12
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Characterization of the Antinociceptive Mechanisms of Khat Extract ( Catha edulis) in Mice

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          This study investigated the antinociceptive mechanisms of khat extract (100, 200, and 400 mg/kg, i.p.) in four pain models: two thermic (hot plate, tail-flick) and two chemical (acetic acid, formalin) models. Male mice were pretreated intraperitoneally (i.p.) with the opioid receptor blocker naloxone (5 mg/kg), the cholinergic antagonist atropine (2 mg/kg), the selective α 1 blocker prazosin (1 mg/kg), the dopamine D 2 antagonist haloperidol (1.5 mg/kg), or the GABA A receptor antagonist, bicuculline (1 mg/kg) 15 minutes prior to i.p. injection of khat extract (400 mg/kg). Khat extract reduced the nociceptive response of mice in the four pain tests. Naloxone significantly inhibited the antinociceptive effect of khat extract in the hot plate, tail-flick, and the first phase of formalin tests. Bicuculline significantly antagonized the antinociceptive effect of khat extract on the hot plate and tail-flick tests. Haloperidol significantly reversed the antinociceptive effect of khat extract on the tail-flick test and the first phase of formalin test. These results provide strong evidence that the antinociceptive activity of khat extract is mediated via opioidergic, GABAergic, and dopaminergic pathways. The mechanism of the antinociceptive action of khat may be linked to the different types of pain generated in animal models.

          Related collections

          Most cited references50

          • Record: found
          • Abstract: found
          • Article: not found

          Development of a rational scale to assess the harm of drugs of potential misuse.

          Drug misuse and abuse are major health problems. Harmful drugs are regulated according to classification systems that purport to relate to the harms and risks of each drug. However, the methodology and processes underlying classification systems are generally neither specified nor transparent, which reduces confidence in their accuracy and undermines health education messages. We developed and explored the feasibility of the use of a nine-category matrix of harm, with an expert delphic procedure, to assess the harms of a range of illicit drugs in an evidence-based fashion. We also included five legal drugs of misuse (alcohol, khat, solvents, alkyl nitrites, and tobacco) and one that has since been classified (ketamine) for reference. The process proved practicable, and yielded roughly similar scores and rankings of drug harm when used by two separate groups of experts. The ranking of drugs produced by our assessment of harm differed from those used by current regulatory systems. Our methodology offers a systematic framework and process that could be used by national and international regulatory bodies to assess the harm of current and future drugs of abuse.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The formalin test in mice: dissociation between inflammatory and non-inflammatory pain.

            The formalin test in mice is a valid and reliable model of nociception and is sensitive for various classes of analgesic drugs. The noxious stimulus is an injection of dilute formalin (1% in saline) under the skin of the dorsal surface of the right hindpaw. The response is the amount of time the animals spend licking the injected paw. Two distinct periods of high licking activity can be identified, an early phase lasting the first 5 min and a late phase lasting from 20 to 30 min after the injection of formalin. In order to elucidate the involvement of inflammatory processes in the two phases, we tested different classes of drugs in the two phases independently. Morphine, codeine, nefopam, and orphenadrine, as examples of centrally acting analgesics, were antinociceptive in both phases. In contrast, the non-steroid anti-inflammatory drugs indomethacin and naproxen and the steroids dexamethasone and hydrocortisone inhibited only the late phase, while acetylsalicylic acid (ASA) and paracetamol were antinociceptive in both phases. The results demonstrate that the two phases in the formalin test may have different nociceptive mechanisms. It is suggested that the early phase is due to a direct effect on nociceptors and that prostaglandins do not play an important role during this phase. The late phase seems to be an inflammatory response with inflammatory pain that can be inhibited by anti-inflammatory drugs. ASA and paracetamol seem to have actions independent of their inhibition of prostaglandin synthesis and they also have effects on non-inflammatory pain.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Cellular neuroadaptations to chronic opioids: tolerance, withdrawal and addiction.

              A large range of neuroadaptations develop in response to chronic opioid exposure and these are thought to be more or less critical for expression of the major features of opioid addiction: tolerance, withdrawal and processes that may contribute to compulsive use and relapse. This review considers these adaptations at different levels of organization in the nervous system including tolerance at the mu-opioid receptor itself, cellular tolerance and withdrawal in opioid-sensitive neurons, systems tolerance and withdrawal in opioid-sensitive nerve networks, as well as synaptic plasticity in opioid sensitive nerve networks. Receptor tolerance appears to involve enhancement of mechanisms of receptor regulation, including desensitization and internalization. Adaptations causing cellular tolerance are more complex but several important processes have been identified including upregulation of cAMP/PKA and cAMP response element-binding signalling and perhaps the mitogen activated PK cascades in opioid sensitive neurons that might not only influence tolerance and withdrawal but also synaptic plasticity during cycles of intoxication and withdrawal. The potential complexity of network, or systems adaptations that interact with opioid-sensitive neurons is great but some candidate neuropeptide systems that interact with mu-opioid sensitive neurons may play a role in tolerance and withdrawal, as might activation of glial signalling. Implication of synaptic forms of learning such as long term potentiation and long term depression in opioid addiction is still in its infancy but this ultimately has the potential to identify specific synapses that contribute to compulsive use and relapse.
                Bookmark

                Author and article information

                Contributors
                Journal
                Front Neurol
                Front Neurol
                Front. Neurol.
                Frontiers in Neurology
                Frontiers Media S.A.
                1664-2295
                02 March 2017
                2017
                : 8
                : 69
                Affiliations
                [1] 1Faculty of Pharmacy, Alexandria University , Alexandria, Egypt
                [2] 2Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University , Jeddah, Saudi Arabia
                [3] 3Faculty of Medicine, Department of Pharmacology, King Abdulaziz University , Jeddah, Saudi Arabia
                Author notes

                Edited by: Luis F. Callado, University of the Basque Country, Spain

                Reviewed by: Kabirullah Lutfy, Western University of Health Sciences, USA; Angel Josabad Alonso-Castro, Universidad de Guanajuato, Mexico

                *Correspondence: Elham A. Afify, afify001@ 123456yahoo.com

                Specialty section: This article was submitted to Neuropharmacology, a section of the journal Frontiers in Neurology

                Article
                10.3389/fneur.2017.00069
                5332354
                28316587
                646a4a9d-9612-41de-b8d8-a8511428fb0f
                Copyright © 2017 Afify, Alkreathy, Ali, Alfaifi and Khan.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 06 December 2016
                : 15 February 2017
                Page count
                Figures: 9, Tables: 0, Equations: 0, References: 59, Pages: 12, Words: 7007
                Funding
                Funded by: King Abdulaziz City for Science and Technology 10.13039/501100004919
                Award ID: Grant No. A-S-35-426
                Categories
                Neuroscience
                Original Research

                Neurology
                khat (catha edulis),hot plate,formalin,tail flick,opioidergic,dopaminergic,gabaergic
                Neurology
                khat (catha edulis), hot plate, formalin, tail flick, opioidergic, dopaminergic, gabaergic

                Comments

                Comment on this article