The Korean Journal of Pain

The Korean Pain Society (대한통증학회)
권호 표지
DOI QR코드

DOI QR Code

Pharmacological interactions between intrathecal pregabalin plus tianeptine or clopidogrel in a rat model of neuropathic pain

  • Lee, Hyung Gon (Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School) ;
  • Kim, Yeo Ok (Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School) ;
  • Choi, Jeong Il (Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School) ;
  • Han, Xue Hao (Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School) ;
  • Shin, Yang Un (Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School) ;
  • Yoon, Myung Ha (Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School)
  • Received : 2021.10.15
  • Accepted : 2021.11.29
  • Published : 2022.01.01
Download PDF
⟨ Previous Next ⟩

Abstract

Background: There is still unmet need in treating neuropathic pain and increasing awareness regarding the use of drug combinations to increase the effectiveness of treatment and reduce adverse effects in patients with neuropathic pain. Methods: This study was performed to determine the individual and combined effects of pregabalin, tianeptine, and clopidogrel in a rat model of neuropathic pain. The model was created by ligation of the L5-L6 spinal nerve in male Sprague-Dawley rats; mechanical allodynia was confirmed using von Frey filaments. Drugs were administered to the intrathecal space and mechanical allodynia was assessed; drug interactions were estimated by isobolographic or fixed-dose analyses. Results: Intrathecal pregabalin and tianeptine increased the mechanical withdrawal threshold in a dose-dependent manner, but intrathecal clopidogrel had little effect on the mechanical withdrawal threshold. An additive effect was noted between pregabalin and tianeptine, but not between pregabalin and clopidogrel. Conclusions: These findings suggest that intrathecal coadministration of pregabalin and tianeptine effectively attenuated mechanical allodynia in the rat model of neuropathic pain. Thus, pregabalin plus tianeptine may be a valid option to enhance the efficacy of neuropathic pain treatment.

Keywords

Acknowledgement

This study was supported by a grant (BCRI18027-1) of Chonnam National University Hospital Biomedical Research Institute.

