AccScience Publishing / ITPS / Volume 5 / Issue 2 / DOI: 10.36922/itps.361
Cite this article
81
Download
1791
Views
Journal Browser
Volume | Year
Issue
Search
News and Announcements
View All
REVIEW

Agmatine as a Novel Treatment Option for Neuropathies: Experimental Evidences

Mrunali D. Dhokne1 Madhura P. Dixit1 Mayur B. Kale1 Manish M. Aglawe1 Milind J. Umekar1 Brijesh G. Taksande1*
Show Less
1 Division of Neuroscience, Department of Pharmacology, Shrimati Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra, India
INNOSC Theranostics and Pharmacological Sciences 2022, 5(2), 1–10; https://doi.org/10.36922/itps.361
Submitted: 7 February 2023 | Accepted: 31 March 2023 | Published: 27 April 2023
© 2023 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Abstract

N-methyl-D-aspartate receptor (NMDAR) antagonist, a subclass of glutamate receptors or nitric oxide synthase (NOS) inhibitors, prevents neuronal plasticity. However, neural plasticity plays a major role in the pain caused by inflammation and neuropathy, providing clinical opportunities for the use of NOS inhibitors and NMDAR antagonists in the treatment of chronic pain. The neuromodulator agmatine has both NOS inhibitory and NMDAR antagonistic activity, and it controls a range of neurotransmitters and signaling pathways in the brain and spinal cord. The effects of agmatine on pain modulation are described and explored in this article, along with a potential mechanism of action for these effects. We specifically offer evidence to support further clinical and pre-clinical trials looking into agmatine as a novel therapeutic agent for neuropathic pain.

Keywords
Agmatine
Neuropathic pain
Nitric Oxide
N-methyl-D-aspartate
Funding
None.
References
  1. Jensen, T.S.; Finnerup, N.B. Allodynia and Hyperalgesia in Neuropathic Pain: Clinical Manifestations and Mechanisms. Lancet Neurol., 2014, 13(9), 924–35.

 

  1. Costigan, M.; Scholz, J.; Woolf, C.J. Neuropathic Pain: A Maladaptive Response of the Nervous System to Damage. Annu. Rev. Neurosci., 2009, 32, 1–32.

 

  1. Smith, G.; Wiseman, J.; Harrison, S.; Elliott, P.; Birch, P. Pre Treatment with MK-801, a non-Competitive NMDA Antagonist, Prevents Development of Mechanical Hyperalgesia in a Rat Model of Chronic Neuropathy, but not in a Model of Chronic Inflammation. Neurosci. Lett., 1994, 165(1-2), 79–83.

 

  1. Mao, J.; Price, D.D.; Mayer, D.J.; Lu, J.; Hayes, R.L. Intrathecal MK-801 and Local Nerve Anesthesia Synergistically Reduce Nociceptive Behaviors in Rats with Experimental Peripheral Mononeuropathy. Brain Res., 1992, 576(2), 254–62.

 

  1. Moncada, S.; Higgs, A. Mechanisms of Disease: The L-arginine-nitric Oxide Pathway. N. Engl. J. Med., 1993, 329(27), 2002–12.

 

  1. Rodrigo, J.; Springall, D.R.; Uttenthal, O.; Bentura, M.L.; Abadia-Molina, F.; Riveros-Moreno, V.; Martinez-Murillo, R.; Polak, J.M.; Moncada, S. Localization of Nitric Oxide Synthase in the Adult Rat Brain. Philos.Trans. R. Soc. Lond. B Biol. Sci., 1994, 345(1312), 175–221.

 

  1. Önal, A.; Delen, Y.; Ülker, S.; Soykan, N. Agmatine Attenuates Neuropathic Pain in Rats: Possible Mediation of Nitric Oxide and Noradrenergic Activity in the Brainstem and Cerebellum. Life Sci., 2003, 73(4), 413–28.

 

  1. Rahangdale, S.; Fating, R.; Gajbhiye, M.; Kapse, M.; Inamdar, N.; Kotagale, N.; Umekar, M.; Taksande, B. Involvement of Agmatine in Antidepressant-like Effect of HMG-CoA Reductase Inhibitors in Mice. Eur. J. Pharmacol., 2021, 892, 173739.

