Sciatic Nerve Intrafascicular Lidocaine Injection-induced Peripheral Neuropathic Pain: Alleviation by Systemic Minocycline Administration.
Peripheral nerve block guidance with a nerve stimulator or echo may not prevent intrafascicular injury. This study investigated whether intrafascicular lidocaine induces peripheral neuropathic pain and whether this pain can be alleviated by minocycline administration.



A total of 168 male Sprague-Dawley rats were included. In experiment 1, 2% lidocaine (0.1 mL) was injected into the left sciatic nerve. Hindpaw responses to thermal and mechanical stimuli, and sodium channel and activating transcription factor (ATF-3) expression in dorsal root ganglion (DRG) and glial cells in the spinal dorsal horn (SDH), were measured on days 4, 7, 14, 21, and 28. On the basis of the results in experiment 1, rats in experiment 2 were divided into sham, extraneural, intrafascicular, peri-injury minocycline, and postinjury minocycline groups. Behavioral responses, macrophage recruitment, expression changes of myelin basic protein and Schwann cells in the sciatic nerve, dysregulated expression of ATF-3 in the DRG, and activated glial cells in L5 SDH were assessed on days 7 and 14.



Intrafascicular lidocaine induced mechanical allodynia, downregulated Nav1.8, increased ATF-3 expression in the DRG, and activated glial cells in the SDH. Increased expression of macrophages, Schwann cells, and myelin basic protein was found in the sciatic nerve. Minocycline attenuated intrafascicular lidocaine-induced neuropathic pain and nerve damage significantly. Peri-injury minocycline was better than postinjury minocycline administration in alleviating mechanical behaviors, mitigating macrophage recruitment into the sciatic nerve, and suppressing activated microglial cells in the spinal cord.



Systemic minocycline administration alleviates intrafascicular lidocaine injection-induced peripheral nerve damage.
Departments of *Anesthesiology‡Surgery, Faculty of Medicine, College of Medicine§Surgery, Division of Plastic and Reconstructive Surgery**Microbiology and Immunology, Faculty of Medicine, College of Medicine∥Graduate Institute of Clinical Medicine, College of Medicine¶Physical Education Center#Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University†Department of Neurosurgery, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan, R.O.C.
Kuang-I
KI
Cheng
Hung-Chen
HC
Wang
Yi-Chia
YC
Wu
Kuang-Yi
KY
Tseng
Yi-Ta
YT
Chuang
Chao-Wen
CW
Chou
Ping-Luen
PL
Chen
Lin-Li
LL
Chang
Chung-Sheng
CS
Lai
D051700:Activating Transcription Factor 3 / Q000378:metabolism; D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000633:toxicity*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D039481:CD11b Antigen / Q000378:metabolism; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008012:Lidocaine / Q000633:toxicity*; D008297:Male; D008911:Minocycline / Q000627:therapeutic use*; D004676:Myelin Basic Protein / Q000378:metabolism; D009437:Neuralgia / Q000139:chemically induced* / Q000188:drug therapy*; D009457:Neuroglia / Q000378:metabolism; D010147:Pain Measurement; D051381:Rats; D012584:Sciatic Nerve / Q000187:drug effects / Q000293:injuries; D015222:Sodium Channels / Q000378:metabolism
D051700:Activating Transcription Factor 3; D000779:Anesthetics, Local; D000900:Anti-Bacterial Agents; C497108:Atf3 protein, rat; D039481:CD11b Antigen; D005904:Glial Fibrillary Acidic Protein; D004676:Myelin Basic Protein; D015222:Sodium Channels; D008012:Lidocaine; D008911:Minocycline