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Journal of Anesthesia

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01-12-2014 | Original Article

The mu opioid receptor activation does not affect ischemia-induced agonal currents in rat spinal ventral horn

Authors: Hiroyuki Honda, Hiroshi Baba, Tatsuro Kohno

Published in: Journal of Anesthesia | Issue 6/2014

Abstract

Purpose

Opioid-induced spastic paraplegia after transient spinal cord ischemia during aortic surgery has been reported. Opioids modulate neurotransmission through mu (μ) opioid receptors (MORs) in the spinal ventral horn. However, their effects during ischemic insult are not understood.

Methods

The effects of the selective μ agonist [d-Ala²,-N-Me-Phe⁴, Gly⁵-ol]enkephalin (DAMGO) on ischemia-induced agonal currents were examined in the spinal lamina IX neurons of neonatal rats by using the whole-cell patch-clamp technique. Ischemia was simulated in vitro by oxygen/glucose deprivation.

Results

DAMGO (1 μM) produced outward currents in ~60 % of spinal lamina IX neurons at a holding potential of −70 mV. Superfusion with ischemia-simulating medium elicited an agonal current. The latency was 457 ± 18 s. Despite its neuromodulatory effects, DAMGO did not significantly change the latencies of the agonal currents with (440 ± 23 s) or without (454 ± 33 s) DAMGO-induced currents.

Conclusion

Activation of MORs does not influence ongoing ischemia-induced neuronal death. Our findings indicate that MOR agonist administration should be suitable as an anesthetic during aortic surgery.

Svensson LG, Patel V, Robinson MF, Ueda T, Roehm JO Jr, Crawford ES. Influence of preservation or perfusion of intraoperatively identified spinal cord blood supply on spinal motor evoked potentials and paraplegia after aortic surgery. J Vasc Surg. 1991;13:355–65.PubMedCrossRef

Svensson LG, Crawford ES, Hess KR, Coselli JS, Safi HJ. Experience with 1509 patients undergoing thoracoabdominal aortic operations. J Vasc Surg. 1993;17:357–70.PubMedCrossRef

Rothman SM. Synaptic activity mediates death of hypoxic neurons. Science. 1983;220:536–7.PubMedCrossRef

Lipton SA, Rosenberg PA. Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med. 1994;330:613–22.PubMedCrossRef

Hara MR, Snyder SH. Cell signaling and neuronal death. Annu Rev Pharmacol Toxicol. 2007;47:117–41.PubMedCrossRef

de Haan P, Kalkman CJ, Jacobs MJ. Pharmacologic neuroprotection in experimental spinal cord ischemia: a systematic review. J Neurosurg Anesthesiol. 2001;13:3–12.PubMedCrossRef

North RA. Cellular actions of opiates and cocaine. Ann N Y Acad Sci. 1992;28(654):1–6.CrossRef

Williams JT, Christie MJ, Manzoni O. Cellular and synaptic adaptations mediating opioid dependence. Physiol Rev. 2001;81:299–343.PubMed

Ikoma M, Kohno T, Baba H. Differential presynaptic effects of opioid agonists on A-delta- and C-afferent glutamatergic transmission to the spinal dorsal horn. Anesthesiology. 2007;107:807–12.PubMedCrossRef

10.

Kohno T, Kumamoto E, Higashi H, Shimoji K, Yoshimura M. Actions of opioids on excitatory and inhibitory transmission in substantia gelatinosa of adult rat spinal cord. J Physiol. 1999;518:803–13.PubMedCentralPubMedCrossRef

11.

Yoshimura M, North RA. Substantia gelatinosa neurones hyperpolarized in vitro by enkephalin. Nature (Lond). 1983;305:529–30.CrossRef

12.

Mansour A, Fox CA, Akil H, Watson SJ. Opioid-receptor mRNA expression in the rat CNS: anatomical and functional implications. Trends Neurosci. 1995;18:22–9.PubMedCrossRef

13.