 

  1. Taksande, B.G.; Kotagale, N.R.; Tripathi, S.J.; Ugale, R.R.; Chopde, C.T. Antidepressant Like Effect of Selective Serotonin Reuptake Inhibitors Involve Modulation of Imidazoline Receptors by Agmatine. Neuropharmacol, 2009, 57(4), 415–24.

 

  1. Courteix, C.; Privat, A.M.; Pélissier, T.; Hernandez, A.; Eschalier, A.; Fialip, J. Agmatine Induces Antihyperalgesic Effects in Diabetic Rats and a Superadditive Interaction with R (–)-3-(2-Carboxypiperazine-4-yl)-Propyl-1-Phosphonic acid, a N-Methyl-D-aspartate-receptor Antagonist. J. Pharmacol. Exp. Ther., 2007, 322(3), 1237–45.

 

  1. Aglawe, M.M.; Taksande, B.G.; Kuldhariya, S.S.; Chopde, C.T.; Umekar, M.J.; Kotagale, N.R. Participation of Central Imidazoline Binding Sites in Antinociceptive Effect of Ethanol and Nicotine in Rats. Fundam. Clin. Pharmacol., 2014, 28(3), 284–93.

 

  1. Kale, M.; Nimje, N.; Aglawe, M.M.; Umekar, M.; Taksande, B.; Kotagale, N. Agmatine Modulates Anxiety and Depression-like Behaviour in Diabetic Insulin-resistant Rats. Brain Res., 2020, 1747, 147045.

 

  1. Otake, K.; Ruggiero, D.A.; Regunathan, S.; Wang, H.; Milner, T.A.; Reis, D.J. Regional Localization of Agmatine in the Rat Brain: An Immunocytochemical Study. Brain Res., 1998, 787(1), 1–14.

 

  1. Dixit, M.; Upadhya, M.; Taksande, B.; Raut, P.; Umekar, M.; Kotagale, N. Neuroprotective Effect of Agmatine in Mouse Spinal Cord Injury Model: Modulation by Imidazoline Receptors. J. Nat. Sci. Biol. Med., 2018, 9(2), 115–20.

 

  1. Taksande, B.G.; Chopde, C.T.; Umekar, M.J.; Kotagale, N.R. Agmatine Attenuates Hyperactivity and Weight Loss Associated with Activity-based Anorexia in Female Rats. Pharmacol. Biochem. Behav., 2015, 132, 136–41.

 

  1. Kotagale, N.R.; Shirbhate, S.H.; Shukla, P.; Ugale, R.R. Agmatine Attenuates Neuropathic Pain in Sciatic Nerve Ligated Rats: Modulation by Hippocampal Sigma Receptors. Eur. J. Pharmacol., 2013, 714(1-3), 424–31.

 

  1. Kotagale, N.; Rahmatkar, S.; Chauragade, S.; Dixit, M.; Umekar, M.; Chopde, C.; Taksande, B. Involvement of Hippocampal Agmatine in β1-42 Amyloid Induced Memory Impairment, Neuroinflammation and BDNF Signaling Disruption in Mice. NeuroToxicology. 2020, 80, 1–11.

 

  1. Castelli, G.; Desai, K.M.; Cantone, R.E. Peripheral Neuropathy: Evaluation and Differential Diagnosis. Am. Fam. Physician, 2020, 102(12), 732–9.

 

  1. Finnerup, N.B.; Kuner, R.; Jensen, T.S. Neuropathic Pain: From Mechanisms to Treatment. Physiol Rev., 2021, 101(1), 259–301.

 

  1. Jensen, T.S.; Hansson, P.T. Classification of Neuropathic Pain Syndromes Based on Symptoms and Signs. Handb. Clin. Neurol., 2006, 81, 517–26.

 

  1. Zilliox, L. Neuropathic Pain. Continuum (Minneap Minn), 2017, 23(2, Selected Topics in Outpatient Neurology), 512–32.

 

  1. Dworkin, R.H.; O’Connor, A.B.; Audette, J.; Baron, R.; Gourlay, G.K.; Haanpää, M.L.; Kent, J.L.; Krane, E.J.; LeBel, A.A.; Levy, R.M. Recommendations for the Pharmacological Management of Neuropathic Pain: An Overview and Literature Update. Mayo Clin. Proc., 2010, 85, S3–14.

