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.

scholarly journals Chemical Composition and Antinociceptive Potential of Plinia edulis Fruits Peels

2018 ◽  
Vol 13 (5) ◽  
pp. 1934578X1801300
Author(s):  
Luciane Angela Nottar Nesello ◽  
Adriana Campos ◽  
Karla Capistrano ◽  
Fátima de Campos Buzzi ◽  
Valdir Cechinel Filho
Keyword(s):  
Chemical Composition ◽  
Antinociceptive Effect ◽  
Reference Drug ◽  
Writhing Test ◽  
Maslinic Acid ◽  
Pain Model ◽  
Antinociceptive Effects ◽  
Dose Dependent ◽  
Dose Dependent Effect ◽  
Different Doses

The present study deals with the chemical composition and antinociceptive effects of Plinia edulis fruit peels, analyzed by writhing, formalin, glutamate and capsaicin tests and comparison with two reference analgesic drugs, acetylsalicylic acid and acetaminophen. Phytochemical analyses of the nonpolar fraction (dichloromethane) obtained from the peels of P. edulis fruits revealed the presence of two triterpenes, maslinic acid and ursolic acid. The methanol extract of P. edulis peels showed a pronounced antinociceptive activity in the writhing test, with inhibition of 91.3% at 10 mg/kg, and its dichloromethane and ethyl acetate fractions presented inhibition of 68.3% and 51.5%, respectively. Maslinic acid showed a dose-dependent effect with inhibition of 60.8% at a dose of 10 mg/kg and ID50 value of 3.31 (2.75 to 4.0) mg/kg. The dichloromethane fraction, evaluated in the formalin-induced pain model at a dose of 10 mg/kg, showed a significant effect on both phases of pain. Maslinic acid was evaluated at different doses (1, 3 and 6 mg/kg) and presented a dose-dependent profile in both phases of pain, being more effective than the reference drug (acetaminophen), which was evaluated at 10 mg/kg. The dichloromethane fraction also inhibited the pain induced by glutamate and capsaicin by around 54% and 44%, respectively, whereas maslinic acid was more effective against glutamate, with 62.5% inhibition at 6 mg/kg, and 32% inhibition against capsaicin-induced pain. The results demonstrated that the pronounced antinociceptive effect presented by P. edulis fruits peels is related, at least in part, to the presence of the triterpenes evidenced in this study.

scholarly journals Morphine Antinociception Restored by Use of Methadone in the Morphine-Resistant Inflammatory Pain State

2020 ◽  
Vol 11 ◽  
Author(s):  
Chizuko Watanabe ◽  
Asami Komiyama ◽  
Masaru Yoshizumi ◽  
Shinobu Sakurada ◽  
Hirokazu Mizoguchi
Keyword(s):  
Opioid Receptors ◽  
Inflammatory Pain ◽  
Antinociceptive Effect ◽  
Thermal Hyperalgesia ◽  
Expression Level ◽  
Pain Model ◽  
Mk 801 ◽  
Antinociceptive Effects ◽  
Pain State ◽  
Intraperitoneal Treatment

The antinociceptive effect of methadone in the morphine-resistant inflammatory pain state was described in the paw-withdrawal test using the complete Freund’s adjuvant (CFA)-induced mouse inflammatory pain model. After intraplantar (i.pl.) injection of CFA, thermal hyperalgesia was observed in the ipsilateral paw. The antinociceptive effects of subcutaneous (s.c.) injection of morphine, fentanyl, and oxycodone against thermal hyperalgesia in the inflammatory pain state were reduced in the ipsilateral paw 7 days after CFA pretreatment. On the contrary, the antinociceptive effect of s.c. injection of methadone was maintained in the ipsilateral paw 7 days after CFA pretreatment. The suppressed morphine antinociception in the CFA model mice was bilaterally restored following s.c. treatment with methadone 20 min prior to or 3 days after CFA pretreatment. The suppressed morphine antinociception was also bilaterally restored by intraperitoneal treatment with MK-801 30 min prior to CFA pretreatment; however, the s.c. injection of morphine 30 min prior to CFA pretreatment failed to restore the suppressed morphine antinociception in the CFA model mice. The expression level of mRNA for µ-opioid receptors 7 days after i.pl. pretreatment was not significantly changed by i.pl. pretreatment with CFA or s.c. pretreatment with methadone. In conclusion, methadone is extremely effective against thermal hyperalgesia in the morphine-resistant inflammatory pain state, and restores suppressed morphine antinociception in the inflammatory pain state without altering the expression level of mRNA for µ-opioid receptors.

scholarly journals Antinociceptive Effect of Rat D-Serine Racemase Inhibitors, L-Serine-O-Sulfate, and L-Erythro-3-Hydroxyaspartate in an Arthritic Pain Model

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Claudio Laurido ◽  
Alejandro Hernández ◽  
Teresa Pelissier ◽  
Luis Constandil
Keyword(s):  
Chronic Pain ◽  
Aspartic Acid ◽  
Antinociceptive Effect ◽  
Serine Racemase ◽  
Pain Model ◽  
Acid Receptor ◽  
Culture Cells ◽  
Antinociceptive Effects ◽  
Nmdar Activation

