5-HT1A Receptors Mediate Analgesia Induced by Emulsified Sevoflurane in Thermal Nociception but Have Little Effect on Chemical Nociception

Pharmacology ◽  
2017 ◽  
Vol 100 (1-2) ◽  
pp. 25-30
Author(s):  
Chen Yan ◽  
Dai Ti-jun ◽  
Li Xin ◽  
Cao Gao ◽  
Jiang Shen ◽  
...  
Keyword(s):  
Analgesic Effect ◽  
Intraperitoneal Injection ◽  
Serotonin Receptor ◽  
Intrathecal Injection ◽  
Tail Flick ◽  
Hot Plate Test ◽  
Thermal Nociception ◽  
Tail Flick Latency ◽  
Specific Antagonist ◽  
The Relationship

Objective: The study aimed to investigate the relationship between the analgesic effect of sevoflurane and 5-serotonin receptor 1A (5-HT1A R) in the spinal cords of mice. Methods: Analgesic mouse models were established by intraperitoneal injection of emulsified sevoflurane, and the influence of p-MPPF (a specific antagonist of 5-HT1A Rs) intrathecal injection on the changes in tail-flick latency in tail-withdrawal test, pain threshold in hot-plate test (HPPT), and writhing times in acetic acid-induced writhing test were recorded. Results: Intraperitoneal injection of emulsified sevoflurane alone produced an analgesic effect (p < 0.05). p-MPPF (2, 4, and 8 μg) alone had no impact on tail-flick latency, HPPT, and writhing times in mice (p > 0.05). The 3 doses of p-MPPF reduced the tail-flick latency or HPPT. p-MPPF 8 μg can increase the writhing times (p < 0.05) in analgesic mice with sevoflurane, while p-MPPF 2 and 4 μg did not affect the writhing times. Conclusion: 5-HT1A Rs in the spinal cord may be an important target for the analgesic effect of sevoflurane on the thermal nociception, but it has little relation to the anti-chemical chemical nociceptive effect of sevoflurane.

scholarly journals New ibuprofen derivatives with thiazolidine-4-one scaffold with improved pharmaco-toxicological profile

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ioana-Mirela Vasincu ◽  
Maria Apotrosoaei ◽  
Sandra Constantin ◽  
Maria Butnaru ◽  
Liliana Vereștiuc ◽  
...  
Keyword(s):  
Analgesic Effect ◽  
Visceral Pain ◽  
Biological Effects ◽  
Maximum Effect ◽  
Tail Flick ◽  
Paw Edema ◽  
Cell Viability Assay ◽  
Thermal Nociception ◽  
Analgesic Effects ◽  
Anti Inflammatory

Abstract Background Aryl-propionic acid derivatives with ibuprofen as representative drug are very important for therapy, being recommended especially for anti-inflammatory and analgesic effects. On other hand 1,3-thiazolidine-4-one scaffold is an important heterocycle, which is associated with different biological effects such as anti-inflammatory and analgesic, antioxidant, antiviral, antiproliferative, antimicrobial etc. The present study aimed to evaluated the toxicity degree and the anti-inflammatory and analgesic effects of new 1,3-thiazolidine-4-one derivatives of ibuprofen. Methods For evaluation the toxicity degree, cell viability assay using MTT method and acute toxicity assay on rats were applied. The carrageenan-induced paw-edema in rat was used for evaluation of the anti-inflammatory effect while for analgesic effect the tail-flick test, as thermal nociception in rats and the writhing assay, as visceral pain in mice, were used. Results The toxicological screening, in terms of cytotoxicity and toxicity degree on mice, revealed that the ibuprofen derivatives (4a-n) are non-cytotoxic at 2 μg/ml. In addition, ibuprofen derivatives reduced carrageenan-induced paw edema in rats, for most of them the maximum effect was recorded at 4 h after administration which means they have medium action latency, similar to that of ibuprofen. Moreover, for compound 4d the effect was higher than that of ibuprofen, even after 24 h of administration. The analgesic effect evaluation highlighted that 4 h showed increased pain inhibition in reference to ibuprofen in thermal (tail-flick assay) and visceral (writhing assay) nociception models. Conclusions The study revealed for ibuprofen derivatives, noted as 4 m, 4 k, 4e, 4d, a good anti-inflammatory and analgesic effect and also a safer profile compared with ibuprofen. These findings could suggest the promising potential use of them in the treatment of inflammatory pain conditions.

