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.

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 Effects of peripheral FAAH blockade on NTG-induced hyperalgesia—evaluation of URB937 in an animal model of migraine

Cephalalgia ◽  
2015 ◽  
Vol 35 (12) ◽  
pp. 1065-1076 ◽  
Author(s):  
R Greco ◽  
T Bandiera ◽  
AS Mangione ◽  
C Demartini ◽  
F Siani ◽  
...  
Keyword(s):  
Animal Model ◽  
Antinociceptive Effect ◽  
Acid Amide ◽  
Male Rats ◽  
Tail Flick ◽  
Tail Flick Test ◽  
Brain Nuclei ◽  
Nociceptive Responses ◽  
Fos Expression ◽  
Baseline Conditions

Background Systemic nitroglycerin (NTG) activates brain nuclei involved in nociceptive transmission as well as in neuroendocrine and autonomic functions in rats. These changes are considered relevant for migraine because NTG consistently provokes spontaneous-like migraine attacks in migraineurs. Several studies have suggested a relationship between the endocannabinoid levels and pain mediation in migraine. URB937, a peripheral inhibitor of fatty acid amide hydrolase (FAAH)—the enzyme that degrades anandamide, produces analgesia in animal models of pain, but there is no information on its effects in migraine. Aim We evaluated whether URB937 alters nociceptive responses in the animal model of migraine based on NTG administration in male rats, using the tail flick test and the plantar and orofacial formalin tests, under baseline conditions and after NTG administration. Furthermore, we investigated whether URB937 affects NTG-induced c-Fos expression in the brain. Results During the tail flick test, URB937 showed an antinociceptive effect in baseline conditions and it blocked NTG-induced hyperalgesia. URB937 also proved effective in counteracting NTG-induced hyperalgesia during both the plantar and orofacial formalin tests. Mapping of brain nuclei activated by NTG indicates that URB937 significantly reduces c-Fos expression in the nucleus trigeminalis caudalis and the locus coeruleus. Conclusions The data suggest that URB937 is capable of changing, probably via indirect mechanisms, the functional status of central structures that are important for pain transmission in an animal model of migraine.

scholarly journals Blockade of Adrenal Medulla-Derived Epinephrine Potentiates Bee Venom-Induced Antinociception in the Mouse Formalin Test: Involvement of Peripheralβ-Adrenoceptors

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Suk-Yun Kang ◽  
Dae-Hyun Roh ◽  
Hyun-Woo Kim ◽  
Ho-Jae Han ◽  
Alvin J. Beitz ◽  
...  
Keyword(s):  
Adrenal Medulla ◽  
Formalin Test ◽  
Late Phase ◽  
Antinociceptive Effect ◽  
Bee Venom ◽  
Pain Models ◽  
Adrenergic Antagonists ◽  
Novel Strategy ◽  
Chronic Pain Conditions

The injection of diluted bee venom (DBV) into an acupoint has been used traditionally in eastern medicine to treat a variety of inflammatory chronic pain conditions. We have previously shown that DBV had a potent antinociceptive efficacy in several rodent pain models. However, the peripheral mechanisms underlying DBV-induced antinociception remain unclear. The present study was designed to investigate the role of peripheral epinephrine on the DBV-induced antinociceptive effect in the mouse formalin assay. Adrenalectomy significantly enhanced the antinociceptive effect of DBV during the late phase of the formalin test, while chemical sympathectomy had no effect. Intraperitoneal injection of epinephrine blocked this adrenalectomy-induced enhancement of the DBV-induced antinociceptive effect. Moreover, injection of a phenylethanolamine N-methyltransferase (PNMT) inhibitor enhanced the DBV-induced antinociceptive effect. Administration of nonselectiveβ-adrenergic antagonists also significantly potentiated this DBV-induced antinociception, in a manner similar to adrenalectomy. These results demonstrate that the antinociceptive effect of DBV treatment can be significantly enhanced by modulation of adrenal medulla-derived epinephrine and this effect is mediated by peripheralβ-adrenoceptors. Thus, DBV acupoint stimulation in combination with inhibition of peripheralβ-adrenoceptors could be a potentially novel strategy for the management of inflammatory pain.

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 Two strategies used to solve a navigation task: A different use of the hippocampus by males and females? A preliminary study in rats

2018 ◽  
Vol 39 (2) ◽  
pp. 319-339 ◽  
Author(s):  
Ferran Lugo ◽  
Marta N. Torres ◽  
V.D. Chamizo
Keyword(s):  
Dorsal Hippocampus ◽  
Female Rats ◽  
Male Rats ◽  
Males And Females ◽  
Preliminary Study ◽  
Types Of Information ◽  
Landmark Learning ◽  
Source Of Information ◽  
Geometry Learning

AbstractThere is abundant research (both in rodents and in humans) showing that males and females often use different types of information in spatial navigation. Males prefer geometry as a source of information, whereas females tend to focus on landmarks (which are often near to a goal objects). However, when considering the role of the hippocampus, the research focuses primarily on males only. In the present study, based on Rodríguez, Torres, Mackintosh, and Chamizo’s (2010, Experiment 2) navigation protocol, we conducted two experiments, one with males and another with females, in order to tentatively evaluate the role of the dorsal hippocampus in the acquisition of two tasks: one based on landmark learning and the alternate one on local pool-geometry learning. Both when landmark learning and when geometry learning, Sham male rats learned significantly faster than Lesion male animals. This was not the case with female rats in geometry learning. These results suggest that the dorsal hippocampus could play an important role in males only.

scholarly journals Methanolic Extract ofClinacanthus nutansExerts Antinociceptive Activity via the Opioid/Nitric Oxide-Mediated, but cGMP-Independent, Pathways

