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http://dx.doi.org/10.3344/kjp.2015.28.2.96

Anti-allodynic Efficacy of NMDA Antagonist Peptide and Noradrenaline Alone and in Combination in Rodent Neuropathic Pain Model  

Nasirinezhad, Farinaz (Physiology Research Center, Department of Physiology, Iran University of Medical Sciences)
Hosseini, Marjan (Physiology Research Center, Department of Physiology, Iran University of Medical Sciences)
Salari, Sajad (Department of Physiology, Ilam University of Medical Sciences)
Publication Information
The Korean Journal of Pain / v.28, no.2, 2015 , pp. 96-104 More about this Journal
Abstract
Background: The present experiment was conducted to identify the cooperative effect of serine histogranin (SHG) and noradrenaline in alleviating peripheral neuropathic pain. Methods: Chronic constriction injury of the right sciatic nerve was used to induce chronic neuropathic pain. For drug delivery, a PE10 tube was inserted into the subarachnoid space. Acetone drops and a $44^{\circ}C$ water bath were used to evaluate the cold and heat allodynia, respectively. Placing and grasping reflexes were used to assess the locomotor system. Results: SHG at 0.5 and $1{\mu}g$significantly (P < 0.05) decreased the thermal allodynia. The cold allodynia was also significantly reduced by intrathecal injections of 0.5 (P < 0.05) and $1{\mu}g$(P < 0.001) of SHG. $1{\mu}g$of noradrenaline, but not $0.5{\mu}g$, significantly alleviated the cold (P < 0.01) and thermal (P < 0.05) allodynia. The ameliorating effect of noradrenaline or SHG disappeared when the two compounds were administrated in equal concentrations. A significant difference (P < 0.01 in the acetone and P < 0.05 in the heat) was observed in the groups under equal doses of the two compounds, with a lower effectiveness of the combination therapy. Conclusions: Our findings suggest that the simultaneous administrations of noradrenaline and SHG do not result in synergistic analgesia, and combination therapy may not be a good approach to the treatment of chronic neuropathic pain syndrome.
Keywords
Antagonists and Inhibitors; Neuropathic pain; Noradrenaline; N-Methyl-D-Aspartate; Receptors;
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1 D'Angelo R, Morreale A, Donadio V, Boriani S, Maraldi N, Plazzi G, et al. Neuropathic pain following spinal cord injury: what we know about mechanisms, assessment and management. Eur Rev Med Pharmacol Sci 2013; 17: 3257-61.
2 Hosseini M, Karami Z, Janzadenh A, Jameie SB, Haji Mashadi Z, Yousefifard M, et al. The effect of intrathecal administration of muscimol on modulation of neuropathic pain symptoms resulting from spinal cord injury; an experimental study. Emergency 2014; 2: 151-7.
3 Okazaki R, Namba H, Yoshida H, Okai H, Taguchi K, Kawamura M. Combined antiallodynic effect of $Neurotropin^{(R)}$ and pregabalin in rats with L5-spinal nerve ligation. Life Sci 2013; 92: 259-65.   DOI
4 NasiriNezhad F, Sagen J. NMDA antagonist peptide supplementation enhances pain alleviation by adrenal medullary transplants. Cell Transplant 2005; 14: 203-11.   DOI
5 Nasiri Nejad F, Manaheji H. Sensory and motor behaviors of neuropathic rats following spinal transplantation of chromaffin cells. Razi J Med Sci 2003; 9: 581-92.
6 Siegan JB, Hama AT, Sagen J. Suppression of neuropathic pain by a naturally-derived peptide with NMDA antagonist activity. Brain Res 1997; 755: 331-4.   DOI
7 Hahm TS, Ahn HJ, Ryu S, Gwak MS, Choi SJ, Kim JK, et al. Combined carbamazepine and pregabalin therapy in a rat model of neuropathic pain. Br J Anaesth 2012; 109: 968-74.   DOI
8 Amin B, Hajhashemi V, Hosseinzadeh H, Abnous K. Antinociceptive evaluation of ceftriaxone and minocycline alone and in combination in a neuropathic pain model in rat. Neuroscience 2012; 224: 15-25.   DOI
9 Hama A, Basler A, Sagen J. Enhancement of morphine antinociception with the peptide N-methyl-D-aspartate receptor antagonist [Ser1]-histogranin in the rat formalin test. Brain Res 2006; 1095: 59-64.   DOI
10 Rojo ML, Rodriguez-Gaztelumendi A, Pazos A, Diaz A. Differential adaptive changes on serotonin and noradrenaline transporters in a rat model of peripheral neuropathic pain. Neurosci Lett 2012; 515: 181-6.   DOI
11 Jiang LY, Li SR, Zhao FY, Spanswick D, Lin MT. Norepinephrine can act via alpha(2)-adrenoceptors to reduce the hyper-excitability of spinal dorsal horn neurons following chronic nerve injury. J Formos Med Assoc 2010; 109: 438-45.   DOI
12 Tallarida RJ. Revisiting the isobole and related quantitative methods for assessing drug synergism. J Pharmacol Exp Ther 2012; 342: 2-8.   DOI
13 Nama S, Meenan DR, Fritz WT. The use of sub-anesthetic intravenous ketamine and adjuvant dexmedetomidine when treating acute pain from CRPS. Pain Physician 2010; 13: 365-8.
