Molecular Mechanisms Underlying the Analgesic Property of Intrathecal Dexmedetomidine and Its Neurotoxicity Evaluation: An In Vivo and In Vitro Experimental Study

PLoS ONE

Volumn 8, Issue 2, 2013, Pages

  Zhang, Hongxing ^a   Zhou, Fang ^a,b   Li, Chen ^b   Kong, Min ^b   Liu, He ^a,b   Zhang, Peng ^b   Zhang, Song ^b   Cao, Junli ^b   Zhang, Licai ^b   Ma, Hong ^a  

^a CHINA MEDICAL UNIVERSITY   (China)

^b XUZHOU MEDICAL UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

4',6 DIAMIDINO 2 PHENYLINDOLE; ALPHA 2 ADRENERGIC RECEPTOR; BETA ACTIN; CASPASE 3; DEXMEDETOMIDINE; MITOGEN ACTIVATED PROTEIN KINASE 1; PROTEIN C FOS;

ALLODYNIA; ANALGESIC ACTIVITY; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; DRUG DOSE COMPARISON; EMBRYO; ENZYME ACTIVATION; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; EXPERIMENTAL STUDY; HISTOPATHOLOGY; HYPERALGESIA; IMMUNOFLUORESCENCE MICROSCOPY; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATORY PAIN; LOCOMOTION; MALE; MOLECULAR DYNAMICS; MOTOR COORDINATION; MOUSE; NERVE CELL NECROSIS; NEUROPATHIC PAIN; NEUROPROTECTION; NEUROTOXICITY; NONHUMAN; PAW EDEMA; RAT; TOXICITY TESTING; WESTERN BLOTTING;

ANALGESICS; ANIMALS; BLOTTING, WESTERN; DEXMEDETOMIDINE; IMMUNOHISTOCHEMISTRY; INJECTIONS, SPINAL; MALE; MICE; NERVOUS SYSTEM; PAIN;

EID: 84873586243     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0055556     Document Type: Article

References (30)

