The Antinociceptive Effect of Intrathecal Administration of Glycine Transporter-2 Inhibitor ALX1393 in a Rat Acute Pain Model

2010 ◽  
Vol 110 (2) ◽  
pp. 615-621 ◽  
Author(s):  
Yasunori Haranishi ◽  
Koji Hara ◽  
Tadanori Terada ◽  
Seiya Nakamura ◽  
Takeyoshi Sata
Keyword(s):  
Acute Pain ◽  
Antinociceptive Effect ◽  
Intrathecal Administration ◽  
Pain Model ◽  
Glycine Transporter ◽  
Glycine Transporter 2

scholarly journals Spinal Cord Glycine Transporter 2 Mediates Bilateral ST35 Acupoints Sensitization in Rats with Knee Osteoarthritis

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Fuhai Bai ◽  
Yongyuan Ma ◽  
Haiyun Guo ◽  
Yuheng Li ◽  
Feifei Xu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Mast Cell ◽  
Knee Osteoarthritis ◽  
Dorsal Horn ◽  
Intrathecal Administration ◽  
Mast Cell Degranulation ◽  
Spinal Cord Dorsal Horn ◽  
Glycine Transporter ◽  
Mechanical Threshold ◽  
Glycine Transporter 2

The concept of “acupoint sensitization” refers to the functional status of acupoint switches from silent to active under pathological conditions. In clinic, acupoint sensitization provides important guidance for acupoints selection in different diseases. However, the mechanism behind this phenomenon remains unclear. We generated a model of knee osteoarthritis (KOA) by intra-articular injection of monosodium iodoacetate (MIA) into the left knee of rats. The paw withdrawal mechanical threshold (PWMT) and the total number of mast cells as well as mast cell degranulation rate (MCDR) of acupoint tissue were used to test whether the acupoints were sensitized. The results showed that KOA resulted in a reduced mechanical threshold and elevated total number of mast cell as well as mast cell degranulation rate at bilateral ST35 (Dubi) but not GB37 (Guangming) or nonacupoint area. The acupoint sensitization was accompanied by upregulation of glycine transporter 2 (GlyT2) and reduction of extracellular glycine levels in the bilateral dorsal horns of the spinal cord at L3-5. Selective inhibition of GlyT2 or intrathecal administration of glycine attenuated ST35 acupoint sensitization. The sensitization of bilateral ST35 was blocked after intraspinal GlyT2 short hairpin (sh) RNA (GlyT2-shRNA) microinjection to specifically downregulate GlyT2 expression in the left side (ipsilateral) L3-5 spinal cord dorsal horn before MIA injection. Moreover, electroacupuncture (EA) stimulation at ST35 ameliorated articular pathological lesions and improved KOA-related pain behaviors. GlyT2-shRNA injection reversed EA-induced pain relief but not EA-induced reduction of joint lesions. Overall, this study demonstrated that spinal GlyT2, especially elevated GlyT2 expression in the ipsilateral dorsal horn of the spinal cord, is a crucial mediator of ST35 acupoint sensitization in KOA rats.

scholarly journals Intrathecal administration of neuronostatin induces an antinociceptive effect in a mouse visceral pain model

2020 ◽  
Vol 6 (4) ◽  
pp. 344-354
Author(s):  
Tingji Shao ◽  
Shaobin Yang ◽  
Peng Yu
Keyword(s):  
Visceral Pain ◽  
Antinociceptive Effect ◽  
Intrathecal Administration ◽  
Writhing Test ◽  
New Approach ◽  
Pain Model ◽  
Antinociceptive Effects ◽  
Μ Opioid Receptor ◽  
G Protein Coupled ◽  
Dose Dependent

Neuronostatin (NST) is a peptide encoded by the somatostatin gene that serves important physiological functions in diverse tissues. Previous studies have shown that intracerebroventricular administration of NST induces antinociceptive effects and hyperalgesic effects as determined by the tail immersion assay and formalin test, respectively. In the present study, we aimed to evaluate the effects of intrathecal (i.t.) injection of NST on nociception in a model of visceral pain, and determine possible mechanisms of action in mice. NST (1, 3, 6, or 12 nmol) was administered to mice, leading to a dose‐dependent antinociceptive effect as determined by the acetic acid‐induced writhing test in mice. NST (1 nmol) also enhanced the antinociceptive effect of morphine (2.5 and 5 μg/kg) in the spine. Naloxone and β‐funaltrexamine hydrochloride significantly antagonized the antinociceptive effect of NST. The expression of G‐protein‐coupled receptor 107 (GPR107) protein and the phosphorylation of PKA at Thr197 were increased after i.t. administration of NST, suggesting that the μ‐opioid receptor and GPR107/PKA signaling pathway are involved in the analgesic response. In conclusion, i.t. injection of NST may potentially be used as a new approach in the mediation of visceral pain.