14 Romero TR, Guzzo LS, Perez AC, Klein A, Duarte ID. Noradrenaline activates the NO/cGMP/ATP-sensitive K(+) channels pathway to induce peripheral antinociception in rats. Nitric Oxide 2012; 26: 157-61.   DOI
15 Luccini E, Musante V, Neri E, Brambilla Bas M, Severi P, Raiteri M, et al. Functional interactions between presynaptic NMDA receptors and metabotropic glutamate receptors co-expressed on rat and human noradrenergic terminals. Br J Pharmacol 2007; 151: 1087-94.
16 Crosby G, Russo MA, Szabo MD, Davies KR. Subarachnoid clonidine reduces spinal cord blood flow and glucose utilization in conscious rats. Anesthesiology 1990; 73: 1179-85.   DOI
17 Raiteri M. Functional pharmacology in human brain. Pharmacol Rev 2006; 58: 162-93.   DOI
18 Alagarsamy S, Saugstad J, Warren L, Mansuy IM, Gereau RW 4th, Conn PJ. NMDA-induced potentiation of mGluR5 is mediated by activation of protein phosphatase 2B/calcineurin. Neuropharmacology 2005; 49 Suppl 1: 135-45.
19 Pittaluga A, Pattarini R, Severi P, Raiteri M. Human brain N-methyl-D-aspartate receptors regulating noradrenaline release are positively modulated by HIV-1 coat protein gp120. AIDS 1996; 10: 463-8.   DOI
20 Kamisaki Y, Hamada T, Maeda K, Ishimura M, Itoh T. Presynaptic alpha 2 adrenoceptors inhibit glutamate release from rat spinal cord synaptosomes. J Neurochem 1993; 60: 522-6.   DOI
21 Nishiyama T, Gyermek L, Lee C, Kawasaki-Yatsugi S, Yamaguchi T, Hanaoka K. The analgesic interaction between intrathecal clonidine and glutamate receptor antagonists on thermal and formalin-induced pain in rats. Anesth Analg 2001; 92: 725-32.   DOI
22 Joo G, Horvath G, Klimscha W, Kekesi G, Dobos I, Szikszay M, et al. The effects of ketamine and its enantiomers on the morphine- or dexmedetomidine-induced antinociception after intrathecal administration in rats. Anesthesiology 2000; 93: 231-41.   DOI
23 Parodi M, Patti L, Grilli M, Raiteri M, Marchi M. Nicotine has a permissive role on the activation of metabotropic glutamate 5 receptors coexisting with nicotinic receptors on rat hippocampal noradrenergic nerve terminals. Neurochem Int 2006; 48: 138-43.   DOI
24 Horvath G, Joo G, Dobos I, Klimscha W, Toth G, Benedek G. The synergistic antinociceptive interactions of endomorphin- 1 with dexmedetomidine and/or S(+)-ketamine in rats. Anesth Analg 2001; 93: 1018-24.   DOI
25 Siegan JB, Sagen J. Attenuation of NMDA-induced spinal hypersensitivity by adrenal medullary transplants. Brain Res 1995; 680: 88-98.   DOI
26 Mladenova G, Annedi SC, Ramnauth J, Maddaford SP, Rakhit S, Andrews JS, et al. First-in-class, dual-action, 3,5- disubstituted indole derivatives having human nitric oxide synthase (nNOS) and norepinephrine reuptake inhibitory (NERI) activity for the treatment of neuropathic pain. J Med Chem 2012; 55: 3488-501.   DOI
27 Tallarida RJ. Quantitative methods for assessing drug synergism. Genes Cancer 2011; 2: 1003-8.   DOI