Veterinary Research Forum
Vet Res Forum

Effects of intracerebroventricular injection of vitamin B12 on formalin-induced muscle pain in rats: Role of cyclooxygenase pathway and opioid receptors

Document Type : Original Article

Authors

Esmaeal Tamaddonfard 1
Sina Tamaddonfard 2
Siamak Cheraghiyan 3

1 Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

2 DVM Student, Faculty of Veterinary Medicine, Urmia Branch of Islamic Azad University, Urmia, Iran

3 Faculty of Veterinary Medicine, Urmia Branch of Islamic Azad University, Urmia, Iran

https://doi.org/10.30466/vrf.2018.33104
Abstract
Vitamin B12 modulates pain at the local and peripheral levels. This study has investigated the effects of intracerebroventricular (ICV) injection of vitamin B12 on themuscle pain. We used diclofenac (cyclooxygenase inhibitor) and naloxone (opioid receptors antagonist) to clarify the possible mechanisms. For ICV injections, a guide cannula was implanted in the left lateral ventricle of the brain. Muscle pain was induced by intramuscular injection of formalin (2.50%; 50 µl) in the right gastrocnemius muscle and the number of paw flinching was recorded at 5-min blocks for 60 min. Locomotor activity was performed using an open-field test. Formalin induced a biphasic pain. Vitamin B12 (1.25, 2.50, 5.00 and 10.00 µg per rat) and diclofenac (12.50 and 25.00 µg per rat) significantly reduced both phases pain intensity. Significant antinociceptive effects were observed after combined treatments of diclofenac (6.25 and 12.50 µg per rat) with vitamin B12 (0.63 and 2.50 µg per rat), respectively. Prior ICV injection of naloxone (10.00 µg per rat) prevented vitamin B12 (10.00 µg per rat) and diclofenac (25.00 µg per rat) induced antinociceptive effects. All the above-mentioned chemicals did not alter locomotor behavior in an open-field test. The present results showed that the cyclooxygenase pathway and opioid receptors may be involved in the central antinociceptive effect of vitamin B12. In addition, opioid receptors might be involved in diclofenac-induced antinociception.

Keywords

Diclofenac
Formalin-induced muscle pain
Opioid receptors
Rats
Vitamin B12
Subjects

  1.  

