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Study for the Antinociceptive Effect and Toxicity of Chronic Intrathecal Infusion of Cannabinoids in Rats  

Yoon, Myung Ha (Department of Anesthesiology and Pain Medicine, Medical School, Chonnam National University)
Bae, Hong Buem (Department of Anesthesiology and Pain Medicine, Medical School, Chonnam National University)
Choi, Jeong II (Department of Anesthesiology and Pain Medicine, Medical School, Chonnam National University)
Bae, Chun Sang (Departments of Anatomy, Medical School, Chonnam National University)
Kim, Seok Jae (Department of Anesthesiology and Pain Medicine, Medical School, Chonnam National University)
Kim, Chang Mo (Department of Anesthesiology and Pain Medicine, Medical School, Chonnam National University)
Jeong, Sung Tae (Department of Anesthesiology and Pain Medicine, Medical School, Chonnam National University)
Kim, Kwang Su (Department of Anesthesiology and Pain Medicine, Medical School, Chonnam National University)
Jin, Won Jong (Department of Anesthesiology and Pain Medicine, Medical School, Chonnam National University)
Kim, Jong Pil (Department of Anesthesiology and Pain Medicine, Medical School, Chonnam National University)
Kim, Jong Sik (Department of Anesthesiology and Pain Medicine, Medical School, Chonnam National University)
Publication Information
The Korean Journal of Pain / v.18, no.2, 2005 , pp. 133-137 More about this Journal
Abstract
Background: Cannabinoids have shown antinociceptive action. The aims of this study were to examine the effect of chronic infusion of a cannabinoids receptors agonist (WIN 55,212-2) for thermal nociception at the spinal level, and to also observe the development of toxicity. Methods: Male Sprague-Dawley rats were implanted with lumbar intrathecal catheters with the nociceptive response (withdrawal response latency) determined by exposing the plantar surface of the hindpaw to radiant heat. Initially, the effect of intrathecal WIN 55,212-2 was evaluated followed by the change in the effect at 1, 2, 3 and 4 weeks after repeated infusion. Finally, the histopathological findings were assessed 1 and 4 weeks following the infusion of WIN 55,212-2. Results: Intrathecal WIN 55,212-2 was found to produce a limited antinociception during the thermal test. %MPE of WIN 55,212-2 at 1, 2, 3, and 4 weeks after infusion was not different from each other. No abnormal pathological findings were observed following a chronic intrathecal infusion of WIN 55,212-2. Conclusions: WIN 55,212-2, a cannabinoids receptors agonist, may be useful in the management of thermal nociception, without changing the effectiveness or causing the toxicity following a chronic infusion at the spinal level.
Keywords
cannabinoids; chronic; intrathecal; rat; thermal test; toxicity;
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1 Pertwee RG: Cannabinoid teceptots and pain. Prog Neurobiol 2001; 63: 569-611.
2 Martin WJ, Loo eM, Basbaum AI: Spinal cannabinoids are anti-allodynic in rats with persistent inflammation. Pain 1999; 82: 199205.
3 Johanek LM, Heitmiller DR, Turner M, Nader N, Hodges J, Simone DA: Cannabinoids attenuate capsaicin-evoked hyperalgesia through spinal and peripheral mechanisms. Pain 2001; 93: 303-15.
4 Giihring H, Schuster J, Hamza M, Ates M, Kotalla CE, Brune K: HU-21O shows higher efficacy and potency than morphine after intrathecal administration in the mouse formalin test. Eur J Pharmacol 2001; 429: 127-34.
5 Yoon MH, Yaksh TL: The effeee of intrathecal gabapentin on pain behavior and hemodynamics on the formalin test in the rat. Anesth Analg 1999; 89: 4.)4-9.
6 Pan X, Ikeda SR, Lewis DL: Rat brain cannabinoid receptor modulates N-type Ca'- channels in a neuronal expression system. Mol Pharmacol 1996; 49 707-14.
7 Howlett AC, Fleming RM: Cannabinoid inhibition of adenylate cyclase. Pharmacology of the response in neuroblastoma cell membranes. Mol Pharmacol 1984; 26: 532-8.
8 Hohmann AG, Martin WJ, Tsou K, Walker JM: Inhibition of noxious stimulus-evoked activity of spinal cord dorsal horn neurons by the cannabinoid WIN 55,212-2. Life Sci 1995; 56: 2111-8.