 

  1. Kale, M.B.; Bajaj, K.; Umare, M.; Wankhede, N.L.; Taksande, B.G.; Umekar, M.J.; Upaganlawar, A. Exercise and Nutraceuticals: Eminent Approach for Diabetic Neuropathy. Curr. Mol. Pharmacol., 2022, 15(1), 108–28.

 

  1. Baron, R.; Binder, A.; Wasner, G. Neuropathic Pain: Diagnosis, Pathophysiological Mechanisms, and Treatment. Lancet Neurol., 2010, 9(8), 807–19.

 

  1. Jaggi, A.S.; Jain, V.; Singh, N. Animal Models of Neuropathic Pain. Fundam. Clin. Pharmacol., 2011, 25(1), 1–28.

 

  1. Dworkin, R.H.; O’Connor, A.B.; Backonja, M.; Farrar, J.T.; Finnerup, N.B.; Jensen, T.S.; Kalso, E.A.; Loeser, J.D.; Miaskowski, C.; Nurmikko, T.J. Pharmacologic Management of Neuropathic Pain: Evidence-based Recommendations. Pain, 2007, 132(3), 237–51.

 

  1. Sindrup, S.H.; Otto, M.; Finnerup, N.B.; Jensen, T.S. Antidepressants in the Treatment of Neuropathic Pain. Basic Clin. Pharamacol. Toxicol., 2005, 96(6), 399–409.

 

  1. Gammaitoni, A.R.; Davis, M.W. Pharmacokinetics and Tolerability of Lidocaine Patch 5% with Extended Dosing. Ann. Pharmacother., 2002, 36(2), 236–40.

 

  1. Siddall, P.; Cousins, M.; Otte, A.; Griesing, T.; Chambers, R.; Murphy, T. Pregabalin in Central Neuropathic Pain Associated with Spinal Cord Injury: A Placebo-controlled Trial. Neurology, 2006, 67(10), 1792–800.

 

  1. O’Connor, A.B. Neuropathic Pain: Quality-of-life Impact, Costs and Cost Effectiveness of Therapy. Pharmacoeconomics, 2009, 27, 95–112.

 

  1. Cloninger, C.R. A Unified Biosocial Theory of Personality and its Role in the Development of Anxiety States. Psychiatr. Dev., 1986, 3(2), 167–226.

 

  1. Bennett, G.J. Pathophysiology and Animal Models of Cancer-related Painful Peripheral Neuropathy. Oncologist, 2010, 15(S2), 9–12.

 

  1. Zeltser, R.; Beilin, B.Z.; Zaslansky, R.; Seltzer, Z. Comparison of Autotomy Behavior Induced in Rats by Various Clinically-used Neurectomy Methods. Pain, 2000, 89(1), 19–24.

 

  1. Muthuraman, A.; Jaggi, A.S.; Singh, N.; Singh, D. Ameliorative Effects of Amiloride and Pralidoxime in Chronic Constriction Injury and Vincristine Induced Painful Neuropathy in Rats. Eur. J. Pharmacol., 2008, 587(1-3), 104–11.

 

  1. Devor, M.; Wall, P. Type of Sensory Nerve Fibre Sprouting to form a Neuroma. Nature, 1976, 262(5570), 705–8.

 

  1. Riopelle, J.M. The Ethics of Using Animal Models to Study Treatment of Phantom Pain. J. Am. Soc. Anesthesiologists, 1992, 76(6), 1069–9.

 

  1. Bennett, G.J.; Xie, Y.K. A Peripheral Mononeuropathy in Rat that Produces Disorders of Pain Sensation Like those Seen in Man. Pain, 1988, 33(1), 87–107.

 

  1. Wall, P.D.; Devor, M.; Inbal, R.; Scadding, J.W.; Schonfeld, D.; Seltzer, Z.; Tomkiewicz, M.M. Autotomy Following Peripheral Nerve Lesions: Experimental Anesthesia Dolorosa. Pain, 1979, 7(2), 103–13.

 

  1. Li, S.X.; Cui, N.; Zhang, C.L.; Zhao, X.L.; Yu, S.F.; Xie, K.Q. Effect of Subchronic Exposure to Acrylamide Induced on the Expression of bcl-2, Bax and Caspase-3 in the Rat Nervous System. Toxicology, 2006, 217(1), 46–53.

