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Characterization of cerebral cortical endocannabinoid levels in a rat inguinal surgery model using liquid chromatography–tandem mass spectrometry (LC–MS/MS)

Published online by Cambridge University Press:  29 July 2019

M. Ita  and
J. Kelly
M. Ita*
Affiliation:
Department of Academic Surgery, Cork University Hospital, Cork, Ireland
J. Kelly
Affiliation:
Department of Pharmacology and Therapeutics, School of Medicine, National University of Ireland, Galway, Ireland
*
*Address for correspondence: Dr M. Ita, Department of Academic Surgery, Cork University Hospital, Ireland. (Email: [email protected])
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Abstract

Background:

The brain endocannabinoid system is believed to play significant roles in anti-nociception, fear response, anxiety, and stress. This study investigated the effects of rat inguinal surgery on the levels of endocannabinoids in the cerebral cortex.

Aim:

The aim of this study was to investigate the effects of acute post-surgical pain on the levels of endocannabinoids in the cerebral cortex.

Methods:

Quantitation of endocannabinoids in the rat cerebral cortex was performed by liquid chromatography–tandem mass spectrometry.

Results:

There was no significant difference in the cerebral cortical levels of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) between the sham and surgery experimental groups. However, there were lateralized differences in the levels of these endocannabinoids between the right and left cerebral cortices irrespective of the two groups. The concentrations of AEA and 2-AG were significantly higher in the right cerebral cortex compared to the contralateral cerebral cortex.

Conclusion:

Acute post-surgical pain did not induce significant alterations in the cerebral cortical levels of endocannabinoids in this study, but the phenomenon of lateralization of the cerebral cortical AEA and 2-AG levels was observed; this latter finding may be related to the role played by endocannabinoids in fear conditioning.

Keywords

Acute post-surgical painendocannabinoidsfearlateralizationliquid chromatography–tandem mass spectrometry (LC–MS/MS)rat inguinal surgery model
Type
Original Research
Information
Irish Journal of Psychological Medicine , Volume 39 , Issue 1 , March 2022 , pp. 54 - 63
Copyright
© The Author(s), 2019. Published by Cambridge University Press on behalf of The College of Psychiatrists of Ireland