Dexmedetomidine Injection into the Locus Ceruleus Produces Antinociception

1996 ◽  
Vol 84 (4) ◽  
pp. 873-881. ◽  
Author(s):  
Tian-Zhi Guo ◽  
Jian-Yu Jiang ◽  
Ann E. Buttermann ◽  
Mervyn Maze
Keyword(s):  
Spinal Cord ◽  
Pertussis Toxin ◽  
Antinociceptive Effect ◽  
Intrathecal Injection ◽  
Locus Ceruleus ◽  
Tail Flick ◽  
Sprague Dawley ◽  
Tail Flick Latency ◽  
Pharmacologically Active ◽  
Sites Of Action

Background Alpha(2)-Adrenergic agonists such as clonidine and dexmedetomidine are known to produce sedation and analgesia in humans. The sedative effect of these agents is thought to occur through supraspinal pathways, involving the locus ceruleus (LC) and its projections in rats. While the antinociceptive response to alpha(2) agonists, given intrathecally, is mediated predominantly in the spinal cord, other sites of action have not been systematically studied. The authors examined whether alpha(2)-adrenergic receptors in the LC mediate an antinociceptive effect. Methods For administration of different drugs into the LC, guide cannulas were placed with their tips in the LC in male Sprague-Dawley rats. Dexmedetomidine (3.5 micrograms/0.2 microliter) was microinjected into the LC through the cannula, or given systemically by intraperitoneal injecton (50 micrograms/kg). The antinociceptive effect of dexmedetomidine was measured using the tail-flick latency response. To determine the sites through which dexmedetomidine injection into the LC produces antinociception, the authors examined whether this response could be perturbed by the specific alpha(2)-adrenergic antagonists atipamezole and L659,066 and pertussis toxin administered either into the LC or intrathecally before injection of dexmedetomidine systemically or directly into the LC. To eliminate the possibility that drug administered in one site (LC or intrathecal) could reach the other site, the dispositional characteristics of radiolabeled dexmedetomidine (LC) or atipamezole (intrathecal) were studied. Results Dexmedetomidine placed into the LC produces a dose-dependent increase in the tail-flick latency. This antinociceptive effect was blocked by pertussis toxin and by the alpha(2) antagonists atipamezole and L659,066 placed in the LC. Intrathecal administration of atipamezole and pertussis toxin also blocked the antinociceptive effect of dexmedetomidine placed in the LC. (3)H-dexmedetomidine introduced into the LC did not reach the spinal cord in pharmacologically active concentrations; also, intrathecally administered (3)H-atipamezole did not reach the LC in appreciable amounts. The systemic administration of dexmedetomidine produced an increase in tail-flick latency, and this effect was attenuated by the injection of atipamezole and L659,066 into the LC. Conclusions Part of the mechanism by which dexmedetomidine produces an antinociceptive effect is by an action directly on the LC, demonstrated by these studies in which antinociception produced by injection of this drug into the LC can be blocked by specific alpha(2) antagonists injected into the LC. Furthermore, the action of dexmedetomidine in the LC in turn may result in an increase in activation of alpha(2) adrenoceptors in the spinal cord, because the antinociceptive effect of LC dexmedetomidine injection also can be blocked by intrathecal injection of antipamezole and pertussis toxin.

Periaqueductal Gray Metabotropic Glutamate Receptor Subtype 7 and 8 Mediate Opposite Effects on Amino Acid Release, Rostral Ventromedial Medulla Cell Activities, and Thermal Nociception

2007 ◽  
Vol 98 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Ida Marabese ◽  
Francesca Rossi ◽  
Enza Palazzo ◽  
Vito de Novellis ◽  
Katarzyna Starowicz ◽  
...  
Keyword(s):  
Metabotropic Glutamate Receptor ◽  
Gaba Release ◽  
Periaqueductal Gray ◽  
Rostral Ventromedial Medulla ◽  
Tail Flick ◽  
Receptor Subtype ◽  
Thermal Nociception ◽  
Metabotropic Glutamate ◽  
Tail Flick Latency ◽  
Ventromedial Medulla

