title: Nisoxetine produces local but not systemic analgesia against cutaneous nociceptive stimuli in the rat.
abstract: The aim of this study was to evaluate the local anesthetic effect of nisoxetine as infiltrative cutaneous analgesic. After rats were injected subcutaneously with nisoxetine, dose-response curves were constructed. The cutaneous anesthetic effect of nisoxetine or MK-801 (dizocilpine) was compared with lidocaine, a traditional local anesthetic. We found that nisoxetine and MK-801 acted like lidocaine and elicited dose-related cutaneous (local) anesthesia. The relative potency was nisoxetine>MK-801>lidocaine (P<0.01) as infiltrative anesthesia of skin. On an equianesthetic doses (20% effective dose [ED₂₀], ED₅₀, and ED₈₀), nisoxetine produced longer action of cutaneous anesthesia than that of lidocaine or MK-801 (P<0.01). Coadministration of nisoxetine or lidocaine with MK-801 showed an additive cutaneous anesthesia. Neither local injection of a large dose of nisoxetine, MK-801 nor lidocaine in the thigh area produced cutaneous anesthesia (data not shown). In conclusion, nisoxetine had a local anesthetic effect as infiltrative cutaneous analgesia with durations of actions longer than that of lidocaine or MK-801. That N-methyl-d-aspartate receptors may not contribute to the cutaneous (local) anesthetic effect of nisoxetine or lidocaine.
authors.affiliation: Department of Physical Therapy, China Medical University, Taichung, Taiwan.
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Chen
authors.forename: Chin-Chen
authors.initials: CC
authors.lastname: Chu
authors.forename: Yu-Chung
authors.initials: YC
authors.lastname: Chen
authors.forename: Jhi-Joung
authors.initials: JJ
authors.lastname: Wang
authors.forename: Ching-Hsia
authors.initials: CH
authors.lastname: Hung
authors.forename: Dong-Zi
authors.initials: DZ
authors.lastname: Shao
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D004058:Diffusion; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005473:Fluoxetine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007279:Injections, Subcutaneous; D007700:Kinetics; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D059226:Nociceptive Pain / Q000188:drug therapy* / Q000517:prevention & control; D009638:Norepinephrine / Q000037:antagonists & inhibitors* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012018:Reflex / Q000187:drug effects; D012867:Skin / Q000187:drug effects*
chemical_list: D000779:Anesthetics, Local; D014179:Neurotransmitter Uptake Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; D005473:Fluoxetine; C011386:nisoxetine; D016291:Dizocilpine Maleate; D009638:Norepinephrine