Antinociceptive effects of glycine transporter inhibitors in neuropathic pain models in mice

Boswellia dalzielii (B. dalzielii)is traditionally used in the treatment of rheumatism, pain, and inflammation. The present investigation evaluates the property and possible mechanism of action of the methanolic extract ofB. dalzielii(BDME) on inflammatory and neuropathic pain models. Effects of BDME (250 and 500 mg/kg), orally administered, were verified in mechanical hypernociception induced by LPS or PGE2. Mechanical hyperalgesia, cold allodynia, and heat hyperalgesia were used in vincristine-induced neuropathic pain. NW-nitro-L-arginine methyl ester (inhibitor of nitric oxide synthase), glibenclamide (ATP-sensitive potassium channel blocker), methylene blue (cGMP blocker), or naloxone (opioid antagonist receptor) has been used to evaluate the therapeutic effects of BDME on PGE2-induced hyperalgesia. Chemical profile of BDME was determined by using HPLC-XESI-PDA/MS. BDME showed significant antinociceptive effects in inflammatory pain caused by LPS and PGE2. The extract also significantly inhibited neuropathic pain induced by vincristine. The antinociceptive property of BDME in PGE2model was significantly blocked by L-NAME, glibenclamide, methylene blue, or naloxone. The present work reveals the antinociceptive activities of BDME both in inflammatory and in neuropathic models of pain. This plant extract may be acting firstly by binding to opioid receptors and secondly by activating the NO/cGMP/ATP-sensitive-K+channel pathway.

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Spinal Antiallodynia Action of Glycine Transporter Inhibitors in Neuropathic Pain Models in Mice

Journal of Pharmacology and Experimental Therapeutics ◽

10.1124/jpet.108.136267 ◽

2008 ◽

Vol 326 (2) ◽

pp. 633-645 ◽

Cited By ~ 85

Author(s):

Katsuya Morita ◽

Naoyo Motoyama ◽

Tomoya Kitayama ◽

Norimitsu Morioka ◽

Koki Kifune ◽

...

Keyword(s):

Neuropathic Pain ◽

Glycine Transporter ◽

Pain Models

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

Neuroscience ◽

10.1016/j.neuroscience.2015.06.051 ◽

2015 ◽

Vol 303 ◽

pp. 126-137 ◽

Cited By ~ 30

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

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Curcumin exerts antinociceptive effects in a mouse model of neuropathic pain: Descending monoamine system and opioid receptors are differentially involved

Neuropharmacology ◽

10.1016/j.neuropharm.2011.08.050 ◽

2012 ◽

Vol 62 (2) ◽

pp. 843-854 ◽

Cited By ~ 87

Author(s):

Xin Zhao ◽

Ying Xu ◽

Qing Zhao ◽

Chang-Rui Chen ◽

Ai-Ming Liu ◽

...

Keyword(s):

Neuropathic Pain ◽

Mouse Model ◽

Opioid Receptors ◽

Antinociceptive Effects

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Effects of alpha 7 positive allosteric modulators in murine inflammatory and chronic neuropathic pain models

Neuropharmacology ◽

10.1016/j.neuropharm.2012.08.022 ◽

2013 ◽

Vol 65 ◽

pp. 156-164 ◽

Cited By ~ 49

Author(s):

Kelen Freitas ◽

Sudeshna Ghosh ◽

F. Ivy Carroll ◽

Aron H. Lichtman ◽

M. Imad Damaj

Keyword(s):

Neuropathic Pain ◽

Allosteric Modulators ◽

Chronic Neuropathic Pain ◽

Pain Models ◽

Positive Allosteric Modulators ◽

Alpha 7

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Neuropathic pain models in the development of analgesic drugs

Scandinavian Journal of Pain ◽

10.1016/j.sjpain.2011.06.003 ◽

2011 ◽

Vol 2 (4) ◽

pp. 172-177 ◽

Cited By ~ 15

Author(s):

Per Hartvig Honoré ◽

Anna Basnet ◽

Laila Eljaja ◽

Pernille Kristensen ◽

Lene Munkholm Andersen ◽

...