9 Hanus L, Breuer A, Tchilibon S, Shiloah S, Goldenberg D, Horowitz M, et al: HU-308: a specific agonist for CB(2), a peripheral cannabinoid receptor. Proc Nat! Acad Sci USA 1999; 96: 14228-33.
10 Lichtman AH, Martin BR: The selective cannabinoid antagonist SR 141716A blocks cannabinoid-induced antinociception in rats. Phatmacol Biochem Behav 1997; 57: 7-12.
11 Richatdson JD, Aanonsen L, Hargteaves KM: Antihyperalgesic effects of spinal cannabinoids. Eur J Pharmacol 1998; 345: 145-53.
12 Mason DJ Jr, Lowe J, Welch SP: Cannabinoid modulation of dynorphin A: correlation ro cannabinoid-induced antinociception. Eur J Pharmacol 1999; 378: 237-48.
13 Yoon MH, Choi J1: Pharmacologic interaction between cannabinoid and either clonidine or neostigmine in the rat formalin test. Anesthesiology 2003; 99: 701-7.
14 Mackie K, Hille B: Cannabinoids inhibit Nvtype calcium channels in neuroblastoma-glioma cells. Proc Nat! Acad Sci USA 1992; 89: 3825-9.
15 Twitchell W, Brown S, Mackie K: Cannabinoids inhibit N- and P/Q-type calcium channels in cultured rat hippocampal neurons. J Neurophysiol 1997; 78: 43-50.
16 Rice AS: Cannabinoids and pain. Curt Opin Investig Drugs 2001; 2: 399-414.
17 Burstein SH, Friderichs E, Kogel B, Schneider J, Selve N: Analgesic effects of 1',1' dimethylheptyl-delta8-THC-ll-oic acid (CT3) in mice. Life Sci 1998; 63: 161-8.
18 Walker JM, Huang SM: Cannabinoid analgesia. Pharmacol Ther 2002; 95: 127-35.
19 Deadwyler SA, Hampson RE, Bennett BA, Edwards TA, Mu J, Pacheco MA, et al: Cannabinoids modulate potassium current in cultured hippocampal neurons. Receptors Channels 1993; 1: 121-34.
20 Carta G, Gessa GL, Nava F: Dopamine D(2) receptor antagonists prevent delta(9)-tetrahydrocannabinol-induced antinociception in rats. Eur J Pharmacol 1999; 384: 153-6.
21 Burstein SH, Audette CA, Breuer A, Devane WA, Colodner S, Doyle SA, et al: Synthetic nonpsychotropic cannabinoids with potent antiinflammatory, analgesic, and leukocyte antiadhesion acrivities. J Med Chem 1992; 35: 3135-41.
22 Yaksh TL, Rudy TA: Chronic catheterization of the spinal subarachnoid space. Physiol Behav 1976; 17: 1031-6.
23 Drew LJ, Harris J, Millns PJ, Kendall DA, Chapman V: Activation of spinal cannabinoid 1 receptors inhibits C-fibte driven hyperexcitable neuronal responses and increases [35S}GTPgammaS binding in the dorsal horn of the spinal cord of noninflamed and inflamed rats. Eur J Neurosci 2000; 12: 2079-86.
24 Schatz AR, Lee M, Condie RE, Pulaski JT, Kaminski NE: Cannabinoid receptors CB1 and CB2: a charaeeerization of expression and adenylate cyclase modulation within the immune system. Toxicol Appl Pharmacol 1997; 142: 278-87.
25 Novelli GP, Peduto VA, Betrol E, Mati F, Pieraccioli E: Analgesic interaction between nitrous oxide and delta-9-tetrahydtocannabinol in the tat. Bt J Anaesth 1983; 55: 997-1000.
26 Farquhar-Srnirh WP, Egertova M, Bradbury EJ, McMahon SB, Rice AS, Elphick MR: Cannabinoid CB(l) receptor expression in rat spinal cord. Mol Cell Neurosci 2000; 15: 510-21.
27 Lichtman AH, Martin BR: Cannabinoid-induced antinociception is mediated by a spinal alpha 2-noradrenergic mechanism. Brain Res 1991; 559: 309-14.
28 Hohmann AG, Briley EM, Herkenham M: Pre- and postsynaptic disttibution of cannabinoid and mu opioid receptors in rat spinal cord. Brain Res 1999; 822 17-25.