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Mohammad Hafiz Abdul Rahim ◽  
Zainul Amiruddin Zakaria ◽  
Mohd Hijaz Mohd Sani ◽  
Maizatul Hasyima Omar ◽  
Yusnita Yakob ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Antinociceptive Effect ◽  
Soluble Guanylyl Cyclase ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Antinociceptive Activity ◽  
Opioid Antagonist ◽  
Clinacanthus Nutans ◽  
Synthase Inhibitor

The objectives of the present study were to determine the mechanisms of antinociceptive effect of methanol extract ofClinacanthus nutans(Acanthaceae) leaves (MECN) using various animal nociceptive models. The antinociceptive activity of orally administered 10% DMSO, 100 mg/kg acetylsalicylic acid (ASA), 5 mg/kg morphine, or MECN (100, 250, and 500 mg/kg) was determined using the acetic acid-induced abdominal constriction (ACT), formalin-induced paw licking (FT), and hot plate tests (HPT). The role of opioid and nitric oxide/cyclic guanosine monophosphate (NO/cGMP) systems was also investigated. The results showed that MECN produced a significant (p<0.05) antinociceptive response in all nociceptive models with the recordedED50value of 279.3 mg/kg for the ACT, while, for the early and late phases of the FT, the value was >500 mg/kg or 227.7 mg/kg, respectively. This antinociceptive activity was fully antagonized by naloxone (a nonselective opioid antagonist) but was partially reversed byL-arginine (L-arg; a nitric oxide [NO] precursor), Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME; an NO synthase inhibitor), or their combinations thereof. In contrast, 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ; a soluble guanylyl cyclase inhibitor) enhanced the extract’s antinociception. UHPLC analysis revealed the presence of several flavonoid-based compounds with antinociceptive action. In conclusion, MECN exerted the peripherally and centrally mediated antinociceptive activity via the modulation of the opioid/NO-mediated, but cGMP-independent, systems.

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.

scholarly journals Non-steroidal Anti-inflammatory Drugs in Tonic, Phasic and Inflammatory Mouse Models

Drug Research ◽  
2019 ◽  
Vol 69 (10) ◽  
pp. 572-578 ◽  
Author(s):  
Hugo F. Miranda ◽  
Viviana Noriega ◽  
Fernando Sierralta ◽  
Paula Poblete ◽  
Nicolas Aranda ◽  
...  
Keyword(s):  
Phase Ii ◽  
Antinociceptive Effect ◽  
Tail Flick ◽  
Tail Flick Test ◽  
Principal Mechanism ◽  
Writhing Test ◽  
A Value ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Dose Dependent

AbstractThe principal mechanism of action of non-steroidal anti-inflammatory drugs (NSAIDs) is the inhibition of ciclooxigenases. In this study was evaluated if NSAIDs could induce antinociceptive differences according to the type of murine pain model. Male mice were injected intraperitoneally with meloxicam, diclofenac, piroxicam, metamizol, ibuprofen, naproxen and paracetamol in the writhing, tail flick and formalin orofacial tests and dose-response were analyzed to obtain the ED50 of each drugs. Administration of NSAIDs produced in a dose-dependent antinociception with different potency in the tests. The relative potency of NSAIDs among the tests shows a value of 5.53 in the orofacial formalin test in phase I and 6.34 in phase II between meloxicam and paracetamol; of 7.60 in the writhing test between meloxicam and paracetamol and of 8.46 in the tail flick test between ibuprofen and paracetamol. If the comparison is made for each NSAID in the different tests, the minimum value was 0.01 for between writhing and phase II of the orofacial formalin. Meanwhile, the highest power ratio was 11.71 for diclofenac between writhing and tail flick tests. In conclusion, the results suggests that intraperitoneal NSAIDs administration induce antinociceptive activity depending on the type of pain. The results support that NSAIDs administration, induce a wide variety of antinociceptive effect, depending on the type of pain. This suggest the participation of different mechanisms of action that can be added to the simple inhibition of COXs controlled by NSAIDs.

scholarly journals Antinociception Following Implantation of AtT-20 and Genetically Modified AtT-20/hENK Cells in Rat Spinal Cord

1993 ◽  
Vol 4 (1) ◽  
pp. 15-26 ◽  
Author(s):  
Hope H. Wu ◽  
Steven C. McLoon ◽  
George L. Wilcox
Keyword(s):  
Spinal Cord ◽  
Antinociceptive Effect ◽  
Alternative Therapy ◽  
Immunohistochemical Analysis ◽  
Opioid Antagonist ◽  
Control Group ◽  
Tail Flick ◽  
Rat Spinal Cord ◽  
Adrenergic Agonist ◽  
Spinal Subarachnoid Space

AtT-20 cells, which produceß-endorphin, and AtT-20/hENK cells, which are AtT-20 cells transfected with a proenkephalin gene, were implanted in the rat spinal subarachnoid space in an effort to produce an antinociceptive effect. Host rats were tested for antinociceptive activity by standard nociceptive tests, tail flick and hot plate. Although cell implants had minimal effect on the basal response to thermal nociceptive stimuli, administration of theß2-adrenergic agonist isoproterenol produced antinociception in the cell-implanted group but not in the control group. The antinociceptive effect of isoproterenol was dose-related and could be blocked by the opioid antagonist naloxone. Immunohistochemical analysis of spinal cords revealed the presence of enkephalin-negative cells surrounding the spinal cord of rats receiving AtT-20 cell implants, and enkephalinpositive cells surrounding the spinal cord of rats. receiving AtT-20/hENK cell implants. These results suggest that opioid-releasing cells implanted around rat spinal cord can produce antinociception and may provide an alternative therapy for chronic pain.

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