Synergistic antinociceptive effect of a calcium channel blocker and a TRPV1 blocker in an acute pain model in mice

Life Sciences ◽  
2017 ◽  
Vol 182 ◽  
pp. 122-128 ◽  
Author(s):  
Manuella R. Palhares ◽  
Juliana F. Silva ◽  
Marcio Junior S. Rezende ◽  
Duana C. Santos ◽  
Cláudio A. Silva-Junior ◽  
...  
Keyword(s):  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Acute Pain ◽  
Channel Blocker ◽  
Antinociceptive Effect ◽  
Pain Model

scholarly journals The activation of galanin receptor 2 plays an antinociceptive effect in nucleus accumbens of rats with neuropathic pain

2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Yan Dong ◽  
Chong-Yang Li ◽  
Xiao-Min Zhang ◽  
Ya-Nan Liu ◽  
Shuang Yang ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Nucleus Accumbens ◽  
Pain Threshold ◽  
Antinociceptive Effect ◽  
Galanin Receptor ◽  
Pain Model ◽  
Withdrawal Threshold ◽  
Neuropathic Pain Model ◽  
Galanin Receptors ◽  
Intact Rats

AbstractOur previous research has shown that galanin plays an antinociceptive effect via binding to galanin receptors (GalRs) in nucleus accumbens (NAc). This study focused on the involvement of GalR2 in galanin-induced antinociceptive effect in NAc of neuropathic pain rats. The chronic constriction injury of sciatic nerve (CCI) was used to mimic neuropathic pain model. The hind paw withdrawal latency (HWL) to thermal stimulation and hind paw withdrawal threshold (HWT) to mechanical stimulation were measured as the indicators of pain threshold. The results showed that 14 and 28 days after CCI, the expression of GalR2 was up-regulated in bilateral NAc of rats, and intra-NAc injection of GalR2 antagonist M871 reversed galanin-induced increases in HWL and HWT of CCI rats. Furthermore, intra-NAc injection of GalR2 agonist M1145 induced increases in HWL and HWT at day 14 and day 28 after CCI, which could also be reversed by M871. Finally, we found that M1145-induced antinociceptive effect in NAc of CCI rats was stronger than that in intact rats. These results imply that the GalR2 is activated in the NAc from day 14 to day 28 after CCI and GalR2 is involved in the galanin-induced antinociceptive effect in NAc of CCI rats.

The neuronal glycine transporter 2 interacts with the PDZ domain protein syntenin-1

2004 ◽  
Vol 26 (4) ◽  
pp. 518-529 ◽  
Author(s):  
Koji Ohno ◽  
Michael Koroll ◽  
Oussama El Far ◽  
Petra Scholze ◽  
Jesus Gomeza ◽  
...  
Keyword(s):  
Pdz Domain ◽  
Glycine Transporter ◽  
Domain Protein ◽  
Glycine Transporter 2

scholarly journals A comparative study of antinociceptive effect of paroxetine with pethidine in acute pain in albino rats

2017 ◽  
Vol 6 (7) ◽  
pp. 1728
Author(s):  
Manju Gari ◽  
Kumari Ranjeeta ◽  
Lakhan Majhee ◽  
Akhilesh Kumar ◽  
Sumit Kumar Mahato
Keyword(s):  
Acute Pain ◽  
Water Immersion ◽  
Antinociceptive Effect ◽  
Warm Water ◽  
Albino Rats ◽  
Thermal Method ◽  
Average Weight ◽  
Tail Flick ◽  
Immersion Method ◽  
Standard Drug

Background: Pain is the most common reason patients seek medical care. Increased level of monoamines (serotonin and norepinephrine) in synaptic clefts lead to changes in pain threshold and induce antinociception. The study was carried out to evaluate antinociceptive effect of paroxetine in albino rats and to probe into its possible mechanism of action. The study was carried out to evaluate anti-nociceptive effect of paroxetine in albino rats.Methods: Male Albino rats of average weight 150-240gms were used. The drugs used were paroxetine 5mg/Kg, pethidine 5mg/kg (standard drug). Anti-nociceptive effect tested by using thermal method i.e. Tail flick response and Tail warm water immersion method.Results: In this study, Anti-nociceptive effect of respective drugs were measured by using two methods i.e. tail flick test and tail warm water immersion method at 0 min., 30 min., 60 min. and 90min.after administration of drugs. Reaction time started to increase from baseline at 0 min. and peak effect was seen at 60 min. then it started to decrease at 90 min. in almost all the groups except in control group.Conclusions: Paroxetine have significant analgesic effect in acute pain, which may be mediated via central and peripheral mechanisms. Efficacy of Paroxetine is almost equal to that of standard drug pethidine in acute pain management.

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