Gouarderes C, Beaudet A, Zajac JM, Cros J, Quirion R. High resolution radioautographic localization of [¹²⁵I]FK-33-824-labelled mu opioid receptors in the spinal cord of normal and deafferented rats. Neuroscience. 1991;43:197–209.PubMedCrossRef

14.

Kar S, Quirion R. Neuropeptide receptors in developing and adult rat spinal cord: an in vitro quantitative autoradiography study of calcitonin gene-related peptide, neurokinins, mu-opioid, galanin, somatostatin, neurotensin and vasoactive intestinal polypeptide receptors. J Comp Neurol. 1995;354:253–81.PubMedCrossRef

15.

Honda H, Kawasaki Y, Baba H, Kohno T. The mu opioid receptor modulates neurotransmission in the rat spinal ventral horn. Anesth Analg. 2012;115:703–12.PubMed

16.

Kakinohana M, Marsala M, Carter C, Davison JK, Yaksh TL. Neuraxial morphine may trigger transient motor dysfunction after a noninjurious interval of spinal cord ischemia: a clinical and experimental study. Anesthesiology. 2003;98:862–70.PubMedCrossRef

17.

Kakinohana M, Nakamura S, Fuchigami T, Davison KJ, Marsala M, Sugahara K. Mu and delta, but not kappa, opioid agonists induce spastic paraparesis after a short period of spinal cord ischaemia in rats. Br J Anaesth. 2006;96:88–94.PubMedCrossRef

18.

Faden AI, Jacobs TP, Smith MT, Zivin JA. Naloxone in experimental spinal cord ischemia: dose-response studies. Eur J Pharmacol. 1984;103:115–20.PubMedCrossRef

19.

Shirasawa Y, Matsumoto M, Yoshimura M, Yamashita A, Fukuda S, Ishida K, et al. Does high-dose opioid anesthesia exacerbate ischemic spinal cord injury in rabbits? J Anesth. 2009;23:242–8.PubMedCrossRef

20.

Miyazaki N, Nakatsuka T, Takeda D, Nohda K, Inoue K, Yoshida M. Adenosine modulates excitatory synaptic transmission and suppresses neuronal death induced by ischaemia in rat spinal motoneurones. Pflugers Arch. 2008;457:441–51.PubMedCrossRef

21.

Nishi H, Nakatsuka T, Takeda D, Miyazaki N, Sakanaka J, Yamada H, et al. Hypothermia suppresses excitatory synaptic transmission and neuronal death induced by experimental ischemia in spinal ventral horn neurons. Spine. 2007;32:E741–7.PubMedCrossRef

22.

Nohda K, Nakatsuka T, Takeda D, Miyazaki N, Nishi H, Sonobe H, et al. Selective vulnerability to ischemia in the rat spinal cord: a comparison between ventral and dorsal horn neurons. Spine. 2007;32:1060–6.PubMedCrossRef

23.

Wang MY, Kendig JJ. Patch clamp studies of motor neurons in spinal cord slices: a tool for high-resolution analysis of drug actions. Acta Pharmacol Sin. 2000;21:507–15.PubMed

24.

Cheng G, Kendig JJ. Enflurane decreases glutamate neurotransmission to spinal cord motor neurons by both pre- and postsynaptic actions. Anesth Analg. 2003;96:1354–9.PubMedCrossRef

25.

Honda H, Baba H, Kohno T. Electrophysiological analysis of vulnerability to experimental ischemia in neonatal rat spinal ventral horn neurons. Neurosci Lett. 2011;494:161–4.PubMedCrossRef

26.

Tanaka E, Yamamoto S, Kudo Y, Mihara S, Higashi H. Mechanisms underlying the rapid depolarization produced by deprivation of oxygen and glucose in rat hippocampal CA1 neurons in vitro. J Neurophysiol. 1997;78:891–902.PubMed

27.

