5-HT1A receptor-mediated attenuation of heat hyperalgesia and mechanical allodynia by chrysin in mice with experimental mononeuropathy.

Abstract

BACKGROUND:

Persistent neuropathic pain poses a health problem, for which effective therapy or antidote is in dire need. This work aimed to investigate the pain-relieving effect of chrysin, a natural flavonoid with monoamine oxidase inhibitory activity, in an experimental model of neuropathic pain and elucidate mechanism(s).

METHODS:

Chronic constriction injury (CCI) was produced by loose ligation of sciatic nerve in mice. The pain-related behaviors were examined using von Frey test and Hargreaves test. The serotonin-related mechanisms were investigated by serotonin depletion with p-chlorophenylalanine (PCPA) and antagonist tests in vivo and in vitro.

RESULTS:

Repeated treatment of CCI mice with chrysin (orally, two times per day for 2 weeks) ameliorated heat hyperalgesia and mechanical allodynia in a dose-dependent fashion (3-30 mg/kg). The chrysin-triggered pain relief seems serotonergically dependent, since its antihyperalgesic and antiallodynic actions were abolished by chemical depletion of serotonin by PCPA, whereas potentiated by 5-hydroxytryptophan (a precursor of 5-HT). Consistently, chrysin-treated neuropathic mice showed enhanced levels of spinal monoamines especially 5-HT, with depressed monoamine oxidase activity. Moreover, chrysin-evoked pain relief was preferentially counteracted by 5-HT1A receptor antagonist WAY-100635 delivered systematically or spinally. In vitro, chrysin (0.1-10 nM) increased the maximum effect (Emax, shown as stimulation of [35S] GTPγS binding) of 8-OH-DPAT, a 5-HT1A agonist. Beneficially, chrysin was able to correct comorbid behavioral symptoms of depression and anxiety evoked by neuropathic pain, without causing hypertensive crisis (known as 'cheese reaction').

CONCLUSION:

These findings confirm the antihyperalgesic and antiallodynic efficacies of chrysin, with spinal 5-HT1A receptors being critically engaged.

• Authors: Jiayi Wu, Yangui Wang, Wugeng Cui, Wenhua Zhou, Xin Zhao
• Journal: Regional anesthesia and pain medicine (Reg Anesth Pain Med) Vol. 45 Issue 8 Pg. 610-619 (08 2020) ISSN: 1532-8651 [Electronic] England
• PMID: 32561651 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © American Society of Regional Anesthesia & Pain Medicine 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Flavonoids
• Htr1a protein, mouse
• Receptor, Serotonin, 5-HT1A
• chrysin

Topics

• Animals
• Disease Models, Animal
• Flavonoids
• Hot Temperature
• Hyperalgesia (drug therapy)
• Mice
• Mononeuropathies
• Receptor, Serotonin, 5-HT1A