title: (+)-Borneol alleviates mechanical hyperalgesia in models of chronic inflammatory and neuropathic pain in mice.
abstract: Chronic pain is a major public health problem categorized as inflammatory or neuropathic, each involving impaired GABAergic control in the spinal cord of mammals. (+)-Borneol, a bicyclic monoterpene present in the essential oil of plants, is used for analgesia and anesthesia in traditional Chinese medicine. It has been reported that (+)-borneol directly potentiates GABA activity at recombinant human GABAA receptors. Although borneol has antinociceptive effect on acute pain models, little is known about its effect on chronic pain and its mechanism. Here we report that (+)-borneol has remarkable anti-hyperalgesic effects on neuropathic and inflammatory pain in animal models. Neuropathic hypersensitivity was induced by segmental spinal nerve ligation (SNL), and inflammatory hypersensitivity was induced by intraplantar (i.pl.) injection of complete Freund׳s adjuvant (CFA). Both oral administration (125, 250 or 500 mg/kg) and intrathecal injection (i.t.) (15, 30 and 60 μg) of (+)-borneol reduced mechanical hypersensitivity dose-dependently in SNL and CFA models. The anti-hyperalgesic effects of (+)-borneol were abolished by a selective GABAA receptor (GABAAR) antagonist bicuculline (i.t., at 30 min after (+)-borneol injection). Furthermore, (+)-borneol (500 mg/kg, p.o. or 60 μg, i.t.) did not influence motor function. These findings suggest that (+)-borneol may ameliorate mechanical hyperalgesia by enhancing GABAAR-mediated GABAergic transmission in the spinal cord, and could serve as a therapeutic for chronic pain.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing 211000, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing 211000, China.
authors.forename: Ying Ying
authors.initials: YY
authors.lastname: Shen
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing 211000, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing 211000, China.
authors.forename: Yu Hui
authors.initials: YH
authors.lastname: Lin
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing 211000, China.
authors.forename: Chun Xia
authors.initials: CX
authors.lastname: Luo
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing 211000, China. Electronic address: dyzhu@njmu.edu.cn.
authors.forename: Dong Ya
authors.initials: DY
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001892:Camphanes / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005620:Freund's Adjuvant / Q000009:adverse effects; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D008026:Ligation / Q000009:adverse effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D011963:Receptors, GABA-A / Q000378:metabolism
chemical_list: D001892:Camphanes; D011963:Receptors, GABA-A; D005620:Freund's Adjuvant; C022871:isoborneol
keywords: (+)-borneol; GABA(A) receptors; Inflammatory pain; Neuropathic pain