scholarly journals Spinal 5-HT7 Receptors Play an Important Role in the Antinociceptive and Antihyperalgesic Effects of Tramadol and Its Metabolite, O-Desmethyltramadol, via  Activation of Descending Serotonergic Pathways

2010 ◽  
Vol 112 (3) ◽  
pp. 696-710 ◽  
Author(s):  
Omer Yanarates ◽  
Ahmet Dogrul ◽  
Vedat Yildirim ◽  
Altan Sahin ◽  
Ali Sizlan ◽  
...  
Keyword(s):  
Potential Role ◽  
Intrathecal Injection ◽  
Radiant Heat ◽  
Tail Flick ◽  
Analgesic Drug ◽  
Mu Opioid ◽  
Pain Models ◽  
Antinociceptive Effects ◽  
Plantar Incision

Background Tramadol is an analgesic drug, and its mechanism of action is believed to be mediated by the mu-opioid receptor. A further action of tramadol has been identified as blocking the reuptake of serotonin (5-HT). One of the most recently identified subtypes of 5-HT receptor is the 5-HT7 receptor. Thus, the authors aimed to examine the potential role of serotonergic descending bulbospinal pathways and spinal 5-HT7 receptors compared with that of the 5-HT2A and 5-HT3 receptors in the antinociceptive and antihyperalgesic effects of tramadol and its major active metabolite O-desmethyltramadol (M1) on phasic and postoperative pain models. Methods Nociception was assessed by the radiant heat tail-flick and plantar incision test in male Balb-C mice (25-30 g). The serotonergic pathways were lesioned with an intrathecal injection of 5,7-dihydroxytryptamine. The selective 5-HT7, 5-HT2, and 5-HT3 antagonists; SB-269970 and SB-258719; ketanserin and ondansetron were given intrathecally. Results Systemically administered tramadol and M1 produced antinociceptive and antihyperalgesic effects. The antinociceptive effects of both tramadol and M1 were significantly diminished in 5-HT-lesioned mice. Intrathecal injection of SB-269970 (10 microg) and SB-258719 (20 microg) blocked both tramadol- and M1-induced antinociceptive and antihyperalgesic effects. Ketanserin (20 mumicrog) and ondansetron (20 microg) were unable to reverse the antinociceptive and antihyperalgesic effects of tramadol and M1. Conclusions These findings suggest that the descending serotonergic pathways and spinal 5-HT7 receptors play a crucial role in the antinociceptive and antihyperalgesic effects of tramadol and M1.

The antinociceptive effects of the tetracyclic triterpene euphol in inflammatory and neuropathic pain models: The potential role of PKCε

Neuroscience ◽  
2015 ◽  
Vol 303 ◽  
pp. 126-137 ◽  
Author(s):  
R.C. Dutra ◽  
M.A. Bicca ◽  
G.C. Segat ◽  
K.A.B.S. Silva ◽  
E.M. Motta ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Potential Role ◽  
Pain Models ◽  
Antinociceptive Effects

scholarly journals Comparison of antinociceptive effect of the antiepileptic drug gabapentin to that of various dosage combinations of gabapentin with lamotrigine and topiramate in mice and rats

2011 ◽  
Vol 02 (02) ◽  
pp. 130-136 ◽  
Author(s):  
Keshab Raj Paudel ◽  
SK Bhattacharya ◽  
GP Rauniar ◽  
BP Das
Keyword(s):  
Pain Perception ◽  
Late Phase ◽  
Antinociceptive Effect ◽  
Experimental Pain ◽  
Mechanical Hyperalgesia ◽  
Tail Flick ◽  
Hot Plate ◽  
Analgesic Effects ◽  
Pain Models ◽  
Antinociceptive Effects