The current study has investigated the involvement of periaqueductal gray (PAG) metabotropic glutamate subtype 7 and 8 receptors (mGluR7 and mGluR8) in modulating rostral ventromedial medulla (RVM) ongoing and tail flick–related on and off cell activities. Our study has also investigated the role of PAG mGluR7 on thermoceptive threshold and PAG glutamate and GABA release. Intra-ventrolateral PAG ( S)-3,4-dicarboxyphenylglycine [( S)-3,4-DCPG (2 and 4 nmol/rat)] or N,N I-dibenzhydrylethane-1,2-diamin dihydrochloride (AMN082, (1 and 2 nmol/rat), selective mGluR8 and mGluR7 agonists, respectively, caused opposite effects on the ongoing RVM on and off cell activities. Tail flick latency was increased or decreased by ( S)-3,4-DCPG or AMN082 (2 nmol/rat), respectively. ( S)-3,4-DCPG reduced the pause and delayed the onset of the off cell pause. Conversely, AMN082 increased the pause and shortened the onset of off cell pause. ( S)-3,4-DCPG or AMN082 did not change the tail flick-induced onset of on-cell peak firing. The tail flick latency and its related electrophysiological effects induced by ( S)-3,4-DCPG or AMN082 were prevented by (RS)-α-methylserine-o-phosphate (100 nmol/rat), a group III mGluR antagonist. Intra-ventrolateral PAG perfusion with AMN082 (10 and 25 μM), decreased thermoceptive thresholds and glutamate extracellular levels. A decrease in GABA release was also observed. These results show that stimulation of PAG mGluR8 or mGluR7 could either relieve or worsen pain perception. The opposite effects on pain behavior correlate with the opposite roles played by mGluR7 and mGluR8 on glutamate and GABA release and the ongoing and tail flick-related activities of the RVM on and off cells.

scholarly journals Composition and Antinociceptive Activity of the Essential Oil from Protium Heptaphyllum Resin

2007 ◽  
Vol 2 (12) ◽  
pp. 1934578X0700201 ◽  
Author(s):  
Vietla S. Rao ◽  
Juliana L. Maia ◽  
Francisco A. Oliveira ◽  
Thelma L.G. Lemos ◽  
Mariana H. Chaves ◽  
...  
Keyword(s):  
Essential Oil ◽  
Radiant Heat ◽  
Antinociceptive Activity ◽  
Tail Flick ◽  
Hot Plate ◽  
Thermal Tests ◽  
Hot Plate Test ◽  
Thermal Pain ◽  
Tail Flick Latency ◽  
Latency Response

The chemical composition of the essential oil from Protium heptaphyllum resin was analyzed by GC/MS and the oil examined for antinociceptive activity in chemical and thermal tests. Fourteen compounds were characterized, representing 95.8% of the total essential oil, with the monoterpenes α-phellandrene (10.4%), α-terpinene (13.7%) and 1,8-cineole (58.7%) as major components. Oral administration of the essential oil (50 and 100 mg/kg) significantly inhibited chemical nociception induced by capsaicin and formalin in mice. In rats, the oil also effectively enhanced the radiant heat-induced tail-flick latency response at a dose of 100 mg/kg. However, the essential oil, at either dose, was ineffective against thermal pain in the hot-plate test.

Involvement of imidazoline and opioid receptors in the enhancement of clonidine-induced analgesia by sulfisoxazole

2010 ◽  
Vol 88 (5) ◽  
pp. 541-552 ◽  
Author(s):  
Mustufa Boxwalla ◽  
George Matwyshyn ◽  
Bhagya L. Puppala ◽  
Shridhar V. Andurkar ◽  
Anil Gulati
Keyword(s):  
Receptor Antagonist ◽  
Opioid Receptors ◽  
Analgesic Effect ◽  
Adrenergic Receptor ◽  
Area Under The Curve ◽  
Tail Flick ◽  
Imidazoline Receptors ◽  
Adrenergic Agonist ◽  
Tail Flick Latency ◽  
Dose Dependent