Thompson RJ, Zhou N, MacVicar BA. Ischemia opens neuronal gap junction hemichannels. Science. 2006;312:924–7.PubMedCrossRef

28.

Ouanonou A, Zhang Y, Zhang L. Changes in the calcium dependence of glutamate transmission in the hippocampal CA1 region after brief hypoxia-hypoglycemia. J Neurophysiol. 1999;82:1147–55.PubMed

29.

Choi DW. Calcium-mediated neurotoxicity: relationship to specific channel types and role in ischemic damage. Trends Neurosci. 1988;11:465–9.PubMedCrossRef

30.

Chao D, Xia Y. Ionic storm in hypoxic/ischemic stress: can opioid receptors subside it? Prog Neurobiol. 2010;90:439–70.PubMedCentralPubMedCrossRef

31.

Rothman S. Synaptic release of excitatory amino acid neurotransmitter mediates anoxic neuronal death. J Neurosci. 1984;4:1884–91.PubMed

32.

Cervetto C, Taccola G. GABA_A and strychnine-sensitive glycine receptors modulate N-methyl-d-aspartate-evoked acetylcholine release from rat spinal motoneurons: a possible role in neuroprotection. Neuroscience. 2008;154:1517–24.PubMedCrossRef

33.

Lapchak PA, Chapman DF, Nunez SY, Zivin JA. Dehydroepiandrosterone sulfate is neuroprotective in a reversible spinal cord ischemia model: possible involvement of GABA (A) receptors. Stroke. 2000;31:1953–6.PubMedCrossRef

34.

Madden KP. Effect of gamma-aminobutyric acid modulation on neuronal ischemia in rabbits. Stroke. 1994;25:2271–4.PubMedCrossRef

35.

Chen M, Tao YX, Gu JG. Inward currents induced by ischemia in rat spinal cord dorsal horn neurons. Mol Pain. 2007;3:10.PubMedCentralPubMedCrossRef

36.

Kiedrowski L. N-Methyl-d-aspartate excitotoxicity: relationships among plasma membrane potential, Na(+)/Ca(2+) exchange, mitochondrial Ca(2+) overload, and cytoplasmic concentrations of Ca(2+), H(+), and K(+). Mol Pharmacol. 1999;56:619–32.PubMed

37.

Verkhratsky A. Physiology and pathophysiology of the calcium store in the endoplasmic reticulum of neurons. Physiol Rev. 2005;85:201–79.PubMedCrossRef

38.

Zhang Y, Lipton P. Cytosolic Ca²⁺ changes during in vitro ischemia in rat hippocampal slices: major roles for glutamate and Na⁺-dependent Ca²⁺ release from mitochondria. J Neurosci. 1999;19:3307–15.PubMed

39.

Formisano L, Noh KM, Miyawaki T, Mashiko T, Bennett MV, Zukin RS. Ischemic insults promote epigenetic reprogramming of mu opioid receptor expression in hippocampal neurons. Proc Natl Acad Sci USA. 2007;104:4170–5.PubMedCentralPubMedCrossRef

40.

Oda Y, Muroishi Y, Misawa H, Suzuki S. Comparative study of gene expression of cholinergic system-related molecules in the human spinal cord and term placenta. Neuroscience. 2004;128:39–49.PubMedCrossRef

Title: The mu opioid receptor activation does not affect ischemia-induced agonal currents in rat spinal ventral horn
Authors: Hiroyuki Honda
Hiroshi Baba
Tatsuro Kohno
Publication date: 01-12-2014
Publisher: Springer Japan
Published in: Journal of Anesthesia / Issue 6/2014
Print ISSN: 0913-8668
Electronic ISSN: 1438-8359
DOI: https://doi.org/10.1007/s00540-014-1829-3

At a glance: The STEP trials

Springer Medicine

The mu opioid receptor activation does not affect ischemia-induced agonal currents in rat spinal ventral horn

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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