    1. Mense S. Muscle pain: Mechanisms and clinical significance. Dtsch Arztebl Int 2008; 105(12): 214-219.
    2. Kehl U, Fairbanks CA. Experimental animal models of muscle pain analgesia. Excer Sport Sci Rev 2003; 31(4): 188-194.
    3. Lei J, You HJ. Endogenous descending facilitation and inhibition differ in control of intramuscularly induced persistent muscle nociception. Exp Neurol 2013; 248: 100-111.
    4. Graven-Nielsen T, Arendt-Nielsen L. Assessment of mechanisms in localized and widespread musculoskeletal pain. Nat Rev Rheumatol 2010; 6(10): 599-606.
    5. Said HM. Water-soluble vitamins. In: Bier DM, Mann J, Alpers DH, et al (Eds). Nutrition for the primary care provider. Basel, Switzerland: Karger 2015; 30-37.
    6. Rathod R, Kale A, Joshi S. Novel insights into the effect of vitamin B12 and omega-3 fatty acids on brain function. J Biomed Sci 2016; 23: 17. doi: 10.1186/s12929-016-0241-8.
    7. Zhang M, Han W, Hu S, et al. Methylcobalamin: A potential vitamin for pain killer. Neural Plast 2013; doi: 10.1155/2013/424651.
    8. Solomon LR. Functional vitamin B12 deficiency in advanced malignancy: implication for the management of neuropathy and neuropathic pain. Support Care Cancer 2016; 24(8); 3489-3494.
    9. Altman R, Bosch B, Burne K, et al. Advances in NASID development: Evolution of diclofenac products using pharmaceutical technology. Drugs 2015; 75(8): 859-877.
    10. Erfanparast A, Escort M, Tamaddonfard E, et al. Systemic and local peripheral injection of vitamin B12 suppresed orofacial nociception induced by formalin in rats. Drug Res (Stuttg) 2014; 64(2): 85-90.
    11. Narai Y, Imamachi N, Saito Y. Gabapentin augments the antihyperalgesic effects of diclofenac sodium through spinal action in a rat postoperative pain model.Anesth Analg 2012; 115(1): 189-193.
    12. Björkman RL, Hedner T, Hallman KM, et al.Localization of the central antinociceptive effects of diclofenac in the rat.Brain Res 1992; 590(1-2): 66-73.
    13. Björkman R. Central antinociceptive effects of non-steroidal anti-inflammatory drugs and paracetamol. Experimental studies in the rat. Acta Anesthesiol Scand Suppl 1995; 103: 1-44.
    14. Ghelardini C, di Cesare Mannelli L, Bianchi E. The pharmacological basis of opioids. Clin Cases Miner Bone Metab 2015; 12(3): 219-221.
    15. Bodnar RJ. Endogenous opiates and behavior: 2015. Peptides 2017; 88: 126-188.
    16. Erfanparast A, Tamaddonfard E, Nemati S. Effects of intra-hippocampal microinjection of vitamin B12 on the orofacial pain and memory impairments induced by scopolamine and orofacial pain. Physiol Behav 2017; 170: 68-77.
    17. Franca DS, Souza AL, Almeida KR, et al. B vitamins induce an antinociceptive effect in the acetic acid and formaldehyde models of nociception in mice. Eur J Pharmacol 2001; 421(3): 157-164.
    18. National Research Council (NRC). Committee for the update of the guide for care and use of laboratory animals. 8th ed. Washington, USA: National Academies Press, 2011; 11-41.
    19. Paxinos G,Watson C. The rat brain in stereotaxic coordinates. 6th ed. San Diego, USA: Elsevier Academic Press, 2007.
    20. Ghasemi H, Tamaddonfard E, Soltanalinejad F. Role of thalamic ventral posterolateral nucleus histamine and opiate receptors in modulation of formalin-induced muscle pain in rats. Pharmacol Rep 2017; 69(6): 1393-1401.
    21. Cortright DN, Matson DJ, Broom DC. New frontiers in assessing pain and analgesia in laboratory animals. Expert Opin Drug Discov 2008; 3(9): 1099-1108.
    22. Tamaddonfard E, Erfanparast A, Ghasemi H, et al. The role of histamine H1, H2 and H3 receptors of ventral posteromedial nucleus of thalamus in modulation of trigeminal pain. Eur J Pharmacol 2016; 791: 696-702.
    23. Tamaddonfard E, Erfanparast A, Taati M, et al. Role of opioid system in verapamil-induced antinociception in a rat model of orofacial pain. Vet Res Forum 2014; 5(1): 49-54.
    24. Tamaddonfard E, Hamzeh-Gooshchi N. Effects of administration of histamine and its H1, H2 and H3 receptor antagonists into the primary somatosensory cortex on inflammatory pain in rats. Iran J Basic Med Sci 2014; 17(1): 55-61.
    25. Porro CA, Cavazzuti M. Spatial and temporal aspects of spinal cord and brainstem activation in the formalin pain model. Prog Neurobiol 1993; 41(5): 565-607.
    26. Laurin J, Pertici V, Dousset E, et al. Group III and IV muscle afferents: Role on central motor drive and clinical implication. Neuroscience 2015; 290: 543-551.
    27. Mense S. Algesic agents exciting muscle nociceptors. Exp Brain Res 2009; 196(1): 89-100.
    28. Tamaddonfard E, Samadi F, Egdami K. The effects of vitamin B12 and their combination on cold and mechanical allodynia in a neuropathic pain model in rats. Vet Res Forum 2013; 4(1): 19-24.
    29. Hosseinzadeh H, Moallem S, Moshiri M, et al. Anti-nociception and anti-inflammatory effects of cyanocobalamine (vitamin B12) against acute and chronic pain and inflammation in rats. Arzneimittelforschung 2012; 62(7): 324-329.
    30. Gan TJ. Diclofenac: An update on its mechanism of action and safety profile. Curr Med Res Opin 2010; 26(7): 1715-1731.
    31. Gwanyanya A, Macianskiene R, Mubagwa K. Insights into the effects of diclofenac and other non-steroidal anti-inflammatory agents on ion channels. J Pharm Pharmacol 2012; 64(10): 1359-1375.
    32. Silva LC, Miranda e Castor MG, Souza TC, et al. NSAIDs induce peripheral antinociception by interaction with the adrenergic system. Life Sci 2015; 130: 7-11.
    33. Tamaddonfard E, Farshid AA, Samadi F, et al. Effect of vitamin B12 on functional recovery and histopathologic changes of tibial nerve-crushed rats. Drug Res (Stuttg) 2014; 64(9): 470-475.
    34. Trescot AM, Datta S, Lee M, et al. Opioid pharmacology. Pain Physician 2008; 11(2 Suppl): S133-S153.
    35. Kaneko K, Umehara M, Homan T, et al. The analgesic effect of tramadol in animal models of neuropathic pain and fibromyalgia. Neurosci Lett 2014; 562: 28-33.
    36. Sanchez EM, Bagues A, Martin MI. Contribution of peripheral and central opioid receptors to anti-nociception in rat muscle pain models. Pharmacol Biochem Behav 2010; 96(4): 488-495.
    37. Tsiklauri N, Nozadze I, Gwtskaia G, et al. Anti-nociceptive tolerance to NSAIDs in the rat formalin test is mediated by the opioid mechanisms. Pharmacol Rep 2017; 69(1): 168-175.
    38. Gorgiladze T, Nozadze I, Abzianidze E, et al. Non-steroidal anti-inflammatory drugsʼs antinociception mediated by the opioid mechanism in the nucleus raphe magnus. Georgian Med News 2017; 265:
      99-104.
Veterinary Research Forum
Volume 9, Issue 4
Autumn 2018
Pages 329-335

  • Receive Date 12 November 2018

Home

Guide for Authors

Submit Manuscript

Reviewers

Contact Us