title: Molecular mechanisms underlying the analgesic property of intrathecal dexmedetomidine and its neurotoxicity evaluation: an in vivo and in vitro experimental study.
abstract: BACKGROUND
  Dexmedetomidine (DEX) has been used under perioperative settings as an adjuvant to enhance the analgesic property of local anesthetics by some anesthesiologists. However, the analgesic mechanisms and neurotoxicity of DEX were poorly understood. This study examined the effect of DEX alone on inflammatory pain, and it also examined the underlying molecular mechanisms of DEX in the spinal cord. Furthermore, in vivo and in vitro experiments were performed to investigate the neurotoxicity of DEX on the spinal cord and cortical neurons.
  
  
  METHODS
  This study used adult, male Kunming mice. In the acute inflammatory model, the left hind-paws of mice were intradermally injected with pH 5.0 PBS while chronic constrictive injury (CCI) of the sciatic nerve was used to duplicate the neuropathic pain condition. Thermal paw withdrawal latency and mechanical paw withdrawal threshold were tested with a radiant heat test and the Von Frey method, respectively. Locomotor activity and motor coordination were evaluated using the inverted mesh test. Western blotting examined spinal ERK1/2, p-ERK1/2, caspase-3 and β-actin expressions, while spinal c-Fos protein expression was realized with immunohistochemical staining. Hematoxylin eosin (HE) staining was used to examine the pathological impacts of intrathecal DEX on the spinal cord. DAPI (4',6-diamidino-2-phenylindole) staining was used to observe cell death under an immunofluorescence microscope.
  
  
  RESULTS
  Intra-plantar pH 5.0 PBS-induced acute pain required spinal ERK1/2 activation. Inhibition of spinal ERK1/2 signaling by intrathecal injection of DEX displayed a robust analgesia, via a α2-receptor dependent manner. The analgesic properties of DEX were validated in CCI mice. In vivo studies showed that intrathecal DEX has no significant pathological impacts on the spinal cord, and in vitro experiments indicated that DEX has potential protective effects of lidocaine-induced neural cell death.
  
  
  CONCLUSIONS
  Intrathecal injection of DEX alone or as an adjuvant might be potential for pain relief.
authors: The First Clinical College, China Medical University, Shenyang, Liaoning, People's Republic of China.
authors: Hongxing
authors: H
authors: Zhang
authors: Fang
authors: F
authors: Zhou
authors: Chen
authors: C
authors: Li
authors: Min
authors: M
authors: Kong
authors: He
authors: H
authors: Liu
authors: Peng
authors: P
authors: Zhang
authors: Song
authors: S
authors: Zhang
authors: Junli
authors: J
authors: Cao
authors: Licai
authors: L
authors: Zhang
authors: Hong
authors: H
authors: Ma
mesh_terms: D000700:Analgesics / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D000818:Animals; D015153:Blotting, Western; D020927:Dexmedetomidine / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009420:Nervous System / Q000187:drug effects; D010146:Pain / Q000188:drug therapy
chemical_list: D000700:Analgesics; D020927:Dexmedetomidine