N-methyl-D-aspartic acid receptor (NMDAr) activation requires the presence of D-serine, synthesized from L-serine by a pyridoxal 5′-phosphate-dependent serine racemase (SR). D-serine levels can be lowered by inhibiting the racemization of L-serine. L-serine-O-sulfate (LSOS) and L-erythro-3-hydroxyaspartate (LEHA), among others, have proven to be effective in reducing the D-serine levels in culture cells. It is tempting then to try these compounds in their effectiveness to decrease nociceptive levels in rat arthritic pain. We measured the C-reflex paradigm and wind-up potentiation in the presence of intrathecally injected LSOS (100 μg/10 μL) and LEHA (100 μg/10 μL) in normal and monoarthritic rats. Both compounds decreased the wind-up activity in normal and monoarthritic rats. Accordingly, all the antinociceptive effects were abolished when 300 μg/10 μL of D-serine were injected intrathecally. Since noin vivoresults have been presented so far, this constitutes the first evidence that SR inhibitions lower the D-serine levels, thus decreasing the NMDAr activity and the consequent development and maintenance of chronic pain.

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

Antinociceptive Profiles of Platycodin D in the Mouse

2004 ◽  
Vol 32 (02) ◽  
pp. 257-268 ◽  
Author(s):  
Seong-Soo Choi ◽  
Eun-Jung Han ◽  
Tae-Hee Lee ◽  
Ki-Jung Han ◽  
Han-Kyu Lee ◽  
...  
Keyword(s):  
Antinociceptive Effect ◽  
Control Level ◽  
Tail Flick ◽  
Triterpene Saponins ◽  
Tail Flick Test ◽  
Platycodin D ◽  
Pain Models ◽  
Antinociceptive Effects ◽  
Dose Dependent ◽  
Higher Doses

Platycodin D (PD), one of several triterpene saponins, was isolated from roots of Platycodon grandiflorum. We previously reported that intracerebroventricular (i.c.v.) administration of PD showed an antinociceptive effect as measured by the tail-flick assay. However, its exact role in the regulation of antinociception in the various types of pain models has not yet been characterized. Thus, we attempted to find antinociceptive profiles of PD in various pain models. PD administered intraperitoneally (i.p.), i.c.v. or intrathecally (i.t.) showed antinociceptive effects in dose-dependent manners as measured by the tail-flick, writhing and formalin tests. In the tail-flick test, PD at the low doses reached the peak after 15 minutes and returned to the control level after 60 minutes. However, higher doses of PD showed a strong antinociception at least for 1 hour. PD administered i.t. showed stronger antinociception than that induced by i.c.v. administration PD in both tail-flick and writhing tests. In the formalin test, PD administered i.p., i.c.v. or i.t. showed antinociceptive effects during both the first (direct nociceptive stimulation) and second (late inflammatory) phases. Pretreatment with naltrexone i.p., i.c.v. or i.t. did not affect PD-induced inhibition of the tail-flick response. Our results suggest that PD shows a strong antinociceptive effect on the tail-flick, writhing and formalin tests, acting on central nervous system. However, PD-induced antinociception may not be mediated by the opioid receptors.

Nociceptin /Orphanin FQ Peptide (NOP) Receptor Modulators: An Update in Structure-Activity Relationships

2018 ◽  
Vol 25 (20) ◽  
pp. 2353-2384 ◽  
Author(s):  
Carlo Mustazza ◽  
Stefano Pieretti ◽  
Francesca Marzoli
Keyword(s):  
Partial Agonist ◽  
Orphanin Fq ◽  
Structure Activity Relationships ◽  
Airway Constriction ◽  
Structure Activity ◽  
Antinociceptive Effects ◽  
Μ Opioid Receptor ◽  
Receptor Modulators ◽  
G Protein Coupled ◽  
Higher Doses

Nociceptin /Orphanin FQ Peptide” receptor (NOPr) is a G-protein-coupled receptor with the nociceptin/orphanin FQ peptide (N/OFQ) as endogenous agonist. It is expressed in the nervous system as well as in some non-neural tissues. Its activation has pronociceptive effect at the supraspinal level, whereas at the spinal level it produces nociceptive effects at low doses and antinociceptive effects at higher doses. NOPr is also involved in mood and blood pressure regulation, immunoregulation, airway constriction, feeding, urination, bowel motility, learning and memory. Selective NOPr agonists have been tested clinically as anxiolytics and antitussives, and the antagonists as analgesics, antidepressants and in the treatment of alcohol addiction. Two NOPr radioligands have also been tested in humans as neuroimaging agents. Furthermore, the partial agonist peptide SER100 and N/OFQ have been used in clinical trials, respectively for congestive heart failure and overactive bladder. The evidence of interactions between NOP and μ-opioid receptor (MOPr) receptors has been exploited in the use of mixed NOPr/MOPr modulators as analgesics and in the treatment of drug addiction. These drugs are devoid of typical opioid liabilities. In this review, we outline the latest advances in the structure-activity relationships (SAR) of NOPr agonists and antagonists, with emphasis on affinity, activity, selectivity and pharmacokinetic features.

