DRG neurons. Furthermore, in wild-type DRG neurons circumventing β-arrestin-2 activation by overnight treatment with 200 nM TRV130 attenuated tolerance. Similarly, in β-arrestin-2 knockout male mice acute antinociceptive tolerance induced by 100 mg/kg morphine s.c. was prevented in the warm-water tail-withdrawal assay. Treatment with 30 mg/kg TRV130 s.c. also inhibited antinociceptive tolerance in wild-type mice. Alternately, in β-arrestin-2 knockout DRG neurons tolerance induced by 7-day in vivo exposure to 50 mg morphine pellet was conserved. Likewise, β-arrestin-2 deletion did not mitigate in vivo antinociceptive tolerance induced by 7-day exposure to 25 mg or 50 mg morphine pellet in both female or male mice, respectively. Consequently, these results indicated that β-arrestin-2 mediates acute but not chronic opioid tolerance in DRG neurons and to antinociception. This suggests that opioid-induced antinociceptive tolerance may develop even in the absence of β-arrestin-2 activation, and thus significantly affect the clinical utility of biased agonists.

On the role of glial gaba uptake: Studies with dorsal root ganglia

1980 ◽  
Vol 5 ◽  
pp. 77-81 ◽  
Author(s):  
P.M. Headley ◽  
M. Desarmenien ◽  
G. Linck ◽  
F. Santangelo ◽  
P. Feltz
Keyword(s):  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Gaba Uptake ◽  
Uptake Studies

Uncx4.1 is required for the formation of the pedicles and proximal ribs and acts upstream of Pax9

Development ◽  
2000 ◽  
Vol 127 (11) ◽  
pp. 2251-2258 ◽  
Author(s):  
A. Mansouri ◽  
A.K. Voss ◽  
T. Thomas ◽  
Y. Yokota ◽  
P. Gruss
Keyword(s):  
Cell Adhesion ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Homeobox Gene ◽  
Axial Skeleton ◽  
Adhesion Properties ◽  
Marker Analysis ◽  
Targeted Mutation ◽  
Differential Cell

The expression of the homeobox gene Uncx4.1 in the somite is restricted to the caudal half of the newly formed somite and sclerotome. Here we show that mice with a targeted mutation of the Uncx4.1 gene exhibit defects in the axial skeleton and ribs. In the absence of Uncx4.1, pedicles of the neural arches and proximal ribs are not formed. In addition, dorsal root ganglia are disorganized. Histological and marker analysis revealed that Uncx4.1 is not necessary for somite segmentation. It is required to maintain the condensation of the caudal half-sclerotome, from which the missing skeletal elements are derived. The loss of proximal ribs in Pax1/Pax9 double mutants and the data presented here argue for a role of Uncx4.1 upstream of Pax9 in the caudolateral sclerotome. Our results further indicate that Uncx4.1 may be involved in the differential cell adhesion properties of the somite.

Role of GM-CSF in a mouse model of experimental autoimmune prostatitis

2019 ◽  
Vol 317 (1) ◽  
pp. F23-F29 ◽  
Author(s):  
Yaxiao Liu ◽  
Yan Li ◽  
Qinggang Liu ◽  
Zonglong Wu ◽  
Jianfeng Cui ◽  
...  
Keyword(s):  
Mouse Model ◽  
Dorsal Root Ganglia ◽  
Knockout Mice ◽  
Dorsal Root ◽  
Prostate Tissue ◽  
Mrna Levels ◽  
Gm Csf ◽  
Mouse Prostate ◽  
Experimental Autoimmune