ABSTRACT Introduction: Newer anticonvulsants have a neuromodulatory effect on pain perception mechanisms in a hyperexcitable and damaged nervous system. Aim: This study was designed to study the analgesic effects of gabapentin alone and in combination with lamotrigine and topiramate in experimental pain models. Materials and Methods: Adult albino mice (n = 490) weighing 20–30 g and rats (n = 130) weighing 100–200 g were injected intraperitoneally with gabapentin, lamotrigine, and topiramate alone and in different dose combinations. The hot-plate method, tail-flick method, capsaicin-induced mechanical hyperalgesia, and formalin assay were used to assess the antinociceptive effects. Results: Of the three antiepileptic drugs, when given separately, gabapentin was more efficacious than either topiramate or lamotrigine in all the pain models. Combination of 25 mg/kg gabapentin with 25 mg/kg topiramate was more efficacious (P <.05) than 50 mg/kg gabapentin alone in the capsaicin-induced mechanical hyperalgesia test. Similarly, 50 mg/kg gabapentin with 50 mg/kg topiramate or 5 mg/kg lamotrigine was more efficacious (P <.05) than 50 or 100 mg/kg gabapentin alone in late-phase formalin-induced behaviors. Conclusions: Combination of gabapentin with either lamotrigine or topiramate produced better results than gabapentin alone in capsaicin-induced mechanical hyperalgesia test and in late-phase formalin-induced behaviors.

scholarly journals Is Hippocampus Susceptible to Antinociceptive Tolerance to NSAIDs Like the Periaqueductal Grey?

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Nana Tsiklauri ◽  
Ivliane Nozadze ◽  
Gulnazi Gurtskaia ◽  
Merab G. Tsagareli
Keyword(s):  
Dorsal Hippocampus ◽  
Antinociceptive Effect ◽  
Male Rats ◽  
Opioid Antagonist ◽  
Tail Flick ◽  
Pain Models ◽  
Inflammatory Drugs ◽  
Antinociceptive Tolerance ◽  
Undesirable Feature

Emotional distress is the most undesirable feature of painful experience. Numerous studies have demonstrated the important role of the limbic system in the affective-motivational component of pain. The purpose of this paper was to examine whether microinjection of nonsteroidal anti-inflammatory drugs (NSAIDs), Clodifen, Ketorolac, and Xefocam, into the dorsal hippocampus (DH) leads to the development of antinociceptive tolerance in male rats. We found that microinjection of these NSAIDs into the DH induces antinociception as revealed by a latency increase in the tail-flick (TF) and hot plate (HP) tests compared to controls treated with saline into the DH. Subsequent tests on consecutive three days, however, showed that the antinociceptive effect of NSAIDs progressively decreased, suggesting tolerance developed to this effect of NSAIDs. Both pretreatment and posttreatment with the opioid antagonist naloxone into the DH significantly reduced the antinociceptive effect of NSAIDs in both pain models. Our data indicate that microinjection of NSAIDs into the DH induces antinociception which is mediated via the opioid system and exhibits tolerance.

New Vistas in Perioperative Pain Management

2018 ◽  
Author(s):  
Timothy Furnish ◽  
Engy Said
Keyword(s):  
Pain Management ◽  
Potential Role ◽  
Enhanced Recovery ◽  
Enhanced Recovery After Surgery ◽  
Mu Opioid ◽  
Perioperative Pain ◽  
Recovery Times ◽  
Perioperative Pain Management ◽  
Hospital Stays

The chapter “New Vistas in Perioperative Pain Management” provides an overview of analgesics for acute pain that have been recently introduced and that are in development as well as a discussion of enhanced recovery after surgery (ERAS) programs that make use of multimodal analgesic regimens. It reviews the innovation in analgesics that has focused on new formulations and uses of older compounds including oral, intravenous, and transmucosal agents. It describes the potential role of mu-opioid g-protein modulators as novel opioids with an improved adverse effect profile as well as a novel opioid with the potential for lower abuse potential. It also explains the use of analgesic regimens and pathways in ERAS programs to reduce recovery times and length of hospital stays.