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References

Akirav, I (2011). The role of cannabinoids in modulating emotional and non-emotional memory processes in the hippocampus. Frontiers in Behavioral Neuroscience 5, 34.10.3389/fnbeh.2011.00034CrossRefGoogle ScholarPubMed
Alkaitis, MS, Solorzano, C, Landry, RP, Piomelli, D, DeLeo, JA, Romero-Sandoval, EA (2010). Evidence for a role of endocannabinoids, astrocytes and p38 phosphorylation in the resolution of postoperative pain. PLoS One 5(5): e10891.10.1371/journal.pone.0010891CrossRefGoogle ScholarPubMed
Amid, PK, Shulman, AG, Lichtenstein, IL (1996). Open. “tension-free” repair of inguinal hernias: the Lichtenstein technique. European Journal of Surgery 162, 447–453.Google ScholarPubMed
Bari, M, Battista, N, Fezza, F, Gasperi, V, Maccarrone, M (2006). New insights into endocannabinoid degradation and its therapeutic potential. Mini-Reviews in Medicinal Chemistry 6, 109–120.10.2174/138955706776073466CrossRefGoogle ScholarPubMed
Barrett, KE, Barman, SM, Boitano, S, Brooks, H (2012). Ganong’s Review of Medical Physiology, 24th edn., McGraw Hill Professional: New York.Google Scholar
Beltramo, M, Bernardini, N, Bertorelli, R, Campanella, M, Nicolussi, E, Fredduzzi, S, Reggiani, A (2006). CB2 receptor-mediated antihyperalgesia: possible direct involvement of neural mechanisms. European Journal of Neuroscience 23 (6), 1530–1538.10.1111/j.1460-9568.2006.04684.xCrossRefGoogle ScholarPubMed
Beltramo, M, Piomelli, D. (2000). Carrier-mediated transport and enzymatic hydrolysis of the endogenous cannabinoid 2- arachidonylglycerol. Neuroreport 11, 1231–1235.10.1097/00001756-200004270-00018CrossRefGoogle ScholarPubMed
Beltramo, M, Stella, N, Calignano, A, Lin, SY, Makriyannis, A, Piomelli, D (1997). Functional role of high-affinity anandamide transport, as revealed by selective inhibition. Science 277, 1094–1097.10.1126/science.277.5329.1094CrossRefGoogle ScholarPubMed
Bouaboula, M, Poinot-Chazel, C, Bourrié, B, Canat, X, Calandra, B, Rinaldi-Carmona, M, Le Fur, G, Casellas, P (1995). Activation of mitogen-activated protein kinases by stimulation of the central cannabinoid receptor CB1. Biochemical Journal 312, 637–641.10.1042/bj3120637CrossRefGoogle ScholarPubMed
Bradshaw, HB, Walker, JM (2005). The expanding field of cannabimimetic and related lipid mediators. British Journal of Pharmacology 144, 459–465.10.1038/sj.bjp.0706093CrossRefGoogle ScholarPubMed
Butler, RK, Ford, GK, Hogan, M, Roche, M, Doyle, KM, Kelly, JP, Kendall, DA, Chapman, V, Finn, DP (2011). Fear-induced suppression of nociceptive behaviour and activation of Akt signalling in the rat periaqueductal grey: role of fatty acid amide hydrolase. Journal of Psychopharmacology 26, 83–91.10.1177/0269881111413823CrossRefGoogle ScholarPubMed
Cannich, A, Wotjak, CT, Kamprath, K, Hermann, H, Lutz, B, Marsicano, G (2004). CB1 cannabinoid receptors modulate kinase and phosphatase activity during extinction of conditioned fear in mice. Learning & Memory 11 (5), 625–632.10.1101/lm.77904CrossRefGoogle ScholarPubMed
Cravatt, BF, Giang, DK, Mayfield, SP, Boger, DL, Lerner, RA, Gilula, NB (1996). Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides. Nature 384, 83–87.10.1038/384083a0CrossRefGoogle ScholarPubMed
Curzon, P, Rustay, NR, Browman, KE (2009). Cued and contextual fear conditioning for rodents. In Methods of Behavior Analysis in Neuroscience (ed. Buccafusco, J. J.) 2nd edn. CRC Press/Taylor & Francis: Boca Raton (FL). Chapter 2. (https://www.ncbi.nlm.nih.gov/books/NBK5223/)Google ScholarPubMed
Desarnaud, F, Cadas, H, Piomelli, D (1995). Anandamide amidohydrolase activity in rat-brain microsomes – identification and partial characterization. Journal of Biological Chemistry 270, 6030–6035.10.1074/jbc.270.11.6030CrossRefGoogle ScholarPubMed
Deutsch, DG, Chin, SA (1993). Enzymatic-synthesis and degradation of anandamide, a cannabinoid receptor agonist. Biochemical Pharmacology 46, 791–796.10.1016/0006-2952(93)90486-GCrossRefGoogle ScholarPubMed
Devane, WA, Hanus, L, Breuer, A, Pertwee, RG, Stevenson, LA, Griffin, G, Gibson, D, Mandelbaum, A, Etinger, A, Mechoulam, R (1992). Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258 (5090), 1946–1949.10.1126/science.1470919CrossRefGoogle Scholar
Di Benedetto, B, Kallnik, M, Weisenhorn, DMV, Falls, WA, Wurst, W, Holter, SM (2008). Activation of ERK/MAPK in the lateral amygdala of the mouse is required for acquisition of a fear-potentiated startle response. Neuropsychopharmacology 34 (2), 356–366.10.1038/npp.2008.57CrossRefGoogle ScholarPubMed
