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Paeoniflorin exerts analgesic and hypnotic effects via adenosine A1 receptors in a mouse neuropathic pain model.
Psychopharmacology (Berl). 2016 Jan; 233(2):281-93.P

Abstract

RATIONAL

Neuropathic pain is frequently comorbid with sleep disturbances. Paeoniflorin, a main active compound of total glucosides of paeony, has been well documented to exhibit neuroprotective bioactivity.

OBJECTIVE

The present study evaluated effects of paeoniflorin on neuropathic pain and associated insomnia and the mechanisms involved.

METHODS

The analgesic and hypnotic effects of paeoniflorin were measured by mechanical threshold and thermal latency, electroencephalogram (EEG) and electromyogram, and c-Fos expression in a neuropathic pain insomnia model.

RESULTS

The data revealed that paeoniflorin (50 or 100 mg/kg, i.p.) significantly increased the mechanical threshold and prolonged the thermal latency in partial sciatic nerve ligation (PSNL) mice. Meanwhile, paeoniflorin increased non-rapid eye movement (NREM) sleep amount and concomitantly decreased wakefulness time. However, pretreatment with l,3-dimethy-8-cyclopenthylxanthine, an adenosine A1 receptor (R, A1R) antagonist, abolished the analgesic and hypnotic effects of paeoniflorin. Moreover, paeoniflorin at 100 mg/kg failed to change mechanical threshold and thermal latency and NREM sleep in A1R knockout PSNL mice. Immunohistochemical study showed that paeoniflorin inhibited c-Fos overexpression induced by PSNL in the anterior cingulate cortex and ventrolateral periaqueductal gray.

CONCLUSIONS

The present findings indicated that paeoniflorin exerted analgesic and hypnotic effects via adenosine A1Rs and might be of potential use in the treatment of neuropathic pain and associated insomnia.

Authors+Show Affiliations

Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China. State Key Laboratory of Medical Neurobiology, Department of Pharmacology, and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai, China. Department of Neurology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.State Key Laboratory of Medical Neurobiology, Department of Pharmacology, and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai, China. liuyy@shmu.edu.cn.State Key Laboratory of Medical Neurobiology, Department of Pharmacology, and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai, China.State Key Laboratory of Medical Neurobiology, Department of Pharmacology, and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai, China.State Key Laboratory of Medical Neurobiology, Department of Pharmacology, and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai, China. Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.Department of Neurology, School of Medicine, Boston University, Boston, MA, USA.Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China. nncheng@fudan.edu.cn.State Key Laboratory of Medical Neurobiology, Department of Pharmacology, and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai, China. huangzl@fudan.edu.cn. Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China. huangzl@fudan.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26514553

Citation

Yin, Dou, et al. "Paeoniflorin Exerts Analgesic and Hypnotic Effects Via Adenosine A1 Receptors in a Mouse Neuropathic Pain Model." Psychopharmacology, vol. 233, no. 2, 2016, pp. 281-93.
Yin D, Liu YY, Wang TX, et al. Paeoniflorin exerts analgesic and hypnotic effects via adenosine A1 receptors in a mouse neuropathic pain model. Psychopharmacology (Berl). 2016;233(2):281-93.
Yin, D., Liu, Y. Y., Wang, T. X., Hu, Z. Z., Qu, W. M., Chen, J. F., Cheng, N. N., & Huang, Z. L. (2016). Paeoniflorin exerts analgesic and hypnotic effects via adenosine A1 receptors in a mouse neuropathic pain model. Psychopharmacology, 233(2), 281-93. https://doi.org/10.1007/s00213-015-4108-6
Yin D, et al. Paeoniflorin Exerts Analgesic and Hypnotic Effects Via Adenosine A1 Receptors in a Mouse Neuropathic Pain Model. Psychopharmacology (Berl). 2016;233(2):281-93. PubMed PMID: 26514553.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Paeoniflorin exerts analgesic and hypnotic effects via adenosine A1 receptors in a mouse neuropathic pain model. AU - Yin,Dou, AU - Liu,Yuan-Yuan, AU - Wang,Tian-Xiao, AU - Hu,Zhen-Zhen, AU - Qu,Wei-Min, AU - Chen,Jiang-Fan, AU - Cheng,Neng-Neng, AU - Huang,Zhi-Li, Y1 - 2015/10/29/ PY - 2015/06/04/received PY - 2015/10/05/accepted PY - 2015/10/31/entrez PY - 2015/10/31/pubmed PY - 2016/8/9/medline KW - C-Fos KW - Knockout mice KW - Sleep disturbance SP - 281 EP - 93 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 233 IS - 2 N2 - RATIONAL: Neuropathic pain is frequently comorbid with sleep disturbances. Paeoniflorin, a main active compound of total glucosides of paeony, has been well documented to exhibit neuroprotective bioactivity. OBJECTIVE: The present study evaluated effects of paeoniflorin on neuropathic pain and associated insomnia and the mechanisms involved. METHODS: The analgesic and hypnotic effects of paeoniflorin were measured by mechanical threshold and thermal latency, electroencephalogram (EEG) and electromyogram, and c-Fos expression in a neuropathic pain insomnia model. RESULTS: The data revealed that paeoniflorin (50 or 100 mg/kg, i.p.) significantly increased the mechanical threshold and prolonged the thermal latency in partial sciatic nerve ligation (PSNL) mice. Meanwhile, paeoniflorin increased non-rapid eye movement (NREM) sleep amount and concomitantly decreased wakefulness time. However, pretreatment with l,3-dimethy-8-cyclopenthylxanthine, an adenosine A1 receptor (R, A1R) antagonist, abolished the analgesic and hypnotic effects of paeoniflorin. Moreover, paeoniflorin at 100 mg/kg failed to change mechanical threshold and thermal latency and NREM sleep in A1R knockout PSNL mice. Immunohistochemical study showed that paeoniflorin inhibited c-Fos overexpression induced by PSNL in the anterior cingulate cortex and ventrolateral periaqueductal gray. CONCLUSIONS: The present findings indicated that paeoniflorin exerted analgesic and hypnotic effects via adenosine A1Rs and might be of potential use in the treatment of neuropathic pain and associated insomnia. SN - 1432-2072 UR - https://www.unboundmedicine.com/medline/citation/26514553/Paeoniflorin_exerts_analgesic_and_hypnotic_effects_via_adenosine_A1_receptors_in_a_mouse_neuropathic_pain_model_ L2 - https://dx.doi.org/10.1007/s00213-015-4108-6 DB - PRIME DP - Unbound Medicine ER -