The etiology of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is still unknown. Granulocyte macrophage colony-stimulating factor (GM-CSF) has been shown to play an important role in the development of autoimmune and inflammatory diseases. Here, we investigated the expression and function of GM-CSF in patients with CP/CPPS and in a mouse model of experimental autoimmune prostatitis (EAP). GM-CSF mRNA levels were detected in expressed prostatic secretions samples from patients with CP/CPPS and in prostate tissue from a mouse model of EAP. The expression of GM-CSF receptor in mouse prostate and dorsal root ganglia were determined using PCR and immunohistochemistry. Behavioral testing and inflammation scoring were performed to evaluate the role of GM-CSF in disease development and symptom severity of EAP using GM-CSF knockout mice. mRNA levels of putative nociceptive and inflammatory markers were measured in the prostate after the induction of EAP. Elevated GM-CSF mRNA levels were observed in expressed prostatic secretions samples from patients with CP/CPPS compared with healthy volunteers. GM-CSF mRNA was also significantly increased in prostate tissue of the EAP mice model. The expression of GM-CSF receptors was confirmed in mouse prostate and dorsal root ganglia. GM-CSF knockout mice showed fewer Infiltrating leukocytes and pain symptoms after the induction of EAP. Deletion of GM-CSF significantly diminished EAP-induced increases of chemokine (C-C motif) ligand 2, chemokine (C-C motif) ligand 3, and nerve growth factor mRNA expression. The results indicated that GM-CSF plays a functional role in the pathogenesis of EAP. GM-CSF may function as a signaling mediator for both inflammation and pain transduction in CP/CPPS.

scholarly journals Sensation of Abdominal Pain Induced by Peritoneal Carcinomatosis Is Accompanied by Changes in the Expression of Substance P and μ-Opioid Receptors in the Spinal Cord of Mice

2012 ◽  
Vol 117 (4) ◽  
pp. 847-856 ◽  
Author(s):  
Masami Suzuki ◽  
Minoru Narita ◽  
Minami Hasegawa ◽  
Sadayoshi Furuta ◽  
Tomoyuki Kawamata ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Abdominal Pain ◽  
Substance P ◽  
Peritoneal Carcinomatosis ◽  
Opioid Receptor ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Receptor Expression ◽  
Tumor Bearing ◽  
Μ Opioid Receptor

Background Patients with peritoneal carcinomatosis often report abdominal pain, which is relatively refractory to morphine. It has been considered that a new animal model is required to investigate the mechanism of abdominal pain for the development of optimal treatments for this type of pain. Methods To prepare a peritoneal carcinomatosis model, highly peritoneal-seeding gastric cancer cells, 60As6, were implanted into the abdominal cavity. The nociceptive modality for pain-related behavior was assessed in terms of withdrawal behavior in response to mechanical stimuli and hunching behavior. Tissue samples from mouse dorsal root ganglia and spinal cord were subject to immunohistochemistry and real-time reverse transcription polymerase chain reaction. Results Mice with peritoneal dissemination showed significant hypersensitivity of the abdomen to mechanical stimulation and spontaneous visceral pain-related behavior. There was a significant increase in c-Fos-positive cells in the spinal cord in tumor-bearing mice. Those mice exhibited a remarkable increase in substance P-positive neurons in the dorsal root ganglia (control vs. tumor, 15.4 ± 1.1 vs. 24.2 ± 3.6, P < 0.05, n = 3). A significant decreases in μ-opioid receptor expression mainly in substance P-positive neurons was observed in tumor-bearing mice (69.3 ± 4.9 vs. 38.7 ± 0.9, P < 0.05, n = 3), and a relatively higher dose of morphine was required to significantly reverse the abdominal hypersensitivity. Conclusion Both the up-regulation of substance P and down-regulation of μ-opioid receptor seen in the dorsal root ganglia may be, at least in part, responsible for the abdominal pain-like state associated with peritoneal carcinomatosis.

Role of myosin Va in neuritogenesis of chick dorsal root ganglia nociceptive neurons

2013 ◽  
Vol 38 (3) ◽  
pp. 388-394 ◽  
Author(s):  
Tatiane Y. N. Kanno ◽  
Enilza M. Espreafico ◽  
Chao Yun Irene Yan
Keyword(s):  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Nociceptive Neurons ◽  
Myosin Va
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