Clonidine, an α2-adrenergic agonist, has been demonstrated to produce significant analgesia and potentiate morphine analgesia. Endothelin (ETA) receptor antagonists have also been found to potentiate the antinociceptive response to morphine. Clonidine and ET have been reported to have cardiovascular interactions involving the sympathetic nervous system, but it is not known whether ETA receptor antagonist affects clonidine analgesia. This study examined the influence of sulfisoxazole (ETA receptor antagonist) on clonidine analgesia. Male Swiss Webster mice were used to determine antinociceptive response of drugs by measuring tail-flick latency. The effect of clonidine (0.3, 1.0, and 3.0 mg/kg, i.p.) alone or in combination with sulfisoxazole (25, 75, and 225 mg/kg, p.o.) on analgesia and body temperature was determined. Clonidine produced a dose-dependent analgesia and hypothermia. Sulfisoxazole (25, 75, and 225 mg/kg), when administered with clonidine (0.3 mg/kg), significantly potentiated (31% increase in area under the curve (AUC)) the analgesic effect of clonidine. Yohimbine (α2-adrenergic receptor antagonist) did not affect analgesic effect of clonidine plus sulfisoxazole. Idazoxan (I1-imidazoline and α2-adrenergic receptor antagonist) reduced (47% decrease in AUC) the analgesic effect of clonidine plus sulfisoxazole. Treatment with naloxone reduced (46% decrease in AUC) the analgesic effect of clonidine plus sulfisoxazole. The effect of another ETA receptor antagonist, BMS-182874 (2, 10, and 50 µg, i.c.v.) was studied, and it was found that the dose of 10 µg significantly potentiated (26% increase in AUC) the analgesic effect of clonidine. These results indicate that sulfisoxazole, an ETA receptor antagonist, potentiates the analgesic effect of clonidine, which could be mediated through I1-imidazoline receptors and opioid receptors.

scholarly journals New ibuprofen derivatives with thiazolidin-4-one scaffold with improved pharmaco-toxicological profile

2020 ◽  
Author(s):  
Ioana-Mirela Vasincu ◽  
Maria Apotrosoaei ◽  
Sandra Madalina Constantin ◽  
Maria Butnaru ◽  
Liliana Vereștiuc ◽  
...  
Keyword(s):  
Analgesic Effect ◽  
Visceral Pain ◽  
Biological Effects ◽  
Maximum Effect ◽  
Tail Flick ◽  
Paw Edema ◽  
Cell Viability Assay ◽  
Thermal Nociception ◽  
Analgesic Effects ◽  
Anti Inflammatory

Abstract Background Aryl-propionic acid derivatives with ibuprofen as representative drug are very important for therapy, being recommended especially for anti-inflammatory and analgesic effects. On other hand 1,3-thiazolidine-4-one scaffold is an important heterocycle, which is associated with different biological effects such as anti-inflammatory and analgesic, antioxidant, antiviral, antiproliferative, antimicrobial etc. The present study aimed to evaluated the toxicity degree and the anti-inflammatory and analgesic effects of new 1,3-thiazolidine-4-one derivatives of ibuprofen. Methods For evaluation the toxicity degree, cell viability assay using MTT method and acute toxicity assay on rats were applied. The carrageenan-induced paw-edema in rat was used for evaluation of the anti-inflammatory effect while for analgesic effect the tail-flick test, as thermal nociception in rats and the writhing assay, as visceral pain in mice, were used. Results The toxicological screening, in terms of cytotoxicity and toxicity degree on mice, revealed that the ibuprofen derivatives (4a-n) are non-cytotoxic at 2 µg/ml. In addition, ibuprofen derivatives reduced carrageenan-induced paw edema in rats, for most of them the maximum effect was recorded at 4 h after administration which means they have medium action latency, similar to that of ibuprofen. Moreover, for compound 4d the effect was higher than that of ibuprofen, even after 24 h of administration. The analgesic effect evaluation highlighted that 4 h showed increased pain inhibition in reference to ibuprofen in thermal (tail-flick assay) and visceral (writhing assay) nociception models. Conclusions The study revealed for ibuprofen derivatives, noted as 4 m, 4 k, 4e, 4d, a good anti-inflammatory and analgesic effect and also a safer profile compared with ibuprofen. These findings could suggest the promising potential use of them in the treatment of inflammatory pain conditions.

