Echinacea purpurea against neuropathic pain: Alkamides versus polyphenols efficacy

Chemotherapy-induced neuropathy represents the main dose-limiting toxicity of several anticancer drugs, such as oxaliplatin, leading to chronic pain and an impairment of the quality of life. Echinacea purpurea n-hexane extract (EP₄ -R_E ; rich in alkamides) and butanolic extract (EP₄ -R_BU ; rich in polyphenols) have been characterized and tested in an in vivo model of oxaliplatin-induced neuropathic pain, addressing the endocannabinoid system with alkamides and counteracting the redox imbalance with polyphenols. Thermal hypersensitivity was evaluated by the Cold Plate test. EP₄ -R_E showed a dose-dependent anti-hyperalgesic profile. The extract was more effective than its main constituent, dodeca-2 E,4 E,8Z,10 E/Z-tetraenoic acid isobutylamide (18 mg kg^-1 , twofold to equimolar EP₄ -R_E 30 mg kg^-1 ), suggesting a synergy with other extract constituents. Administration of cannabinoid type 2 (CB2) receptor-selective antagonist completely blocked the anti-allodynic effect of EP₄ -R_E , differently from the antagonism of CB1 receptors. EP₄ -R_BU (30 mg kg^-1 ) exhibited anti-neuropathic properties too. The effect was mainly exerted by chicoric acid, which administered alone (123 μg kg^-1 , equimolar to EP₄ -R_BU 30 mg kg^-1 ) completely reverted oxaliplatin-induced allodynia. A synergy between different polyphenols in the extract had not been highlighted. Echinacea extracts have therapeutic potential in the treatment of neuropathic pain, through both alkamides CB2-selective activity and polyphenols protective properties.