British journal of pharmacology · 2021
Evidence for 5-HT1A receptor-mediated antiallodynic and antihyperalgesic effects of apigenin in mice suffering from mononeuropathy.
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Wu Jia-Yi, Li Ye, Li Ben-Ling, Wang Yan-Gui, Cui Wu-Geng, Zhou Wen-Hua, Zhao Xin
Аннотация
BACKGROUND AND PURPOSE: Neuropathic pain places a devastating health burden, with very few effective therapies. We investigated the potential antiallodynic and antihyperalgesic effects of apigenin, a natural flavonoid with momoamine oxidase (MAO) inhibitory activity, against neuropathic pain and investigated the mechanism(s).
EXPERIMENTAL APPROACH: The neuropathic pain model was produced by chronic constriction injury of sciatic nerves in male C57BL/6J mice, with pain-related behaviours being assayed by von Frey test and Hargreaves test. In this model the role of 5-HT and 5-HT1A receptor-related mechanisms were investigated in vivo/in vitro.
KEY RESULTS: Apigenin repeated treatment (p.o., once per day for 2 weeks), in a dose-related manner (3, 10 and 30 mg·kg-1 ), ameliorated the allodynia and hyperalgesia in chronic nerve constriction injury in mice. These effects seem dependent on neuronal 5-hydroxytryptamine, because (i) the antihyperalgesia and antiallodynia were attenuated by depletion of 5-HT with p-chlorophenylalanine and potentiated by 5-hydroxytryptophan and (ii), apigenin-treated chronic constriction injury mice caused an increased level of spinal 5-HT, associated with diminished MAO activity. In vivo administration, spinally or systematically, of the 5-HT1A antagonist WAY-100635 inhibited the apigenin-induced antiallodynia and antihyperalgesia. In vitro, apigenin acted as a positive allosteric modulator to increase the efficacy (stimulation of [35 S]GTPγS binding) of the 5-HT1A agonist 8-OH-DPAT. Apigenin attenuated neuronal changes caused by chronic constriction of the sciatic nerve in mice, without causing a hypertensive crisis.
CONCLUSION AND IMPLICATIONS: Apigenin antiallodynic and antihyperalgesic actions against neuropathic pain crucially involve spinal 5-HT1A receptors and indicate it could be used to treat neuropathic pain.
EXPERIMENTAL APPROACH: The neuropathic pain model was produced by chronic constriction injury of sciatic nerves in male C57BL/6J mice, with pain-related behaviours being assayed by von Frey test and Hargreaves test. In this model the role of 5-HT and 5-HT1A receptor-related mechanisms were investigated in vivo/in vitro.
KEY RESULTS: Apigenin repeated treatment (p.o., once per day for 2 weeks), in a dose-related manner (3, 10 and 30 mg·kg-1 ), ameliorated the allodynia and hyperalgesia in chronic nerve constriction injury in mice. These effects seem dependent on neuronal 5-hydroxytryptamine, because (i) the antihyperalgesia and antiallodynia were attenuated by depletion of 5-HT with p-chlorophenylalanine and potentiated by 5-hydroxytryptophan and (ii), apigenin-treated chronic constriction injury mice caused an increased level of spinal 5-HT, associated with diminished MAO activity. In vivo administration, spinally or systematically, of the 5-HT1A antagonist WAY-100635 inhibited the apigenin-induced antiallodynia and antihyperalgesia. In vitro, apigenin acted as a positive allosteric modulator to increase the efficacy (stimulation of [35 S]GTPγS binding) of the 5-HT1A agonist 8-OH-DPAT. Apigenin attenuated neuronal changes caused by chronic constriction of the sciatic nerve in mice, without causing a hypertensive crisis.
CONCLUSION AND IMPLICATIONS: Apigenin antiallodynic and antihyperalgesic actions against neuropathic pain crucially involve spinal 5-HT1A receptors and indicate it could be used to treat neuropathic pain.