Dinh, TP, Freund, TF, Piomelli, D (2002). A role for monoglyceride lipase in 2-arachidonoylglycerol inactivation. Chemistry and Physics of Lipids 121, 149–158.10.1016/S0009-3084(02)00150-0CrossRefGoogle ScholarPubMed
Elphick, MR, Egertova, M (2001). The neurobiology and evolution of cannabinoid signalling. Philosophical Transactions of the Royal Society of London Series B-Biological Sciences 356, 381–408.10.1098/rstb.2000.0787CrossRefGoogle ScholarPubMed
Finn, DP, Chapman, V (2004) Cannabinoids as analgesic agents: evidence from in vivo studies. Current Neuropharmacology 2 (1), 75–89.10.2174/1570159043476918CrossRefGoogle Scholar
Ford, GK, Kieran, S, Dolan, K, Harhen, B, Finn, DP (2011). A role for the ventral hippocampal endocannabinoid system in fear-conditioned analgesia and fear responding in the presence of nociceptive tone in rats. PAIN 152, 2495–2504.10.1016/j.pain.2011.07.014CrossRefGoogle ScholarPubMed
Glass, M, Dragunow, M, Faull, RLM (1997). Cannabinoid receptors in the human brain: a detailed anatomical and quantitative autoradiographic study in the fetal, neonatal and adult human brain. Neuroscience 77, 299–318.10.1016/S0306-4522(96)00428-9CrossRefGoogle ScholarPubMed
Guyton, AC, Hall, JE (2010). Guyton and Hall Textbook of Medical Physiology, 12th edn. Elsevier Health Sciences: Philadelphia.Google Scholar
Herkenham, M, Lynn, AB, Johnson, MR, Melvin, LS, De Costa, BR, Rice, KC (1991). Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study. Journal of Neuroscience 11, 563–83.10.1523/JNEUROSCI.11-02-00563.1991CrossRefGoogle ScholarPubMed
Hill, MN, McLaughlin, RJ, Morrish, AC, Viau, V, Floresco, SB, Hillard, CJ, Gorzalka, BB (2009). Suppression of amygdalar endocannabinoid signaling by stress contributes to activation of the hypothalamic-pituitary-adrenal axis. Neuropsychopharmacology Dec, 34 (13), 2733–45.10.1038/npp.2009.114CrossRefGoogle ScholarPubMed
Hohmann, AG, Tsou, K, Walker, JM (1999). Cannabinoid suppression of noxious heat-evoked activity in wide dynamic range neurons in the lumbar dorsal horn of the rat. Journal of Neurophysiology 81, 575–583.10.1152/jn.1999.81.2.575CrossRefGoogle ScholarPubMed
Howlett, AC, Barth, F, Bonner, TI, Cabral, G, Casellas, P, Devane, WA, Felder, CC, Herkenham, M, Mackie, K, Martin, BR, Mechoulam, R, Pertwee, G (2002). International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacological Reviews 54, 161–202.10.1124/pr.54.2.161CrossRefGoogle ScholarPubMed
Howlett, AC, Song, C, Berglund, BA, Wilken, GH, Pigg, JJ (1998). Characterization of CB1 cannabinoid receptors using receptor peptide fragments and site-directed antibodies. Molecular Pharmacology 53, 504–510.10.1124/mol.53.3.504CrossRefGoogle ScholarPubMed
Kreitzer, AC, Regehr, WG (2002). Retrograde signaling by endocannabinoids. Current Opinion in Neurobiology 12, 324–330.10.1016/S0959-4388(02)00328-8CrossRefGoogle ScholarPubMed
Lafenêtre, P, Chaouloff, F, Marsicano, G (2007). The endocannabinoid system in the processing of anxiety and fear and how CB1 receptors may modulate fear extinction. Pharmacol Res Nov, 56 (5), 367–81.10.1016/j.phrs.2007.09.006CrossRefGoogle ScholarPubMed
LeBlanc, KA (2003). Laparoscopic Hernia Surgery: An Operative Guide. Distributed in the U.S.A. by Oxford University Press: London: Arnold; New York, NY.Google Scholar
Lichtman, AH, Cook, SA, Martin, BR (1996). Investigation of brain sites mediating cannabinoid-induced antinociception in rats: evidence supporting periaqueductal gray involvement. Journal of Pharmacology and Experimental Therapeutics 276, 585–593.Google ScholarPubMed
Mailleux, P, Parmentier, M, Vanderhaeghen, JJ (1992). Distribution of cannabinoid receptor messenger RNA in the human brain: an in situ hybridization histochemistry with oligonucleotides. Neuroscience Letters 143, 200–204.10.1016/0304-3940(92)90265-9CrossRefGoogle Scholar
Marsicano, G, Kuner, R (2008). In: Anatomical Distribution of Receptors, Ligands and Enzymes in the Brain and in the Spinal Cord: Circuitries and Neurochemistry in Cannabinoids in the Brain. (ed. Köfalvi, A.), pp. 161–201. Boston, MA: Springer.Google Scholar
Martin, TJ, Buechler, NL, Kahn, W, Crews, JC, Eisenach, JC (2004). Effects of laparotomy on spontaneous exploratory activity and conditioned operant responding in the rat: a model for postoperative pain. Anesthesiology 101 (1), 191–203.10.1097/00000542-200407000-00030CrossRefGoogle Scholar