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.

scholarly journals The Role of NMDARs Ligands on Antinociceptive Effects of Pregabalin in the Tail Flick Test

2015 ◽  
Vol 5 (5) ◽  
Author(s):  
Manzumeh-Shamsi Meymandi ◽  
Fariborz Keyhanfar ◽  
Omid Yazdanpanah ◽  
Gioia Heravi
Keyword(s):  
Tail Flick ◽  
Tail Flick Test ◽  
Antinociceptive Effects

The Role of Hydrogen Sulfide in the Development of Tolerance and Dependence to Morphine in Mice

2020 ◽  
pp. 1-7
Author(s):  
Zeynep Cetin ◽  
Ozgur Gunduz ◽  
Ruhan D. Topuz ◽  
Dikmen Dokmeci ◽  
Hakan C. Karadag ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Physical Dependence ◽  
Morphine Tolerance ◽  
Morphine Dependence ◽  
Tail Flick ◽  
Pain Mechanisms ◽  
Antinociceptive Effects ◽  
Synthase Inhibitor ◽  
Development Of Tolerance

<b><i>Objective:</i></b> Hydrogen sulfide is an endogenous gaseous mediator that has been indicated to have a role in pain mechanisms. In this study, we aimed to detect brain and spinal cord hydrogen sulfide levels during different phases of tolerance and dependence to morphine and to determine the effects of inhibition of endogenous hydrogen sulfide production on the development of tolerance and dependence. <b><i>Methods:</i></b> Morphine tolerance and dependence was developed by subcutaneous injection of morphine (10 mg/kg) twice daily for 12 days. Physical dependence was determined by counting the jumps for 20 min, which is a withdrawal symptom occurring after a single dose of naloxone (5 mg/kg) administered intraperitoneally (i.p.). Propargylglycine (30 mg/kg, i.p.), a cystathionine-γ-lyase inhibitor, and hydroxylamine (12.5 mg/kg, i.p.), a cystathionine-β-synthase inhibitor, were used as hydrogen sulfide synthase inhibitors. The tail-flick and hot-plate tests were used to determine the loss of antinociceptive effects of morphine and development of tolerance. <b><i>Results:</i></b> It was found that chronic and acute uses of both propargylglycine and hydroxylamine prevented the development of tolerance to morphine, whereas they had no effect on morphine dependence. Chronic and acute administrations of hydrogen sulfide synthase inhibitors did not exert any difference in hydrogen sulfide levels in brain and spinal cords of both morphine-tolerant and -dependent animals. <b><i>Conclusion:</i></b> It has been concluded that hydrogen sulfide synthase inhibitors may have utility in preventing morphine tolerance.

The potential role of green tea and its main constituent (Epigallocatechin ‐ 3‐Gallate) in pain relief: A mechanistic review

2020 ◽  
Vol 17 ◽  
Author(s):  
Sajad Sahab Negah ◽  
Hamed Ghazavi ◽  
Farzaneh Vafaee ◽  
Roghayeh Rashidi ◽  
Ahmad Reza Aminian ◽  
...  
Keyword(s):  
Pain Relief ◽  
Green Tea ◽  
Potential Role ◽  
Protective Effects ◽  
Pharmacological Activities ◽  
Green Is ◽  
Antinociceptive Effects ◽  
Phytochemical Components ◽  
And Oxidative Stress

Medicinal plants and dietary supplements may provide an effective and safe treatment for pain relief. Green tea is one of the most common beverages with many several pharmacological activities. The results of various studies have indicated that green tea possesses antinociceptive effects. Many of the protective effects of green tea in the aspect of pain relief are attributed to its antioxidant and anti-inflammatory properties. Epigallocatechin ‐3‐gallate (EGCG) as one of the major phytochemical components in green is effective in the management of pain through suppression of inflammation and oxidative stress. We reviewed the effects of green tea on pain and also, discussed its mechanisms in pain relief. This review suggests that green tea can be a safe and often effective treatment for pain.

