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Ameliorative effect of imperatorin in chemically induced fibromyalgia: Role of NMDA/NFkB mediated downstream signaling.

Abstract

Fibromyalgia (FM) is a chronic pain syndrome involving complex interplay of biogenic amines and NMDA receptor mediated hypersensitization of nociceptive pathways. Clinical management of FM is poorly addressed with only a few available therapeutic options. Coumarins are active phenolic molecules of natural origin found to have broad pharmacological activities. Current investigation explores the role of naturally occurring coumarin, imperatorin in mouse model of fibromyalgia. Administration of reserpine (0.5 mg/kg, s.c.) thrice at 24 h intervals induced behavioral and neurochemical alterations characteristic of fibromyalgia. Reserpine was found to induce allodynia quantified using electronic von Frey (e-VF) and pressure application measurement (PAM) test, depression as indicated by an increased duration of immobility in forced swim test (FST), decreased motor coordination and locomotor activity in inclined plane test (IPT) and open field test (OFT) respectively. Cognitive deficits were evident by an increased latency to locate hidden platform in Morris water maze (MWM) and passive avoidance test (PAT). Reserpine treatment was found to cause an increased anxiety as revealed by increased time spent in closed arm of the elevated plus maze (EPM). Furthermore, an up- regulation in NMDA and NFκB expression in the brain and spinal cord was observed in reserpine treated groups. Administration of imperatorin (10 mg/kg, i.p) for a period of 5 days ameliorated all behavioral deficits, biochemical changes and decreased expression of NMDA and NFκB in the brain and spinal cord of treated mice. These findings indicate an interplay of NMDA/NFκB modulation by imperatorin in the reserpine induced fibromyalgia in mice.

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  • Authors+Show Affiliations

    ,

    Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, India.

    ,

    Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, India.

    ,

    Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, India.

    ,

    Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar, India.

    Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, India. Electronic address: rbhatti75@gmail.com.

    Source

    Biochemical pharmacology 166: 2019 Aug pg 56-69

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    31075267

    Citation

    Kaur, Anudeep, et al. "Ameliorative Effect of Imperatorin in Chemically Induced Fibromyalgia: Role of NMDA/NFkB Mediated Downstream Signaling." Biochemical Pharmacology, vol. 166, 2019, pp. 56-69.
    Kaur A, Singh L, Singh N, et al. Ameliorative effect of imperatorin in chemically induced fibromyalgia: Role of NMDA/NFkB mediated downstream signaling. Biochem Pharmacol. 2019;166:56-69.
    Kaur, A., Singh, L., Singh, N., Bhatti, M. S., & Bhatti, R. (2019). Ameliorative effect of imperatorin in chemically induced fibromyalgia: Role of NMDA/NFkB mediated downstream signaling. Biochemical Pharmacology, 166, pp. 56-69. doi:10.1016/j.bcp.2019.05.012.
    Kaur A, et al. Ameliorative Effect of Imperatorin in Chemically Induced Fibromyalgia: Role of NMDA/NFkB Mediated Downstream Signaling. Biochem Pharmacol. 2019;166:56-69. PubMed PMID: 31075267.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Ameliorative effect of imperatorin in chemically induced fibromyalgia: Role of NMDA/NFkB mediated downstream signaling. AU - Kaur,Anudeep, AU - Singh,Lovedeep, AU - Singh,Nirmal, AU - Bhatti,Manpreet S, AU - Bhatti,Rajbir, Y1 - 2019/05/07/ PY - 2019/03/21/received PY - 2019/05/06/accepted PY - 2019/5/11/pubmed PY - 2019/5/11/medline PY - 2019/5/11/entrez KW - Fibromyalgia KW - Imperatorin KW - NFkB and NMDA KW - Reserpine SP - 56 EP - 69 JF - Biochemical pharmacology JO - Biochem. Pharmacol. VL - 166 N2 - Fibromyalgia (FM) is a chronic pain syndrome involving complex interplay of biogenic amines and NMDA receptor mediated hypersensitization of nociceptive pathways. Clinical management of FM is poorly addressed with only a few available therapeutic options. Coumarins are active phenolic molecules of natural origin found to have broad pharmacological activities. Current investigation explores the role of naturally occurring coumarin, imperatorin in mouse model of fibromyalgia. Administration of reserpine (0.5 mg/kg, s.c.) thrice at 24 h intervals induced behavioral and neurochemical alterations characteristic of fibromyalgia. Reserpine was found to induce allodynia quantified using electronic von Frey (e-VF) and pressure application measurement (PAM) test, depression as indicated by an increased duration of immobility in forced swim test (FST), decreased motor coordination and locomotor activity in inclined plane test (IPT) and open field test (OFT) respectively. Cognitive deficits were evident by an increased latency to locate hidden platform in Morris water maze (MWM) and passive avoidance test (PAT). Reserpine treatment was found to cause an increased anxiety as revealed by increased time spent in closed arm of the elevated plus maze (EPM). Furthermore, an up- regulation in NMDA and NFκB expression in the brain and spinal cord was observed in reserpine treated groups. Administration of imperatorin (10 mg/kg, i.p) for a period of 5 days ameliorated all behavioral deficits, biochemical changes and decreased expression of NMDA and NFκB in the brain and spinal cord of treated mice. These findings indicate an interplay of NMDA/NFκB modulation by imperatorin in the reserpine induced fibromyalgia in mice. SN - 1873-2968 UR - https://www.unboundmedicine.com/medline/citation/31075267/Ameliorative_effect_of_imperatorin_in_chemically_induced_fibromyalgia:_Role_of_NMDA/NFkB_mediated_downstream_signaling L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-2952(19)30176-5 DB - PRIME DP - Unbound Medicine ER -