A clinical and mechanistic study of topical bingpian-induced analgesia
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摘要
OBJECTIVE Bingpian is an almost pure chemical with a chemical composition of(+)-borneol and has been historically used as a topical analgesic in traditional Chinese medicine for millennia.However,the clinical efficacy of topical bingpian lacks stringent evidence-based clinical studies and the underlying molecular mechanisms are unclear.This study verified the analgesic efficacy of topical bingpian in humans,and elucidated the underling mechanisms in animal models of pain.METHODS The analgesic efficacy of topical bingpian was examined in a randomized,double-blind,placebo-controlled clinical study at the Shanghai Changzheng Hospital.Capsaicin,formalin,CFA or thermal caused pain/hyperalgesia were established in different mouse models,and bingpian-induced analgesia and the underlying mechanisms were studied in these models.The molecular targets of bingpian were examined by calcium imaging,patch-clamp recording and enzymatic activity assay in mouse sensory neurons or transfected HEK 293 cells.RESULTS(1)Topical application of bingpian leads to significantly greater pain relief than placebo does in a randomized,double-blind,placebo-controlled clinical study involving 122 patients with postoperative pain.(2)TRPM8 channel is the most sensitive molecular target of bingpian and mediates topical bingpian-induced analgesia in mice.(3)A downstream glutamatergic mechanism in the spinal cord contributes to topical bingpian-induced analgesia.(4)Bingpian shows mechanistic differences and advantages as a topical analgesic when compared with menthol.
OBJECTIVE Bingpian is an almost pure chemical with a chemical composition of(+)-borneol and has been historically used as a topical analgesic in traditional Chinese medicine for millennia.However,the clinical efficacy of topical bingpian lacks stringent evidence-based clinical studies and the underlying molecular mechanisms are unclear.This study verified the analgesic efficacy of topical bingpian in humans,and elucidated the underling mechanisms in animal models of pain.METHODS The analgesic efficacy of topical bingpian was examined in a randomized,double-blind,placebo-controlled clinical study at the Shanghai Changzheng Hospital.Capsaicin,formalin,CFA or thermal caused pain/hyperalgesia were established in different mouse models,and bingpian-induced analgesia and the underlying mechanisms were studied in these models.The molecular targets of bingpian were examined by calcium imaging,patch-clamp recording and enzymatic activity assay in mouse sensory neurons or transfected HEK 293 cells.RESULTS(1)Topical application of bingpian leads to significantly greater pain relief than placebo does in a randomized,double-blind,placebo-controlled clinical study involving 122 patients with postoperative pain.(2)TRPM8 channel is the most sensitive molecular target of bingpian and mediates topical bingpian-induced analgesia in mice.(3)A downstream glutamatergic mechanism in the spinal cord contributes to topical bingpian-induced analgesia.(4)Bingpian shows mechanistic differences and advantages as a topical analgesic when compared with menthol.
OBJECTIVE Bingpian is an almost pure chemical with a chemical composition of(+)-borneol and has been historically used as a topical analgesic in traditional Chinese medicine for millennia.However,the clinical efficacy of topical bingpian lacks stringent evidence-based clinical studies and the underlying molecular mechanisms are unclear.This study verified the analgesic efficacy of topical bingpian in humans,and elucidated the underling mechanisms in animal models of pain.METHODS The analgesic efficacy of topical bingpian was examined in a randomized,double-blind,placebo-controlled clinical study at the Shanghai Changzheng Hospital.Capsaicin,formalin,CFA or thermal caused pain/hyperalgesia were established in different mouse models,and bingpian-induced analgesia and the underlying mechanisms were studied in these models.The molecular targets of bingpian were examined by calcium imaging,patch-clamp recording and enzymatic activity assay in mouse sensory neurons or transfected HEK 293 cells.RESULTS(1)Topical application of bingpian leads to significantly greater pain relief than placebo does in a randomized,double-blind,placebo-controlled clinical study involving 122 patients with postoperative pain.(2)TRPM8 channel is the most sensitive molecular target of bingpian and mediates topical bingpian-induced analgesia in mice.(3)A downstream glutamatergic mechanism in the spinal cord contributes to topical bingpian-induced analgesia.(4)Bingpian shows mechanistic differences and advantages as a topical analgesic when compared with menthol.
引文