1. Grosu I, Lavand'homme P, (2010) Use of dexmedetomidine for pain control. F1000 Med Rep 2: 90.
2. Brummett CM, Trivedi KA, Dubovoy AV, Berland DW, (2009) Dexmedetomidine as a novel therapeutic for postoperative pain in a patient treated with buprenorphine. J Opioid Manag 5: 175-179.
3. Kalso EA, Poyhia R, Rosenberg PH, (1991) Spinal antinociception by dexmedetomidine, a highly selective alpha 2-adrenergic agonist. Pharmacol Toxicol 68: 140-143.
4. Hwang YP, Yun HJ, Choi JH, Han EH, Kim HG, et al. (2011) Suppression of EGF-induced tumor cell migration and matrix metalloproteinase-9 expression by capsaicin via the inhibition of EGFR-mediated FAK/Akt, PKC/Raf/ERK, p38 MAPK, and AP-1 signaling. Mol Nutr Food Res 55: 594-605.
5. Lee MJ, Shin TJ, Lee JE, Choo H, Koh HY, et al. (2010) KST5468, a new T-type calcium channel antagonist, has an antinociceptive effect on inflammatory and neuropathic pain models. Pharmacol Biochem Behav 97: 198-204.
6. Sawatzky DA, Willoughby DA, Colville-Nash PR, Rossi AG, (2006) The involvement of the apoptosis-modulating proteins ERK 1/2, Bcl-xL and Bax in the resolution of acute inflammation in vivo. Am J Pathol 168: 33-41.
7. Tashiro A, Okamoto K, Bereiter DA, (2009) Chronic inflammation and estradiol interact through MAPK activation to affect TMJ nociceptive processing by trigeminal caudalis neurons. Neuroscience 164: 1813-1820.
8. Gao YJ, Ji RR, (2009) c-Fos and pERK, which is a better marker for neuronal activation and central sensitization after noxious stimulation and tissue injury? Open Pain J 2: 11-17.
9. Liu H, Zhang HX, Hou HY, Lu XF, Wei JQ, et al. (2011) Acid solution is a suitable medium for introducing QX-314 into nociceptors through TRPV1 channels to produce sensory-specific analgesic effects. PLoS One. United States: 2011 Liu,et al. pp. e29395.
10. Zimmermann M, (1983) Ethical guidelines for investigations of experimental pain in conscious animals. Pain 16: 109-110.
11. Hylden JL, Wilcox GL, (1980) Intrathecal morphine in mice: a new technique. Eur J Pharmacol 67: 313-316.
12. Guan XH, Lu XF, Zhang HX, Wu JR, Yuan Y, et al. (2010) Phosphatidylinositol 3-kinase mediates pain behaviors induced by activation of peripheral ephrinBs/EphBs signaling in mice. Pharmacol Biochem Behav. United States: 2010 Elsevier Inc. 315-324.
13. Ruan JP, Zhang HX, Lu XF, Liu YP, Cao JL, (2010) EphrinBs/EphBs signaling is involved in modulation of spinal nociceptive processing through a mitogen-activated protein kinases-dependent mechanism. Anesthesiology 112: 1234-1249.
14. Leszczynska K, Kau ST, (1992) A sciatic nerve blockade method to differentiate drug-induced local anesthesia from neuromuscular blockade in mice. J Pharmacol Toxicol Methods 27: 85-93.
15. Li LY, Li JL, Zhang HM, Yang WM, Wang K, et al. (2012) TGFbeta1 Treatment Reduces Hippocampal Damage, Spontaneous Recurrent Seizures, and Learning Memory Deficits in Pilocarpine-Treated Rats. J Mol Neurosci.
16. Lee YJ, Park HH, Koh SH, Choi NY, Lee KY, (2011) Amlodipine besylate and amlodipine camsylate prevent cortical neuronal cell death induced by oxidative stress. J Neurochem 119: 1262-1270.
17. Werdehausen R, Fazeli S, Braun S, Hermanns H, Essmann F, et al. (2009) Apoptosis induction by different local anaesthetics in a neuroblastoma cell line. British Journal of Anaesthesia 103: 711-718.
18. Werdehausen R, Braun S, Essmann F, Schulze-Osthoff K, Walczak H, et al. (2007) Lidocaine induces apoptosis via the mitochondrial pathway independently of death receptor signaling. Anesthesiology 107: 136-143.
19. Perez-Castro R, Patel S, Garavito-Aguilar ZV, Rosenberg A, Recio-Pinto E, et al. (2009) Cytotoxicity of local anesthetics in human neuronal cells. Anesth Analg. United States. 997-1007.
20. Drizin I, Gomtsyan A, Bayburt EK, Schmidt RG, Zheng GZ, et al. (2006) Structure-activity studies of a novel series of 5,6-fused heteroaromatic ureas as TRPV1 antagonists. Bioorg Med Chem 14: 4740-4749.
21. Jones NG, Slater R, Cadiou H, McNaughton P, McMahon SB, (2004) Acid-induced pain and its modulation in humans. J Neurosci 24: 10974-10979.
22. Ries CR, Pillai R, Chung CC, Wang JT, MacLeod BA, et al. (2009) QX-314 produces long-lasting local anesthesia modulated by transient receptor potential vanilloid receptors in mice. Anesthesiology 111: 122-126.
23. Mendoza MC, Er EE, Blenis J (2011) The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation. Trends Biochem Sci. England: 2011 Elsevier Ltd. 320-328.
24. Dahmani S, Paris A, Jannier V, Hein L, Rouelle D, et al. (2008) Dexmedetomidine increases hippocampal phosphorylated extracellular signal-regulated protein kinase 1 and 2 content by an alpha 2-adrenoceptor-independent mechanism: evidence for the involvement of imidazoline I1 receptors. Anesthesiology 108: 457-466.
25. Nestler EJ, Carlezon WA Jr, (2006) The mesolimbic dopamine reward circuit in depression. Biol Psychiatry 59: 1151-1159.
26. Hunt SP, Pini A, Evan G, (1987) Induction of c-fos-like protein in spinal cord neurons following sensory stimulation. Nature 328: 632-634.
27. Konakci S, Adanir T, Yilmaz G, Rezanko T, (2008) The efficacy and neurotoxicity of dexmedetomidine administered via the epidural route. Eur J Anaesthesiol 25: 403-409.
28. Sites BD, Taenzer AH, Herrick MD, Gilloon C, Antonakakis J, et al. (2012) Incidence of local anesthetic systemic toxicity and postoperative neurologic symptoms associated with 12,668 ultrasound-guided nerve blocks: an analysis from a prospective clinical registry. Reg Anesth Pain Med 37: 478-482.
29. Bruzzone A, Pinero CP, Castillo LF, Sarappa MG, Rojas P, et al. (2008) Alpha2-adrenoceptor action on cell proliferation and mammary tumour growth in mice. Br J Pharmacol 155: 494-504.
30. Sanders RD, Sun P, Patel S, Li M, Maze M, et al. (2010) Dexmedetomidine provides cortical neuroprotection: impact on anaesthetic-induced neuroapoptosis in the rat developing brain. Acta Anaesthesiol Scand 54: 710-716.