 

  1. Sacerdote, P.; Franchi, S.; Trovato, A.E.; Valsecchi, A.E.; Panerai, A.E.; Colleoni, M. Transient Early Expression of TNF-α in Sciatic Nerve and Dorsal Root Ganglia in a Mouse Model of Painful Peripheral Neuropathy. Neurosci. Lett., 2008, 436(2), 210–3.

 

  1. Seltzer, Z.; Dubner, R.; Shir, Y. A Novel Behavioral Model of Neuropathic Pain Disorders Produced in Rats by Partial Sciatic Nerve Injury. Pain, 1990, 43(2), 205–18.

 

  1. Malmberg, A.B.; Basbaum, A.I. Partial Sciatic Nerve Injury in the Mouse as a Model of Neuropathic Pain: Behavioral and Neuroanatomical Correlates. Pain, 1998, 76(1-2), 215–22.

 

  1. Vahidy, W.H.; Ong, W.Y.; Farooqui, A.A.; Yeo, J.F. Effects of Intracerebroventricular Injections of Free Fatty Acids, Lysophospholipids, or Platelet Activating Factor in a Mouse Model of Orofacial Pain. Brain Res., 2006, 174, 781–5.

 

  1. Carlton, S.M.; Lekan, H.A.; Kim, S.H.; Chung, J.M. Behavioral Manifestations of an Experimental Model for Peripheral Neuropathy Produced by Spinal Nerve Ligation in the Primate. Pain, 1994, 56(2), 155–66.

 

  1. Kim, S.H.; Chung, J.M. An Experimental Model for Peripheral Neuropathy Produced by Segmental Spinal Nerve Ligation in the Rat. Pain, 1992, 50(3), 355–63.

 

  1. Shields, S.D.; Eckert, W.A. 3rd; Basbaum, A.I. Spared Nerve Injury Model of Neuropathic Pain in the Mouse: A Behavioral and Anatomic Analysis. J. Pain, 2003, 4(8), 465–70.

 

  1. Decosterd, I.; Woolf, C.J. Spared Nerve Injury: An Animal Model of Persistent Peripheral Neuropathic Pain. Pain, 2000, 87(2), 149–58.

 

  1. Yang, G.Y.; Lee, M.K.; Bae, Y.C.; Ahn, D.K. Intracisternal Administration of COX Inhibitors Attenuates Mechanical Allodynia Following Compression of the Trigeminal Ganglion in rats. Prog. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2009, 33(4), 589–95.

 

  1. Ahn, D.K.; Lim, E.J.; Kim, B.C.; Yang, G.Y.; Lee, M.K.; Ju, J.S.; Han, S.R.; Bae, Y.C. Compression of the Trigeminal Ganglion Produces Prolonged Nociceptive Behavior in Rats. Eur. J. Pain., 2009, 13(6), 568–75.

 

  1. Courteix, C.; Eschalier, A.; Lavarenne, J. Streptozocin-induced Diabetic Rats: Behavioural Evidence for a Model of Chronic Pain. Pain, 1993, 53(1), 81–8.

 

  1. Grover, V.S.; Sharma, A.; Singh, M. Role of Nitric Oxide in Diabetes-induced Attenuation of Antinociceptive Effect of Morphine in Mice. Eur. J. Pharmacol., 2000, 399(2-3), 161–4.

 

  1. Genovese, T.; Esposito, E.; Mazzon, E.; Di Paola, R.; Muià, C.; Meli, R.; Bramanti, P.; Cuzzocrea, S. Effect of Cyclopentanone Prostaglandin 15-Deoxy-Δ12, 14PGJ2 on Early Functional Recovery from Experimental Spinal Cord Injury. Shock, 2008, 30(2), 142–52.

 

  1. Kumar, A.; Kaur, H.; Singh, A. Neuropathic Pain Models Caused by Damage to Central or Peripheral Nervous System. Pharmacol. Rep., 2018, 70(2), 206–16.

 

  1. Taksande, B.G.; Faldu, D.S.; Dixit, M.P.; Sakaria, J.N.; Aglawe, M.M.; Umekar, M.J.; Kotagale, N.R. Agmatine Attenuates Chronic Unpredictable Mild Stress Induced Behavioral Alteration in Mice. Eur. J. Pharmacol., 2013, 720(1-3), 115–20.

 

  1. Donertas, B.; Erol, K. Cannabinoids and Agmatine as Potential Therapeutic Alternatives for Cisplatin-induced Peripheral Neuropathy. J. Exp Pharmcol., 2018, 10, 19–28.

