title: Intrathecal lidocaine pretreatment attenuates immediate neuropathic pain by modulating Nav1.3 expression and decreasing spinal microglial activation.
abstract: BACKGROUND
  Intrathecal lidocaine reverses tactile allodynia after nerve injury, but whether neuropathic pain is attenuated by intrathecal lidocaine pretreatment is uncertain.
  
  
  METHODS
  Sixty six adult male Sprague-Dawley rats were divided into three treatment groups: (1) sham (Group S), which underwent removal of the L6 transverse process; (2) ligated (Group L), which underwent left L5 spinal nerve ligation (SNL); and (3) pretreated (Group P), which underwent L5 SNL and was pretreated with intrathecal 2% lidocaine (50 μl). Neuropathic pain was assessed based on behavioral responses to thermal and mechanical stimuli. Expression of sodium channels (Nav1.3 and Nav1.8) in injured dorsal root ganglia and microglial proliferation/activation in the spinal cord were measured on post-operative days 3 (POD3) and 7 (POD7).
  
  
  RESULTS
  Group L presented abnormal behavioral responses indicative of mechanical allodynia and thermal hyperalgesia, exhibited up-regulation of Nav1.3 and down-regulation of Nav1.8, and showed increased microglial activation. Compared with ligation only, pretreatment with intrathecal lidocaine before nerve injury (Group P), as measured on POD3, palliated both mechanical allodynia (p < 0.01) and thermal hyperalgesia (p < 0.001), attenuated Nav1.3 up-regulation (p = 0.003), and mitigated spinal microglial activation (p = 0.026) by inhibiting phosphorylation (activation) of p38 MAP kinase (p = 0.034). p38 activation was also suppressed on POD7 (p = 0.002).
  
  
  CONCLUSIONS
  Intrathecal lidocaine prior to SNL blunts the response to noxious stimuli by attenuating Nav1.3 up-regulation and suppressing activation of spinal microglia. Although its effects are limited to 3 days, intrathecal lidocaine pretreatment can alleviate acute SNL-induced neuropathic pain.
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. m725006@kmu.edu.tw
authors.forename: Kuang-I
authors.initials: KI
authors.lastname: Cheng
authors.forename: Chung-Sheng
authors.initials: CS
authors.lastname: Lai
authors.forename: Fu-Yuan
authors.initials: FY
authors.lastname: Wang
authors.forename: Hung-Chen
authors.initials: HC
authors.lastname: Wang
authors.forename: Lin-Li
authors.initials: LL
authors.lastname: Chang
authors.forename: Shung-Tai
authors.initials: ST
authors.lastname: Ho
authors.forename: Hung-Pei
authors.initials: HP
authors.lastname: Tsai
authors.forename: Aij-Li
authors.initials: AL
authors.lastname: Kwan
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage*; D000818:Animals; D015153:Blotting, Western; D005455:Fluorescent Antibody Technique; D005727:Ganglia, Spinal / Q000293:injuries; D007150:Immunohistochemistry; D007278:Injections, Spinal; D008012:Lidocaine / Q000008:administration & dosage*; D008297:Male; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000187:drug effects; D009437:Neuralgia / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000096:biosynthesis / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism
chemical_list: D000779:Anesthetics, Local; D009419:Nerve Tissue Proteins; D015222:Sodium Channels; D008012:Lidocaine