Keyword(s):

Neuropathic Pain ◽

Animal Models ◽

Nerve Injury ◽

Clinical Manifestations ◽

Pharmacological Intervention ◽

Special Focus ◽

Surgical Performance ◽

Neuropathic Pain Syndrome ◽

Pain Models ◽

Rats And Mice

AbstractIntroductionAnimal disease models are predictive for signs seen in disease. They may rarely mimic all signs in a specific disease in humans with respect to etiology, cause or development. Several models have been developed for different pain states and the alteration of behavior has been interpreted as a response to external stimulus or expression of pain or discomfort. Considerable attention must be paid not to interpret other effects such as somnolence or motor impairment as a pain response and similarly not to misinterpret the response of analgesics.Neuropathic pain is caused by injury or disease of the somatosensory system. The clinical manifestations of neuropathic pain vary including both stimulus-evoked and non-stimulus evoked (spontaneous) symptoms. By pharmacological intervention, the threshold for allodynia and hyperalgesia in the various pain modalities can be modulated and measured in animals and humans. Animal models have been found most valuable in studies on neuropathic pain and its treatment.Aim of the studyWith these interpretation problems in mind, the present text aims to describe the most frequently used animal models of neuropathic pain induced by mechanical nerve injury.MethodsThe technical surgical performance of these models is described as well as pain behavior based on the authors own experience and from a literature survey.ResultsNerve injury in the hind limb of rats and mice is frequently used in neuropathic pain models and the different types of lesion may afford difference in the spread and quality of the pain provoked. The most frequently used models are presented, with special focus on the spared nerve injury (SNI) and the spinal nerve ligation/transection (SNL/SNT) models, which are extensively used and validated in rats and mice. Measures of mechanical and thermal hypersensitivity with von Frey filaments and Hargreaves test, respectively, are described and shown in figures.ConclusionsA number of animal models have been developed and described for neuropathic pain showing predictive value in parallel for both humans and animals. On the other hand, there are still large knowledge gaps in the pathophysiologic mechanisms for the development, maintenance and progression of the neuropathic pain syndromeImplicationsBetter understanding of pathogenic mechanisms of neuropathic pain in animal models may support the search for new treatment paradigms in patients with complex neuropathic pain conditions

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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

Journal of Neurosciences in Rural Practice ◽

10.4103/0976-3147.83577 ◽

2011 ◽

Vol 02 (02) ◽

pp. 130-136 ◽

Cited By ~ 9

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.

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Monoaminergic and Opioidergic Modulation of Brainstem Circuits: New Insights Into the Clinical Challenges of Pain Treatment?

Frontiers in Pain Research ◽

10.3389/fpain.2021.696515 ◽

2021 ◽

Vol 2 ◽

Author(s):

Isaura Tavares ◽

José Tiago Costa-Pereira ◽

Isabel Martins

Keyword(s):

Neuropathic Pain ◽

Pain Control ◽

Pain Treatment ◽

Reticular Nucleus ◽

Serotoninergic System ◽

High Plasticity ◽

Descending Facilitation ◽

Pain Models ◽

Dual Action ◽

Control Circuits

The treatment of neuropathic pain remains a clinical challenge. Analgesic drugs and antidepressants are frequently ineffective, and opioids may induce side effects, including hyperalgesia. Recent results on brainstem pain modulatory circuits may explain those clinical challenges. The dual action of noradrenergic (NA) modulation was demonstrated in animal models of neuropathic pain. Besides the well-established antinociception due to spinal effects, the NA system may induce pronociception by directly acting on brainstem pain modulatory circuits, namely, at the locus coeruleus (LC) and medullary dorsal reticular nucleus (DRt). The serotoninergic system also has a dual action depending on the targeted spinal receptor, with an exacerbated activity of the excitatory 5-hydroxytryptamine 3 (5-HT3) receptors in neuropathic pain models. Opioids are involved in the modulation of descending modulatory circuits. During neuropathic pain, the opioidergic modulation of brainstem pain control areas is altered, with the release of enhanced local opioids along with reduced expression and desensitization of μ-opioid receptors (MOR). In the DRt, the installation of neuropathic pain increases the levels of enkephalins (ENKs) and induces desensitization of MOR, which may enhance descending facilitation (DF) from the DRt and impact the efficacy of exogenous opioids. On the whole, the data discussed in this review indicate the high plasticity of brainstem pain control circuits involving monoaminergic and opioidergic control. The data from studies of these neurochemical systems in neuropathic models indicate the importance of designing drugs that target multiple neurochemical systems, namely, maximizing the antinociceptive effects of antidepressants that inhibit the reuptake of serotonin and noradrenaline and preventing desensitization and tolerance of MOR at the brainstem.

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