 

  1. Regunathan, S. Agmatine: Biological Role and Therapeutic Potentials in Morphine Analgesia and Dependence. AAPS J., 2006, 8, E479–84.

 

  1. Yeşilyurt, Ö.; Uzbay, I.T. Agmatine Potentiates the Analgesic Effect of Morphine by an α2-Adrenoceptor-mediated Mechanism in Mice. Neuropsychopharmacology, 2001, 25(1), 98–103.

 

  1. Taksande, B.G.; Sharma, O.; Aglawe, M.M.; Kale, M.B.; Gawande, D.Y.; Umekar, M.J.; Kotagale, N.R. Acute Orexigenic Effect of Agmatine Involves Interaction Between Central α2- Adrenergic and GABAergic Receptors. Biomed. Pharmacother., 2017, 93, 939–47.

 

  1. Chimthanawala, N.; Patil, S.; Agrawal, R.; Kotagale, N.R.; Umekar, M.J.; Taksande, B.G. Inhibitory Influence of Agmatine in Ethanol Withdrawal-induced Depression in Rats: Behavioral and Neurochemical Evidence. Alcohol, 2020, 83, 67–74.

 

  1. Kotagale, N.R.; Taksande, B.G.; Inamdar, N.N. Neuroprotective Offerings by Agmatine. Neurotoxicology, 2019, 73, 228–45.

 

  1. Taksande, B.G.; Gawande, D.Y.; Chopde, C.T.; Umekar, M.J.; Kotagale, N.R. Agmatine Ameliorates Adjuvant Induced Arthritis and Inflammatory Cachexia in Rats. Biomed. Pharmacother., 2017, 86, 271–8.

 

  1. Kolesnikov, Y.; Jain, S.; Pasternak, G.W. Modulation of Opioid Analgesia by Agmatine. Eur. J. Pharmacol., 1996, 296(1), 17–22.

 

  1. Kotagale, N.R.; Mendhi, S.M.; Aglawe, M.M.; Umekar, M.J.; Taksande, B.G. Evidences for the Involvement of Sigma Receptors in Antidepressant Like Effect of Quetiapine in Mice. Eur. J. Pharmacol., 2013, 702(1-3), 180–6.

 

  1. Gawali, V.S.; Marde, S.V.; Kale, B.N.; Dhokne, D.M.; Kale, B.M.; Wankhede, L.N.; Taksande, G.B.; Umekar, J.M.; Upaganlawar, B.A. Mitochondrial Dysfunction in Neurodevelopmental Disorders: A Systematic Review on Pathways and Mechanisms. Curr. Indian Sci., 2023, 1(1), 1-10.

 

  1. Yang, X.C.; Reis, D.J. Agmatine Selectively Blocks then-methyl-d-aspartate Subclass of Glutamate Receptor Channels in Rat Hippocampal Neurons. J. Pharmacol. Exp. Ther., 1999, 288(2), 544–9.

 

  1. Palacios, G.; Muro, A.; Verdú, E.; Pumarola, M.; Vela, J.M. Immunohistochemical Localization of the Sigma1 Receptor in Schwann Cells of Rat Sciatic Nerve. Brain Res., 2004, 1007(1-2), 65–70.

 

  1. De la Puente, B.; Nadal, X.; Portillo-Salido, E.; Sánchez-Arroyos, R.; Ovalle, S.; Palacios, G.; Muro, A.; Romero, L.; Entrena, J.M.; Baeyens, J.M. Sigma-1 Receptors Regulate Activity-induced Spinal Sensitization and Neuropathic Pain After Peripheral Nerve Injury. Pain, 2009, 145(3), 294–303.

 

  1. Martuscello, R.T.; Spengler, R.N.; Bonoiu, A.C.; Davidson, B.A.; Helinski, J.; Ding, H.; Mahajan, S.; Kumar, R.; Bergey, E.J.; Knight, P.R. Increasing TNF Levels Solely in the Rat Hippocampus Produces Persistent Pain-like Symptoms. Pain, 2012, 153(9), 1871–882.

 

  1. Chandurkar, P.; Dhokne, M.; Wankhede, N.; Mangrulkar, S.; Taksande, B.; Upaganlawar, A.; Umekar, M.; Kale, M. Modulation of Mitochondrial Function in Elderly Brain: Involvement of Autophagy and Apoptosis. ITPS, 2023, 4(2), 33–45.