The Antinociceptive Effects of Anticonvulsants in a Mouse Visceral Pain Model

2008 ◽  
Vol 106 (6) ◽  
pp. 1897-1903 ◽  
Author(s):  
Radica M. Stepanović-Petrović ◽  
Maja A. Tomić ◽  
Sonja M. Vučković ◽  
Sonja Paranos ◽  
Nenad D. Ugrešić ◽  
...  
Keyword(s):  
Visceral Pain ◽  
Pain Model ◽  
Antinociceptive Effects

scholarly journals Antinociceptive and Abuse Potential Effects of Cannabinoid/Opioid Combinations in a Chronic Pain Model in Rats

2019 ◽  
Vol 9 (11) ◽  
pp. 328 ◽  
Author(s):  
Alsalem ◽  
Altarifi ◽  
Haddad ◽  
Aldossary ◽  
Kalbouneh ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Antinociceptive Effect ◽  
Abuse Liability ◽  
Synthetic Cannabinoid ◽  
Male Rats ◽  
Management Approach ◽  
Additional Risk ◽  
Antinociceptive Effects ◽  
Self Stimulation ◽  
Dose Dependent

Chronic pain is a persistent and debilitating health problem. Although the use of analgesics such as opioids is useful in mitigating pain, their prolonged use is associated with unwanted effects including abuse liability. This study assesses the antinociceptive effect of combining subtherapeutic doses of two opioids (morphine or tramadol) with the synthetic cannabinoid CP55940 (2-[(1R,2R,5R)-5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-5-(2-methyloctan -2-yl)phenol). It also evaluates the associated adverse effects of these drugs and combinations. Adult male rats were injected with intraplantar complete Freund’s adjuvant (CFA) to produce mechanical allodyia. Antinociceptive effect of morphine, tramadol, the synthetic cannabinoid CP55940, or their combinations was evaluated three to nine days post-CFA injections. Intracranial self-stimulation (ICSS) was utilized to evaluate the abuse liability of these drugs or their combinations. All drugs alone produced a dose-dependent antinociceptive effect. Morphine produced minimal effect on ICSS, but both tramadol and CP55940 produced dose-dependent depression of ICSS. Morphine at a dose of 0.32 mg/kg enhanced the antinociceptive effects of CP55940, in that, CP55940 produced antinociception at a lower dose (0.1 mg/kg) when compared to the vehicle. The aforementioned combinations did not change CP55940-induced depression of ICSS. On the other hand, tramadol failed to enhance the antinociceptive effect of CP55940. Our data suggest that combining CP55940 with morphine, but not tramadol, shows a better antinociceptive profile with no additional risk of abuse liability, which represents a potential pain management approach.

Evaluation of the Analgesic Effect of Aqueous Extract of Brugmansia suaveolens Flower in Mice: Possible Mechanism Involved

2010 ◽  
Vol 11 (4) ◽  
pp. 345-350 ◽  
Author(s):  
Ana Luiza Muccillo-Baisch ◽  
Alexander Garcia Parker ◽  
Gianni Peraza Cardoso ◽  
Marta Regina Cezar-Vaz ◽  
Maria Cristina Flores Soares
Keyword(s):  
Aqueous Extract ◽  
Benzodiazepine Receptors ◽  
Antinociceptive Effect ◽  
Dependent Manner ◽  
Hot Plate Test ◽  
Antinociceptive Effects ◽  
Brugmansia Suaveolens ◽  
The Central Nervous System ◽  
Dose Dependent ◽  
Abdominal Constriction

The study was conducted to test the aqueous extract of Brugmansia suaveolens (AEBs) flowers for their antinociceptive effects in mice. In the hot plate test, a significant increase in reaction time for two doses of AEBs at 60, 90, 120, and 150 min after treatment was noted. Pretreatment of animals with naloxone (5 mg/kg, intraperitoneally [IP]) left the antinociceptive effect of AEBs at a dose of 100 mg/kg unaffected at 60, 90, 120, and 150 min after treatment and at a dose of 300 mg/kg at 30 min but not at 90, 120, and 150 min. In the writhing test, the AEBs significantly inhibited acetic acid—induced abdominal constriction and was equally potent at both doses. Pretreatment with naloxone (5 mg/kg, IP) left the antinociceptive effect of both doses of AEBs unaffected. Pretreatment with NG-nitro-L-arginine methyl ester (L-NAME; 20 mg/kg, IP) caused a significant change in the number of abdominal constrictions but did not change the antinociceptive effect of AEBs. Pretreatment of animals with methylene blue also did not change the effect of AEBs on the number of writhing movements in mice. Flumazenil (5 mg/kg, IP) antagonized the antinociceptive effects of diazepam and also reversed the antinociceptive effect of AEBs. AEBs showed a depressant effect on the central nervous system, and the treatment of mice with pentobarbital combined with AEBs increased the animals’ sleeping time in a dose-dependent manner. These results suggest that the antinociceptive activity of AEBs may be related in part to benzodiazepine receptors, although peripheral mechanisms cannot be excluded.

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