Martin, WJ, Coffin, PO, Attias, E, Balinsky, M, Tsou, K, Walker, JM (1999). Anatomical basis for cannabinoid-induced antinociception as revealed by intracerebral microinjections. Brain Research 822, 237–242.10.1016/S0006-8993(98)01368-7CrossRefGoogle ScholarPubMed
Martin, WJ, Tsou, K, Walker, JM (1998). Cannabinoid receptor mediated inhibition of the rat tail-flick reflex after microinjection into the rostral ventromedial medulla. Neuroscience Letters 242, 33–36.10.1016/S0304-3940(98)00044-5CrossRefGoogle ScholarPubMed
Matsuda, LA, Lolait, SJ, Brownstein, MJ, Young, AC, Bonner, TI (1990). Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346, 561–564.10.1038/346561a0CrossRefGoogle ScholarPubMed
Mechoulam, R, Parker, LA (2013). The endocannabinoid system and the brain. Annual Review of Psychology 64, 21–47.10.1146/annurev-psych-113011-143739CrossRefGoogle ScholarPubMed
Meng, ID, Manning, BH, Martin, WJ, Fields, HL (1998). An analgesia circuit activated by cannabinoids. Nature 395, 381–383.10.1038/26481CrossRefGoogle ScholarPubMed
Munro, S, Thomas, KL, Abu-Shaar, M (1993). Molecular characterization of a peripheral receptor for cannabinoids. Nature 365, 61–65.10.1038/365061a0CrossRefGoogle ScholarPubMed
Olango, WM (2012). Investigating the role of the endogenous cannabinoid system in emotional modulation of pain: neurochemical and molecular mechanisms. PhD Thesis, NUI Galway.Google Scholar
Olango, WM, Roche, M, Ford, GK, Harhen, B, Finn, DP (2012). The endocannabinoid system in the rat dorsolateral periaqueductal grey mediates fear-conditioned analgesia and controls fear expression in the presence of nocicpetive tone. British Journal of Pharmacology 165, 2549–2560.10.1111/j.1476-5381.2011.01478.xCrossRefGoogle Scholar
Onaivi, ES, Ishiguro, H, Gong, JP, Patel, S, Perchuk, A, Meozzi, PA, Myers, L, Mora, Z, Tagliaferro, P, Gardner, E, Brusco, A, Akinshola, BE, Liu, QR, Hope, B, Iwasaki, S, Arinami, T, Teasenfitz, L, Uhl, GR (2006). Discovery of the presence and functional expression of cannabinoid CB2 receptors in brain. Annals of the New York Academy Sciences 1074, 514–536.10.1196/annals.1369.052CrossRefGoogle ScholarPubMed
Paxinos, G, Watson, C (1997). The Rat Brain in Stereotaxic Co-ordinates. Academic Press: San Diego.Google Scholar
Pertwee, RG (1997). Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacology and Therapeutics 74, 129–180.10.1016/S0163-7258(97)82001-3CrossRefGoogle ScholarPubMed
Puente, N, Elezgarai, I, Lafourcade, M, Reguero, L, Marsicano, G, Georges, F, Manzoni, OJ, Grandes, P (2010). Localization and function of the cannabinoid CB1 receptor in the anterolateral bed nucleus of the stria terminalis. PLoS One Jan 25, 5 (1), e8869.10.1371/journal.pone.0008869CrossRefGoogle ScholarPubMed
Rea, K, Roche, M, Finn, DP (2007). Supraspinal modulation of pain by cannabinoids: the role of GABA and glutamate. British Journal of Pharmacology 152 (5), 633–648.10.1038/sj.bjp.0707440CrossRefGoogle ScholarPubMed
Ruehle, S, Rey, AA, Remmers, F, Lutz, B (2012). The endocannabinoid system in anxiety, fear memory and habituation. Journal of Psychopharmacology Jan 26 (1), 23–39.10.1177/0269881111408958CrossRefGoogle ScholarPubMed
Tsou, K, Brown, S, Sanudo-Pena, MC, Mackie, K, Walker, JM (1998). Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system. Neuroscience 83, 393–411.10.1016/S0306-4522(97)00436-3CrossRefGoogle ScholarPubMed
Van Sickle, MD, Duncan, M, Kingsley, PJ, Mouihate, A, Urbani, P, Mackie, K, Stella, N, Makriyannis, A, Piomelli, D, Davison, JS, Marnett, LJ, Di Marzo, V, Pittman, QJ, Patel, KD, Sharkey, KA (2005). Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science 310 (5746), 329–332.10.1126/science.1115740CrossRefGoogle ScholarPubMed
Walker, JM, Krey, JF, Chu, CJ, Huang, SM (2002). Endocannabinoids and related fatty acid derivatives in pain modulation. Chemistry and Physics of Lipids 121, 159–172.10.1016/S0009-3084(02)00152-4CrossRefGoogle ScholarPubMed
Zhang, J, Hoffert, C, Vu, HK, Groblewski, T, Ahmad, S, O’Donnell, D (2003). Induction of CB2 receptor expression in the rat spinal cord of neuropathic but not inflammatory chronic pain models. European Journal of Neuroscience 17 (12), 2750–2754.10.1046/j.1460-9568.2003.02704.xCrossRefGoogle Scholar
Zogopoulos, P, Vasileiou, I, Patsouris, E, Theocharis, SE (2013). The role of endocannabinoids in pain modulation. Fundamental & Clinical Pharmacology 27, 64–80.10.1111/fcp.12008CrossRefGoogle ScholarPubMed
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