Role of the Rostral Medial Medulla in the Development of Primary and Secondary Hyperalgesia after Incision in the Rat

2002 ◽  
Vol 96 (5) ◽  
pp. 1153-1160 ◽  
Author(s):  
Zeljko J. Bosnjak ◽  
Esther M. Pogatzki ◽  
Mark O. Urban ◽  
Timothy J. Brennan ◽  
Gerald F. Gebhart
Keyword(s):  
Visceral Pain ◽  
Ibotenic Acid ◽  
Mechanical Stimulus ◽  
Secondary Hyperalgesia ◽  
Descending Inhibition ◽  
Pain Models ◽  
Plantar Incision ◽  
Descending Influences ◽  
Heat Hyperalgesia

Background Descending influences from the rostral medial medulla (RMM) contribute to secondary hyperalgesia in persistent inflammatory, neuropathic, and visceral pain models. The current study examined if descending inhibition or facilitation from the RMM modulates primary and secondary hyperalgesia after incision in the rat hind limb. Methods Bilateral RMM lesions were produced using the soma-selective neurotoxin ibotenic acid, and the effect of RMM lesion was examined on primary and secondary hyperalgesia 5 days after a plantar or gastrocnemius incision, respectively. Results Plantar incision reduced withdrawal thresholds to von Frey filaments applied adjacent to the incision (primary punctate hyperalgesia). The withdrawal thresholds were the same in RMM-lesioned and sham-operated rats. The response frequency to a blunt mechanical stimulus after plantar incision was increased (primary nonpunctate hyperalgesia) in both groups. Nonpunctate hyperalgesia was greater in lesioned rats on postoperative day 2 only; all other measures were not different. Primary heat hyperalgesia after plantar incision was not modulated by RMM lesion. Secondary punctate hyperalgesia after gastrocnemius incision was not affected by RMM lesion. Gastrocnemius incision did not produce secondary nonpunctate or heat hyperalgesia in either RMM lesion or sham rats. Conclusion Primary and secondary hyperalgesia after an incision were not modulated by descending influence from the RMM. The lack of contribution of descending facilitatory influences from the RMM to secondary hyperalgesia after gastrocnemius incision supports the notion that incision-induced pain involves dissimilar mechanisms compared with inflammatory and neuropathic pain.

scholarly journals Analgesic and Antipyretic Activities of Methanol Extract and Its Fraction from the Root ofSchoenoplectus grossus

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Nirmal Kumar Subedi ◽  
S. M. Abdur Rahman ◽  
Mohammad Ahsanul Akbar
Keyword(s):  
Acetic Acid ◽  
Petroleum Ether ◽  
Methanol Extract ◽  
Diclofenac Sodium ◽  
Radiant Heat ◽  
Tail Flick ◽  
Dependent Manner ◽  
Tail Flick Test ◽  
Standard Drug ◽  
Pain Models

The study aims to evaluate analgesic and antipyretic activities of the methanol extract and its different fractions from root ofSchoenoplectus grossususing acetic acid induced writhing and radiant heat tail flick method of pain models in mice and yeast induced pyrexia in rats at the doses of 400 and 200 mg/kg. In acetic acid writhing test, the methanol extract, petroleum ether, and carbon tetrachloride fractions produced significant (P<0.001andP<0.05) inhibition of writhing responses in dose dependent manner. The methanol extract at 400 and 200 mg/kg being more protective with 54% and 45.45% of inhibition compared to diclofenac sodium of 56% followed by petroleum ether fractions of 49.69% and 39.39% at the same doses. The extracts did not produce any significant antinociceptive activity in tail flick test except standard morphine. When studied on yeast induced pyrexia, methanol and petroleum ether fractions significantly lowered the rectal temperature time dependently in a manner similar to standard drug paracetamol and distinctly more significant (P<0.001) after second hour. These findings suggest that the root extracts ofS. grossuspossess significant peripherally acting analgesic potential and antipyretic property. The phytochemical screening showed the presence of flavonoids, alkaloids, and tannins.

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