Effects of local lidocaine treatment before and after median nerve injury on mechanical hypersensitivity and microglia activation in rat cuneate nucleus.
This study examined the relationship between microglia activation in the cuneate nucleus (CN) and behavioral hypersensitivity after chronic constriction injury (CCI) of the median nerve. We also investigated effects of local lidocaine pre- and post-treatment on microglia activation and development of hypersensitivity in this model. By immunohistochemistry and immunoblotting, little immunoreactivity of OX-42, a microglia activation marker, was detected in the CN of normal rats. As early as 1 day after CCI, there was a significant increase in OX-42 immunoreactivity in the lesion side of CN, which reached a maximum at 14 days. Microinjection of minocycline, a microglia activation inhibitor, into the CN 1 day after CCI attenuated injury-induced behavioral hypersensitivity in a dose-dependent manner. Furthermore, the animals received 1%, 2% or 5% lidocaine 15 min prior to median nerve CCI (pre-treatment), 5h (early post-treatment) or 1 day (late post-treatment) after median nerve CCI. Pre-treatment and early post-treatment with 2% and 5% lidocaine, but not 1% lidocaine, attenuated OX-42 immunoreactivity and behavioral hypersensitivity following median nerve injury. Late post-treatment with 1%, 2%, or 5% lidocaine failed to decrease OX-42 immunoreactivity and mechanical hypersensitivity in CCI rats. In conclusion, median nerve injury-induced microglia activation in the CN modulated development of behavioral hypersensitivity. High-concentration lidocaine was effective in decreasing microglia activation in the CN and in attenuating neuropathic pain sensations at the early stage following nerve injury, when microglia had not yet been activated.
Lin
Shih-Chang
SC
Division of Allergy and Immunology, Department of Internal Medicine, Cathay General Hospital, Taipei, Taiwan, ROC.
Yeh
Jiann-Horng
JH
Chen
Chih-Li
CL
Chou
Shiu-Huey
SH
Tsai
Yi-Ju
YJ
D000779:Anesthetics, Local / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D003251:Constriction, Pathologic; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D007150:Immunohistochemistry; D008012:Lidocaine / Q000008:administration & dosage / Q000627:therapeutic use*; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D008475:Median Nerve / Q000276:immunology* / Q000473:pathology; D020423:Median Neuropathy / Q000188:drug therapy* / Q000473:pathology; D008526:Medulla Oblongata / Q000502:physiology*; D017628:Microglia / Q000187:drug effects*; D008911:Minocycline / Q000494:pharmacology; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley
D000779:Anesthetics, Local; D008012:Lidocaine; D008911:Minocycline