scholarly journals Study of analgesic property of diacerein in rat

2020 ◽  
Vol 8 (12) ◽  
pp. 4316
Author(s):  
Rajlaxmi Upadhyay ◽  
Goutam Siddhartha ◽  
Manas Ranjan Upadhyay ◽  
Trupti Rekha Swain
Keyword(s):  
Pilot Study ◽  
Analgesic Activity ◽  
Analgesic Effect ◽  
Wistar Rats ◽  
Tail Flick ◽  
Distilled Water ◽  
Spinal Level ◽  
Analgesic Drugs ◽  
Analgesic Property ◽  
Tail Flick Latency

Background: Diacerein has been known as an anti-osteoarthritic agent that is usually given along with other analgesic drugs. Still there is no evidence of the analgesic effect of diacerein alone. So this pilot study was undertaken to assess the analgesic property at supra-spinal level by using the tail-flick method.Methods: Diacerein at doses of 50, 100 and 200 mg/kg was given to Albino wistar rats weighing approximately 100-200 grams along with distilled water as placebo. All drugs were given by oral routes and the analgesic effect was evaluated using analgesiometer at baseline, 15 min, 30 min, 60 min and 120 min. Analgesic activity was measured as change in tail flick latency from baseline in animals.Results: Diacerein showed significant increase in tail flick latency and showed promising analgesic activity compared to placebo starting from 15 mins till 60 mins. However the effect persisted up to one hour only and after which it started decreasing.Conclusions: Diacerein at all the three doses possess dose dependant analgesic activity that is maximally effective up to 60 minutes.

Assessment of the Analgesic Effect of Centhaquin in Mouse Tail Flick and Hot-Plate Tests

Pharmacology ◽  
2011 ◽  
Vol 88 (5-6) ◽  
pp. 233-241 ◽  
Author(s):  
Shridhar V. Andurkar ◽  
Anil Gulati
Keyword(s):  
Analgesic Effect ◽  
Tail Flick ◽  
Hot Plate

The nitric oxide–cGMP signaling pathway plays a significant role in tolerance to the analgesic effect of morphine

2011 ◽  
Vol 89 (2) ◽  
pp. 89-95 ◽  
Author(s):  
Ercan Ozdemir ◽  
Ihsan Bagcivan ◽  
Nedim Durmus ◽  
Ahmet Altun ◽  
Sinan Gursoy
Keyword(s):  
Nitric Oxide ◽  
Analgesic Effect ◽  
Soluble Guanylate Cyclase ◽  
Morphine Tolerance ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Albino Rats ◽  
Tail Flick ◽  
Analgesic Effects ◽  
Cgmp Signaling

Although the phenomenon of opioid tolerance has been widely investigated, neither opioid nor nonopioid mechanisms are completely understood. The aim of the present study was to investigate the role of the nitric oxide (NO)–cyclic guanosine monophosphate (cGMP) pathway in the development of morphine-induced analgesia tolerance. The study was carried out on male Wistar albino rats (weighing 180–210 g; n = 126). To develop morphine tolerance, animals were given morphine (50 mg/kg; s.c.) once daily for 3 days. After the last dose of morphine was injected on day 4, morphine tolerance was evaluated. The analgesic effects of 3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole (YC-1), BAY 41-2272, S-nitroso-N-acetylpenicillamine (SNAP), NG-nitro-l-arginine methyl ester (L-NAME), and morphine were considered at 15 or 30 min intervals (0, 15, 30, 60, 90, and 120 min) by tail-flick and hot-plate analgesia tests (n = 6 in each study group). The results showed that YC-1 and BAY 41-2272, a NO-independent activator of soluble guanylate cyclase (sGC), significantly increased the development and expression of morphine tolerance, and L-NAME, a NO synthase (NOS) inhibitor, significantly decreased the development of morphine tolerance. In conclusion, these data demonstrate that the nitric oxide–cGMP signal pathway plays a pivotal role in developing tolerance to the analgesic effect of morphine.

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