Paeoniflorin Exerts Analgesic and Hypnotic Effects Via Adenosine A1 Receptors in a Mouse Neuropathic Pain Model

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 2015 Oct 31

PMID 26514553

Citations 21

Authors

Dou Yin

Yuan-Yuan Liu

Tian-Xiao Wang

Zhen-Zhen Hu

Wei-Min Qu

Jiang-Fan Chen

Neng-Neng Cheng

Zhi-Li Huang

Affiliations

Soon will be listed here.

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.

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References

Goldman N, Chen M, Fujita T, Xu Q, Peng W, Liu W . Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture. Nat Neurosci. 2010; 13(7):883-8. PMC: 3467968. DOI: 10.1038/nn.2562. View

Jin L, Zhang L, Xie K, Ye Y, Feng L . Paeoniflorin suppresses the expression of intercellular adhesion molecule-1 (ICAM-1) in endotoxin-treated human monocytic cells. Br J Pharmacol. 2011; 164(2b):694-703. PMC: 3188904. DOI: 10.1111/j.1476-5381.2011.01464.x. View

Cheng J, Wang C, HSU F . Paeoniflorin reverses guanethidine-induced hypotension via activation of central adenosine A1 receptors in Wistar rats. Clin Exp Pharmacol Physiol. 1999; 26(10):815-6. DOI: 10.1046/j.1440-1681.1999.03132.x. View

Liu Z, Gao X . Adenosine inhibits activity of hypocretin/orexin neurons by the A1 receptor in the lateral hypothalamus: a possible sleep-promoting effect. J Neurophysiol. 2006; 97(1):837-48. PMC: 1783688. DOI: 10.1152/jn.00873.2006. View

Wang T, Yin D, Guo W, Liu Y, Li Y, Qu W . Antinociceptive and hypnotic activities of pregabalin in a neuropathic pain-like model in mice. Pharmacol Biochem Behav. 2015; 135:31-9. DOI: 10.1016/j.pbb.2015.05.007. View

Zhuo M . Cortical excitation and chronic pain. Trends Neurosci. 2008; 31(4):199-207. DOI: 10.1016/j.tins.2008.01.003. View

Lee Y, Yaksh T . Pharmacology of the spinal adenosine receptor which mediates the antiallodynic action of intrathecal adenosine agonists. J Pharmacol Exp Ther. 1996; 277(3):1642-8. View

Li X, Ko H, Chen T, Descalzi G, Koga K, Wang H . Alleviating neuropathic pain hypersensitivity by inhibiting PKMzeta in the anterior cingulate cortex. Science. 2010; 330(6009):1400-4. DOI: 10.1126/science.1191792. View

Gong Q, Li Y, Xin W, Wei X, Cui Y, Wang J . Differential effects of adenosine A1 receptor on pain-related behavior in normal and nerve-injured rats. Brain Res. 2010; 1361:23-30. DOI: 10.1016/j.brainres.2010.09.034. View

10.

Fredholm B, IJzerman A, Jacobson K, Linden J, Muller C . International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and classification of adenosine receptors--an update. Pharmacol Rev. 2011; 63(1):1-34. PMC: 3061413. DOI: 10.1124/pr.110.003285. View

11.

Chaplan S, Bach F, Pogrel J, Chung J, Yaksh T . Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods. 1994; 53(1):55-63. DOI: 10.1016/0165-0270(94)90144-9. View

12.

Zhao X, Xu Y, Zhao Q, Chen C, Liu A, Huang Z . Curcumin exerts antinociceptive effects in a mouse model of neuropathic pain: descending monoamine system and opioid receptors are differentially involved. Neuropharmacology. 2011; 62(2):843-54. DOI: 10.1016/j.neuropharm.2011.08.050. View

13.

Baron R, Binder A, Wasner G . Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment. Lancet Neurol. 2010; 9(8):807-19. DOI: 10.1016/S1474-4422(10)70143-5. View

14.

Huang Z, Zhang Z, Qu W . Roles of adenosine and its receptors in sleep-wake regulation. Int Rev Neurobiol. 2014; 119:349-71. DOI: 10.1016/B978-0-12-801022-8.00014-3. View

15.

Sowa N, Voss M, Zylka M . Recombinant ecto-5'-nucleotidase (CD73) has long lasting antinociceptive effects that are dependent on adenosine A1 receptor activation. Mol Pain. 2010; 6:20. PMC: 2874211. DOI: 10.1186/1744-8069-6-20. View

16.

Zhang X, Chen H, Li Z, Zhang H, Xu H, Sung J . Analgesic effect of paeoniflorin in rats with neonatal maternal separation-induced visceral hyperalgesia is mediated through adenosine A(1) receptor by inhibiting the extracellular signal-regulated protein kinase (ERK) pathway. Pharmacol Biochem Behav. 2009; 94(1):88-97. DOI: 10.1016/j.pbb.2009.07.013. View

17.

OBrien E, Waxenberg L, Atchison J, Gremillion H, Staud R, McCrae C . Negative mood mediates the effect of poor sleep on pain among chronic pain patients. Clin J Pain. 2010; 26(4):310-9. DOI: 10.1097/AJP.0b013e3181c328e9. View

18.

Barros T, de Freitas L, Filho J, Nunes X, Giulietti A, de Souza G . Antinociceptive and anti-inflammatory properties of 7-hydroxycoumarin in experimental animal models: potential therapeutic for the control of inflammatory chronic pain. J Pharm Pharmacol. 2010; 62(2):205-13. DOI: 10.1211/jpp.62.02.0008. View

19.

Liu H, Zhang W, Luo X, Ye Y, Zhu X . Paeoniflorin attenuates neuroinflammation and dopaminergic neurodegeneration in the MPTP model of Parkinson's disease by activation of adenosine A1 receptor. Br J Pharmacol. 2006; 148(3):314-25. PMC: 1751566. DOI: 10.1038/sj.bjp.0706732. View

20.

Wang Q, Yue X, Qu W, Tan R, Zheng P, Urade Y . Morphine inhibits sleep-promoting neurons in the ventrolateral preoptic area via mu receptors and induces wakefulness in rats. Neuropsychopharmacology. 2013; 38(5):791-801. PMC: 3671989. DOI: 10.1038/npp.2012.244. View