References

  1. IASP. Taxonomy: neuropathic pain [Internet]. Washington, D.C.: IASP; 2017. Available at: https://www.iasp-pain.org/resources/terminology/?ItemNumber=1698#Neuropathicpain.
  2. I ASP. Epidermiolog y of neuropat hic pain: how common is neuropathic pain, and what is its impact? [Internet]. Washington, D.C.: IASP; 2014. Available at: https://www.iasp-pain.org/advocacy/global-year/neuropathicpain/?itemNumber=3934.
  3. Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol 2015; 14: 162-73. https://doi.org/10.1016/S1474-4422(14)70251-0
  4. Derry S, Bell RF, Straube S, Wiffen PJ, Aldington D, Moore RA. Pregabalin for neuropathic pain in adults. Cochrane Database Syst Rev 2019; 1: CD007076.
  5. Heo BH, Shin JY, Park KS, Lee HG, Choi JI, Yoon MH, et al. Effects of tianeptine on the development and maintenance of mechanical allodynia in a rat model of neuropathic pain. Neurosci Lett 2016; 633: 82-6. https://doi.org/10.1016/j.neulet.2016.09.022
  6. Tozaki-Saitoh H, Tsuda M, Miyata H, Ueda K, Kohsaka S, Inoue K. P2Y12 receptors in spinal microglia are required for neuropathic pain after peripheral nerve injury. J Neurosci 2008; 28: 4949-56. https://doi.org/10.1523/JNEUROSCI.0323-08.2008
  7. Yu T, Zhang X, Shi H, Tian J, Sun L, Hu X, et al. P2Y12 regulates microglia activation and excitatory synaptic transmission in spinal lamina II neurons during neuropathic pain in rodents. Cell Death Dis 2019; 10: 165. https://doi.org/10.1038/s41419-019-1425-4
  8. Kim SH, Chung JM. An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 1992; 50: 355-63. https://doi.org/10.1016/0304-3959(92)90041-9
  9. Yaksh TL, Rudy TA. Chronic catheterization of the spinal subarachnoid space. Physiol Behav 1976; 17: 1031-6. https://doi.org/10.1016/0031-9384(76)90029-9
  10. Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL. Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 1994; 53: 55-63. https://doi.org/10.1016/0165-0270(94)90144-9
  11. Yoon MH, Choi JI, Kwak SH. Characteristic of interactions between intrathecal gabapentin and either clonidine or neostigmine in the formalin test. Anesth Analg 2004 ;98: 1374-9. https://doi.org/10.1213/01.ANE.0000107937.00902.FC
  12. Yoon MH, Choi JI, Jeong SW. Antinociception of intrathecal cholinesterase inhibitors and cholinergic receptors in rats. Acta Anaesthesiol Scand 2003; 47: 1079-84. https://doi.org/10.1034/j.1399-6576.2003.00212.x
  13. Tallarida RJ. Drug synergism and dose-effect data analysis. Boca Raton, Chapman and Hall/CRC. 2000.
  14. Colloca L, Ludman T, Bouhassira D, Baron R, Dickenson AH, Yarnitsky D, et al. Neuropathic pain. Nat Rev Dis Primers 2017; 3: 17002. https://doi.org/10.1038/nrdp.2017.2
  15. Tallarida RJ. Quantitative methods for assessing drug synergism. Genes Cancer 2011; 2: 1003-8. https://doi.org/10.1177/1947601912440575
  16. Salat K, Librowski T, Nawiesniak B, Gluch-Lutwin M. Evaluation of analgesic, antioxidant, cytotoxic and metabolic effects of pregabalin for the use in neuropathic pain. Neurol Res 2013; 35: 948-58. https://doi.org/10.1179/1743132813Y.0000000236
  17. Zhang SS, Wu Z, Zhang LC, Zhang Z, Chen RP, Huang YH, et al. Efficacy and safety of pregabalin for treating painful diabetic peripheral neuropathy: a meta-analysis. Acta Anaesthesiol Scand 2015; 59: 147-59. https://doi.org/10.1111/aas.12420
  18. Verma V, Singh N, Singh Jaggi A. Pregabalin in neuropathic pain: evidences and possible mechanisms. Curr Neuropharmacol 2014; 12: 44-56. https://doi.org/10.2174/1570159X1201140117162802
  19. Belliotti TR, Capiris T, Ekhato IV, Kinsora JJ, Field MJ, Heffner TG, et al. Structure-activity relationships of pregabalin and analogues that target the alpha(2)-delta protein. J Med Chem 2005; 48: 2294-307. https://doi.org/10.1021/jm049762l
  20. Ben-Menachem E. Pregabalin pharmacology and its relevance to clinical practice. Epilepsia 2004; 45 Suppl 6: 13-8. https://doi.org/10.1111/j.0013-9580.2004.455003.x
  21. Sindrup SH, Otto M, Finnerup NB, Jensen TS. Antidepressants in the treatment of neuropathic pain. Basic Clin Pharmacol Toxicol 2005; 96: 399-409. https://doi.org/10.1111/j.1742-7843.2005.pto_96696601.x
  22. Lee HG, Choi JI, Yoon MH, Obata H, Saito S, Kim WM. The antiallodynic effect of intrathecal tianeptine is exerted by increased serotonin and norepinephrine in the spinal dorsal horn. Neurosci Lett 2014; 583: 103-7. https://doi.org/10.1016/j.neulet.2014.09.022
  23. Uzbay TI. Tianeptine: potential influences on neuroplasticity and novel pharmacological effects. Prog Neuropsychopharmacol Biol Psychiatry 2008; 32: 915-24. https://doi.org/10.1016/j.pnpbp.2007.08.007
  24. Bilge SS, Ilkaya F, Darakci O, Ciftcioglu E, Bozkurt A. Opioid receptors contribute to antinociceptive effect of tianeptine on colorectal distension-induced visceral pain in rats. Pharmacology 2018; 101: 96-103. https://doi.org/10.1159/000484207
  25. Jung YH, Kim YO, Han JH, Kim YC, Yoon MH. Isobolographic analysis of drug combinations with intrathecal BRL52537 (κ-opioid agonist), pregabalin (calcium channel modulator), AF 353 (P2X3 receptor antagonist), and A804598 (P2X7 receptor antagonist) in neuropathic rats. Anesth Analg 2017; 125: 670-7. https://doi.org/10.1213/ANE.0000000000001883
  26. Yoon MH, Bae HB, Choi JI, Jeong SW, Chung SS, Yoo KY, et al. Evaluation of interaction between intrathecal adenosine and MK801 or NBQX in a rat formalin pain model. Pharmacology 2005; 75: 157-64. https://doi.org/10.1159/000088345
  27. Yoon MH, Choi JI, Jeong SW. Spinal gabapentin and antinociception: mechanisms of action. J Korean Med Sci 2003; 18: 255-61. https://doi.org/10.3346/jkms.2003.18.2.255