 

  1. Tiwari, P.; Wankhede, N.; Badole, S.; Umare, M.; Taksande, B.; Upaganlawar, A.; Umekar, M.; Kale, M. Mitochondrial Dysfunction in Ageing: Involvement of Oxidative Stress and Role of Melatonin. Bull. Environ. Pharmacol. Life Sci., 2021, 10, 156–72.

 

  1. Marde, V.S.; Tiwari, P.L.; Wankhede, N.L.; Taksande, B.G.; Upaganlawar, A.B.; Umekar, M.J.; Kale, M.B. Neurodegenerative Disorders Associated with Genes of Mitochondria. Fut. J. Pharma. Sci., 2021, 7, 66.

 

  1. Marde, V.S.; Atkare, U.A.; Gawali, S.V.; Tiwari, P.L.; Badole, S.P.; Wankhede, N.L.; Taksande, B.G.; Upaganlawar, A.B.; Umekar, M.J.; Kale, M.B. Alzheimer’s Disease and Sleep Disorders: Insights into the Possible Disease Connections and the Potential Therapeutic Targets. Asian J. Psychiatr., 2022, 68, 102961.

 

  1. Taksande, B.G.; Kotagale, N.R.; Patel, M.R.; Shelkar, G.P.; Ugale, R.R.; Chopde, C.T. Agmatine, an Endogenous Imidazoline Receptor Ligand Modulates Ethanol Anxiolysis and withdrawal Anxiety in Rats. Eur. J. Pharmacol., 2010, 637(1-3), 89–101.

 

  1. Dixit, M.P.; Sammeta, S.S.; Dhokne, M.D.; Mangrulkar, S.; Upadhya, M.A.; Umekar, M.J.; Taksande, B.G.; Kotagale, N.R. Chronic Agmatine Treatment Prevents Olanzapine-induced Obesity and Metabolic Dysregulation in Female Rats. Brain Res. Bull., 2022, 191, 69–77.

 

  1. Moulin, D.; Boulanger, A.; Clark, A.; Clarke, H.; Dao, T.; Finley, G.; Furlan, A.; Gilron, I.; Gordon, A.; Morley-Forster, P.K. Pharmacological Management of Chronic Neuropathic Pain: Revised Consensus Statement from the Canadian Pain Society. Pain Res. Manag., 2014, 19(6), 328–35.

 

  1. Kotagale, N.R.; Taksande, B.G.; Gahane, A.Y.; Ugale, R.R.; Chopde, C.T. Repeated Agmatine Treatment Attenuates Nicotine Sensitization in Mice: Modulation by α2-Adrenoceptors. Behav. Brain Res., 2010, 213(2), 161–74.

 

  1. Fairbanks, C.A.; Schreiber, K.L.; Brewer, K.L.; Yu, C.G.; Stone, L.S.; Kitto, K.F.; Nguyen, H.O.; Grocholski, B.M.; Shoeman, D.W.; Kehl, L.J.; Regunathan, S.; Reis, D.J.; Yezierski, R.P.; Wilcox, G.L. Agmatine Reverses Pain Induced by Inflammation, Neuropathy, and Spinal Cord Injury. Proc. Natl. Acad. Sci. U S A, 2000, 97(19), 10584–9.

 

  1. Aricioğlu, F. Effect of Harmane on Mononeuropathic Pain in Rats. Ann. N. Y Acad. Sci., 2003, 1009, 180–4.

 

  1. Karadag, H.C.; Ulugol, A.; Tamer, M.; Ipci, Y.; Dokmeci, I. Systemic Agmatine Attenuates Tactile Allodynia in Two Experimental Neuropathic Pain Models in Rats. Neurosci. Lett., 2003, 339(1), 88–90.

 

  1. Paszcuk, A.F.; Gadotti, V.M.; Tibola, D.; Quintão, N.L.; Rodrigues, A.L.S.; Calixto, J.B.; Santos, A.R. Anti-hypernociceptive Properties of Agmatine in Persistent Inflammatory and Neuropathic Models of Pain in Mice. Brain Res., 2007, 1159, 124–33.
Conflict of interest
The authors declare no conflicts of interest.
Share
Back to top
INNOSC Theranostics and Pharmacological Sciences, Electronic ISSN: 2705-0823 Published by AccScience Publishing