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

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.

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Additive Antinociceptive Effects of the Selective Nav1.8 Blocker A-803467 and Selective TRPV1 Antagonists in Rat Inflammatory and Neuropathic Pain Models

Journal of Pain ◽

10.1016/j.jpain.2008.09.007 ◽

2009 ◽

Vol 10 (3) ◽

pp. 306-315 ◽

Cited By ~ 28

Author(s):

S.K. Joshi ◽

Prisca Honore ◽

Gricelda Hernandez ◽

Robert Schmidt ◽

Arthur Gomtsyan ◽

...

Keyword(s):

Neuropathic Pain ◽

Pain Models ◽

Antinociceptive Effects

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

Folia Pharmacologica Japonica ◽

10.1254/fpj.130.458 ◽

2007 ◽

Vol 130 (6) ◽

pp. 458-463

Author(s):

Katsuya Morita ◽

Naoyo Motoyama ◽

Tomoya Kitayama ◽

Norimitsu Morioka ◽

Toshihiro Dohi

Keyword(s):

Neuropathic Pain ◽

Glycine Transporter ◽

Pain Models ◽

Antinociceptive Effects

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Increase of interleukin-6 mRNA in the spinal cord following peripheral nerve injury in the rat: potential role of IL-6 in neuropathic pain

Molecular Brain Research ◽

10.1016/s0169-328x(98)00257-5 ◽

1998 ◽

Vol 62 (2) ◽

pp. 228-235 ◽

Cited By ~ 108

Author(s):

Janice L Arruda ◽

Raymond W Colburn ◽

Amy J Rickman ◽

Maria D Rutkowski ◽

Joyce A DeLeo

Keyword(s):

Spinal Cord ◽

Neuropathic Pain ◽

Peripheral Nerve ◽

Nerve Injury ◽

Interleukin 6 ◽

Peripheral Nerve Injury ◽

Potential Role

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Expression and functional role of metallothioneins I and II in the spinal cord in inflammatory and neuropathic pain models

Brain Research ◽

10.1016/j.brainres.2013.05.037 ◽

2013 ◽

Vol 1523 ◽

pp. 37-48 ◽

Cited By ~ 2

Author(s):

Aram Kwon ◽

Sang-Min Jeon ◽

Sung-Hun Hwang ◽

Jong-Heon Kim ◽

Hee-Jung Cho

Keyword(s):

Spinal Cord ◽

Neuropathic Pain ◽

Functional Role ◽

Pain Models

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Antinociceptive Activities of the Methanolic Extract of the Stem Bark ofBoswellia dalzieliiHutch. (Burseraceae) in Rats Are NO/cGMP/ATP-Sensitive-K+Channel Activation Dependent

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/6374907 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 7

Author(s):

Marius Mbiantcha ◽

Alain Ngouonpe Wembe ◽

Amadou Dawe ◽

William Yousseu Nana ◽

Gilbert Ateufack

Keyword(s):

Methylene Blue ◽

Neuropathic Pain ◽

Methanolic Extract ◽

Stem Bark ◽

Opioid Antagonist ◽

K Channel ◽

Therapeutic Effects ◽

Pain Models ◽

Antinociceptive Effects ◽

Oxide Synthase

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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Potential role of selected antiepileptics used in neuropathic pain as human GABA transporter isoform 1 (GAT1) inhibitors—Molecular docking and pharmacodynamic studies

European Journal of Pharmaceutical Sciences ◽

10.1016/j.ejps.2016.10.004 ◽

2017 ◽

Vol 96 ◽

pp. 362-372 ◽

Cited By ~ 12

Author(s):

Łukasz Fijałkowski ◽

Kinga Sałat ◽

Adrian Podkowa ◽

Paula Zaręba ◽

Alicja Nowaczyk

Keyword(s):

Neuropathic Pain ◽

Molecular Docking ◽

Potential Role ◽

Gaba Transporter

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

Current Drug Discovery Technologies ◽

10.2174/1570163817666201229121033 ◽

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.

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