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Peripheral and central sites of action for anti-allodynic activity induced by the bifunctional opioid/NPFF receptors agonist BN-9 in inflammatory pain model.
Eur J Pharmacol. 2017 Oct 15; 813:122-129.EJ

Abstract

The activation of opioid and neuropeptide FF (NPFF) receptors plays important roles to modulate nociceptive signal in inflammatory pain states. Recently, BN-9 (Tyr-D. Ala-Gly-Phe-Gln-Pro-Gln-Arg-Phe-NH2) was pharmacologically characterized as a novel bifunctional agonist at both opioid and NPFF receptors. In the present study, the anti-allodynic activity and site(s) of action of BN-9 were assessed in a mouse model of carrageenan-induced inflammatory pain. In mice, BN-9 induced a dose-dependent anti-allodinic effect through opioid receptor at supraspinal or spinal level, and this effect was augmented by pretreatment with the NPFF receptor antagonist at the same level. In contrast, peripheral administration of BN-9 produced opioid receptor-mediated anti-allodynia, which was insensitive of the NPFF receptor antagonist. In addition, systemic BN-9 produced anti-allodynic effect via opioid receptors, independent of NPFF system. Therefore, these data indicate that central, peripheral or systemic administrations of BN-9 exert potent analgesic activities in inflammatory pain model via opioid receptor, and central effects of BN-9 are associated with NPFF system. Interestingly, systemic anti-allodynia of BN-9 was blocked by intraperitoneal administration of the opioid receptor antagonists, naloxone and naloxone methiodide, but not by intracerebroventricular injection of the peripherally acting opioid antagonist naloxone methiodide. Furthermore, BN-9-induced systemic anti-allodynia was reversed by intraplantar administration of naloxone, but not by peripheral administration of the NPFF receptor antagonist. Taken together, our data further suggest that systemic BN-9-induced anti-allodynic effect is mainly mediated by peripheral opioid receptors, independent of NPFF receptors.

Authors+Show Affiliations

Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, China.Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, China.Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, China.Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, China.Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, China.Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, China.Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, China.Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, China.Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, China. Electronic address: fangq@lzu.edu.cn.Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, China. Electronic address: wangrui@lzu.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28755985

Citation

Zhang, Run, et al. "Peripheral and Central Sites of Action for Anti-allodynic Activity Induced By the Bifunctional opioid/NPFF Receptors Agonist BN-9 in Inflammatory Pain Model." European Journal of Pharmacology, vol. 813, 2017, pp. 122-129.
Zhang R, Xu B, Zhang MN, et al. Peripheral and central sites of action for anti-allodynic activity induced by the bifunctional opioid/NPFF receptors agonist BN-9 in inflammatory pain model. Eur J Pharmacol. 2017;813:122-129.
Zhang, R., Xu, B., Zhang, M. N., Zhang, T., Wang, Z. L., Zhao, G., Zhao, G. H., Li, N., Fang, Q., & Wang, R. (2017). Peripheral and central sites of action for anti-allodynic activity induced by the bifunctional opioid/NPFF receptors agonist BN-9 in inflammatory pain model. European Journal of Pharmacology, 813, 122-129. https://doi.org/10.1016/j.ejphar.2017.07.044
Zhang R, et al. Peripheral and Central Sites of Action for Anti-allodynic Activity Induced By the Bifunctional opioid/NPFF Receptors Agonist BN-9 in Inflammatory Pain Model. Eur J Pharmacol. 2017 Oct 15;813:122-129. PubMed PMID: 28755985.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Peripheral and central sites of action for anti-allodynic activity induced by the bifunctional opioid/NPFF receptors agonist BN-9 in inflammatory pain model. AU - Zhang,Run, AU - Xu,Biao, AU - Zhang,Meng-Na, AU - Zhang,Ting, AU - Wang,Zi-Long, AU - Zhao,Geng, AU - Zhao,Guang-Hai, AU - Li,Ning, AU - Fang,Quan, AU - Wang,Rui, Y1 - 2017/07/27/ PY - 2017/03/05/received PY - 2017/07/04/revised PY - 2017/07/26/accepted PY - 2017/8/2/pubmed PY - 2018/5/3/medline PY - 2017/7/31/entrez KW - BN-9 KW - Bifunctional agonist KW - Inflammatory pain KW - NPFF (PubChem CID: 9854861) KW - NPVF (PubChem CID: 71451611) KW - Neuropeptide FF KW - Opioid KW - RF9 (PubChem CID: 53320361) KW - TY005 (PubChem CID: 16737673) KW - carrageenan (PubChem CID: 91972149) KW - endomorphin-2 (PubChem CID: 5311081) KW - morphine (PubChem CID: 5464110) KW - naloxone (PubChem CID: 5284596) KW - naloxone methiodide (PubChem CID: 16219719) KW - pentobarbital sodium (PubChem CID: 23676152) SP - 122 EP - 129 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 813 N2 - The activation of opioid and neuropeptide FF (NPFF) receptors plays important roles to modulate nociceptive signal in inflammatory pain states. Recently, BN-9 (Tyr-D. Ala-Gly-Phe-Gln-Pro-Gln-Arg-Phe-NH2) was pharmacologically characterized as a novel bifunctional agonist at both opioid and NPFF receptors. In the present study, the anti-allodynic activity and site(s) of action of BN-9 were assessed in a mouse model of carrageenan-induced inflammatory pain. In mice, BN-9 induced a dose-dependent anti-allodinic effect through opioid receptor at supraspinal or spinal level, and this effect was augmented by pretreatment with the NPFF receptor antagonist at the same level. In contrast, peripheral administration of BN-9 produced opioid receptor-mediated anti-allodynia, which was insensitive of the NPFF receptor antagonist. In addition, systemic BN-9 produced anti-allodynic effect via opioid receptors, independent of NPFF system. Therefore, these data indicate that central, peripheral or systemic administrations of BN-9 exert potent analgesic activities in inflammatory pain model via opioid receptor, and central effects of BN-9 are associated with NPFF system. Interestingly, systemic anti-allodynia of BN-9 was blocked by intraperitoneal administration of the opioid receptor antagonists, naloxone and naloxone methiodide, but not by intracerebroventricular injection of the peripherally acting opioid antagonist naloxone methiodide. Furthermore, BN-9-induced systemic anti-allodynia was reversed by intraplantar administration of naloxone, but not by peripheral administration of the NPFF receptor antagonist. Taken together, our data further suggest that systemic BN-9-induced anti-allodynic effect is mainly mediated by peripheral opioid receptors, independent of NPFF receptors. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/28755985/Peripheral_and_central_sites_of_action_for_anti_allodynic_activity_induced_by_the_bifunctional_opioid/NPFF_receptors_agonist_BN_9_in_inflammatory_pain_model_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(17)30499-5 DB - PRIME DP - Unbound Medicine ER -