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Piromelatine exerts antinociceptive effect via melatonin, opioid, and 5HT1A receptors and hypnotic effect via melatonin receptors in a mouse model of neuropathic pain.
Psychopharmacology (Berl). 2014 Oct; 231(20):3973-85.P

Abstract

RATIONALE

An effective and safe treatment of insomnia in patients with neuropathic pain remains an unmet need. Melatonin and its analogs have been shown to have both analgesic and hypnotic effects; however, capacity of them on sleep disturbance with neuropathic pain as well as the precise mechanism is unclear.

OBJECTIVE

The present study evaluated effects of piromelatine, a novel melatonin receptor agonist, on sleep disturbance in a neuropathic pain-like condition as well as the underlying mechanisms.

METHODS

A mouse model of chronic neuropathic pain induced by partial sciatic nerve ligation (PSL) was employed. The antinociceptive and hypnotic effects of piromelatine were evaluated by measurement of thermal hyperalgesia, mechanical allodynia, and electroencephalogram (EEG) recordings in PSL mice. Pharmacological approaches were used to clarify the mechanisms of action of piromelatine.

RESULTS

PSL significantly lowered thermal and mechanical latencies and decreased non-rapid eye movement (NREM) sleep, and PSL mice exhibited sleep fragmentation. Treatment with 25, 50, or 100 mg/kg of piromelatine significantly prolonged thermal and mechanical latencies and increased NREM sleep. Moreover, the antinociceptive effect of piromelatine was prevented by melatonin antagonist luzindole, opioid receptor antagonist naloxone, or 5HT1A receptor antagonist WAY-100635. The hypnotic effect of piromelatine was blocked by luzindole but neither by naloxone nor WAY-100635.

CONCLUSIONS

These data indicate that piromelatine is an effective treatment for both neuropathic pain and sleep disturbance in PSL mice. The antinociceptive effect of piromelatine is likely mediated by melatonin, opioid, and 5HT1A receptors; however, the hypnotic effect of piromelatine appears to be mediated by melatonin receptors.

Authors+Show Affiliations

Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

24700387

Citation

Liu, Yuan-Yuan, et al. "Piromelatine Exerts Antinociceptive Effect Via Melatonin, Opioid, and 5HT1A Receptors and Hypnotic Effect Via Melatonin Receptors in a Mouse Model of Neuropathic Pain." Psychopharmacology, vol. 231, no. 20, 2014, pp. 3973-85.
Liu YY, Yin D, Chen L, et al. Piromelatine exerts antinociceptive effect via melatonin, opioid, and 5HT1A receptors and hypnotic effect via melatonin receptors in a mouse model of neuropathic pain. Psychopharmacology (Berl). 2014;231(20):3973-85.
Liu, Y. Y., Yin, D., Chen, L., Qu, W. M., Chen, C. R., Laudon, M., Cheng, N. N., Urade, Y., & Huang, Z. L. (2014). Piromelatine exerts antinociceptive effect via melatonin, opioid, and 5HT1A receptors and hypnotic effect via melatonin receptors in a mouse model of neuropathic pain. Psychopharmacology, 231(20), 3973-85. https://doi.org/10.1007/s00213-014-3530-5
Liu YY, et al. Piromelatine Exerts Antinociceptive Effect Via Melatonin, Opioid, and 5HT1A Receptors and Hypnotic Effect Via Melatonin Receptors in a Mouse Model of Neuropathic Pain. Psychopharmacology (Berl). 2014;231(20):3973-85. PubMed PMID: 24700387.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Piromelatine exerts antinociceptive effect via melatonin, opioid, and 5HT1A receptors and hypnotic effect via melatonin receptors in a mouse model of neuropathic pain. AU - Liu,Yuan-Yuan, AU - Yin,Dou, AU - Chen,Li, AU - Qu,Wei-Min, AU - Chen,Chang-Rui, AU - Laudon,Moshe, AU - Cheng,Neng-Neng, AU - Urade,Yoshihiro, AU - Huang,Zhi-Li, Y1 - 2014/04/04/ PY - 2013/11/17/received PY - 2014/03/04/accepted PY - 2014/4/5/entrez PY - 2014/4/5/pubmed PY - 2015/10/13/medline SP - 3973 EP - 85 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 231 IS - 20 N2 - RATIONALE: An effective and safe treatment of insomnia in patients with neuropathic pain remains an unmet need. Melatonin and its analogs have been shown to have both analgesic and hypnotic effects; however, capacity of them on sleep disturbance with neuropathic pain as well as the precise mechanism is unclear. OBJECTIVE: The present study evaluated effects of piromelatine, a novel melatonin receptor agonist, on sleep disturbance in a neuropathic pain-like condition as well as the underlying mechanisms. METHODS: A mouse model of chronic neuropathic pain induced by partial sciatic nerve ligation (PSL) was employed. The antinociceptive and hypnotic effects of piromelatine were evaluated by measurement of thermal hyperalgesia, mechanical allodynia, and electroencephalogram (EEG) recordings in PSL mice. Pharmacological approaches were used to clarify the mechanisms of action of piromelatine. RESULTS: PSL significantly lowered thermal and mechanical latencies and decreased non-rapid eye movement (NREM) sleep, and PSL mice exhibited sleep fragmentation. Treatment with 25, 50, or 100 mg/kg of piromelatine significantly prolonged thermal and mechanical latencies and increased NREM sleep. Moreover, the antinociceptive effect of piromelatine was prevented by melatonin antagonist luzindole, opioid receptor antagonist naloxone, or 5HT1A receptor antagonist WAY-100635. The hypnotic effect of piromelatine was blocked by luzindole but neither by naloxone nor WAY-100635. CONCLUSIONS: These data indicate that piromelatine is an effective treatment for both neuropathic pain and sleep disturbance in PSL mice. The antinociceptive effect of piromelatine is likely mediated by melatonin, opioid, and 5HT1A receptors; however, the hypnotic effect of piromelatine appears to be mediated by melatonin receptors. SN - 1432-2072 UR - https://www.unboundmedicine.com/medline/citation/24700387/Piromelatine_exerts_antinociceptive_effect_via_melatonin_opioid_and_5HT1A_receptors_and_hypnotic_effect_via_melatonin_receptors_in_a_mouse_model_of_neuropathic_pain_ L2 - https://dx.doi.org/10.1007/s00213-014-3530-5 DB - PRIME DP - Unbound Medicine ER -