Hydrogen enriched saline alleviates morphine tolerance via inhibiting neuroinflammation, GLT-1, GS nitration and NMDA receptor trafficking and functioning in the spinal cord of rats

2021 ◽  
Vol 755 ◽  
pp. 135847
Author(s):  
Qing Li ◽  
Haifang Zhang ◽  
Zhen Jia ◽  
Linlin Zhang ◽  
Yize Li ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Nmda Receptor ◽  
Morphine Tolerance ◽  
Receptor Trafficking

scholarly journals Inhibition of the phosphoinositide 3-kinase-AKT-cyclic GMP-c-Jun N-terminal kinase signaling pathway attenuates the development of morphine tolerance in a mouse model of neuropathic pain

2021 ◽  
Vol 17 ◽  
pp. 174480692110033
Author(s):  
Travis Okerman ◽  
Taylor Jurgenson ◽  
Madelyn Moore ◽  
Amanda H Klein
Keyword(s):  
Spinal Cord ◽  
Sciatic Nerve ◽  
Signaling Pathway ◽  
Intracellular Signaling ◽  
Morphine Tolerance ◽  
Spinal Nerve ◽  
Intracellular Signaling Pathway ◽  
Spinal Cord Dorsal ◽  
Phosphoinositide 3 Kinase ◽  
Induced Tolerance

Research presented here sought to determine if opioid induced tolerance is linked to activity changes within the PI3Kγ-AKT-cGMP-JNK intracellular signaling pathway in spinal cord or peripheral nervous systems. Morphine or saline injections were given subcutaneously twice a day for five days (15 mg/kg) to male C57Bl/6 mice. A separate cohort of mice received spinal nerve ligation (SNL) one week prior to the start of morphine tolerance. Afterwards, spinal cord, dorsal root ganglia, and sciatic nerves were isolated for quantifying total and phosphorylated- JNK levels, cGMP, and gene expression analysis of Pik3cg, Akt1, Pten, and nNos1. This pathway was downregulated in the spinal cord with increased expression in the sciatic nerve of morphine tolerant and morphine tolerant mice after SNL. We also observed a significant increase in phosphorylated- JNK levels in the sciatic nerve of morphine tolerant mice with SNL. Pharmacological inhibition of PI3K or JNK, using thalidomide, quercetin, or SP600125, attenuated the development of morphine tolerance in mice with SNL as measured by thermal paw withdrawal. Overall, the PI3K/AKT intracellular signaling pathway is a potential target for reducing the development of morphine tolerance in the peripheral nervous system. Continued research into this pathway will contribute to the development of new analgesic drug therapies.

Role of P2X7 Receptor-Mediated IL-18/IL-18R Signaling in Morphine Tolerance: Multiple Glial-Neuronal Dialogues in the Rat Spinal Cord

2012 ◽  
Vol 13 (10) ◽  
pp. 945-958 ◽  
Author(s):  
Meng-Ling Chen ◽  
Hong Cao ◽  
Yu-Xia Chu ◽  
Long-Zhen Cheng ◽  
Ling-Li Liang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
P2x7 Receptor ◽  
Morphine Tolerance ◽  
Rat Spinal Cord

Tu1875 BDNF Regulates NMDA Receptor Phosphorylation via the PLC/PKC Pathway in the Spinal Cord During Colitis

2015 ◽  
Vol 148 (4) ◽  
pp. S-925
Author(s):  
Miao Liu ◽  
Shanwei Shen ◽  
John R. Grider ◽  
Li-Ya Qiao
Keyword(s):  
Spinal Cord ◽  
Nmda Receptor ◽  
Receptor Phosphorylation

The N-methyl-D-aspartate (NMDA) receptor in skin, dorsal root ganglion and spinal cord: an ideal target gene for RNA interference therapy for pain relief

2017 ◽  
Vol 07 (03) ◽  
Author(s):  
Chia Chih Alex Tseng ◽  
Yuan Yi Chia ◽  
Chien Cheng Liu ◽  
Kuan Ming Feng ◽  
Ping Heng Tan
Keyword(s):  
Spinal Cord ◽  
Rna Interference ◽  
Nmda Receptor ◽  
Pain Relief ◽  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Target Gene

NMDA Receptor-Dependent Periodic Oscillations in Cultured Spinal Cord Networks

2001 ◽  
Vol 86 (6) ◽  
pp. 3030-3042 ◽  
Author(s):  
Edward W. Keefer ◽  
Alexandra Gramowski ◽  
Guenter W. Gross
Keyword(s):  
Spinal Cord ◽  
Nmda Receptor ◽  
Rhythmic Activity ◽  
Network Size ◽  
Observation Time ◽  
Network Activity ◽  
Early Postnatal Development ◽  
Bath Application ◽  
Coefficients Of Variation ◽  
Burst Patterns

Cultured spinal cord networks grown on microelectrode arrays display complex patterns of spontaneous burst and spike activity. During disinhibition with bicuculline and strychnine, synchronized burst patterns routinely emerge. However, the variability of both intra- and interculture burst periods and durations are typically large under these conditions. As a further step in simplification of synaptic interactions, we blocked excitatory AMPA synapses with 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzoquinoxaline-7-sulphonamide (NBQX), resulting in network activity mediated through the N-methyl-d-aspartate (NMDA) receptor (NMDAONLY). This activity was APV sensitive. The oscillation under NMDAONLY conditions at 37°C was characterized by a period of 2.9 ± 0.3 s (16 separate cultures). More than 98% of all neurons recorded participated in this highly rhythmic activity. The temporal coefficients of variation, reflecting the rhythmic nature of the oscillation, were 3.7, 4.7, and 4.9% for burst rate, burst duration, and interburst interval, respectively [mean coefficients of variation (CVs) for 16 cultures]. The oscillation persisted for at least 12 h without change (maximum observation time). Once established, it was not perturbed by agents that block mGlu receptors, GABABreceptors, cholinergic receptors, purinergic receptors, tachykinin receptors, serotonin (5-HT) receptors, dopamine receptors, electrical synapses, burst afterhyperpolarization, NMDA receptor desensitization, or the hyperpolarization-activated current. However, the oscillation was destroyed by bath application of NMDA (20–50 μM). These results suggest a presynaptic mechanism underlying this periodic rhythm that is solely dependent on the NMDA synapse. When the AMPA/kainate synapse was the sole driving force ( n = 6), the resulting burst patterns showed much higher variability and did not develop the highly periodic, synchronized nature of the NMDAONLYactivity. Network size or age did not appear to influence the reliability of expression of the NMDAONLYactivity pattern. For this reason, we suggest that the NMDAONLY condition unmasks a fundamental rhythmogenic mechanism of possible functional importance during periods of NMDA receptor-dominated activity, such as embryonic and early postnatal development.

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