Advertisement

Clinical blood gas indices and histopathological effects of intrathecal injection of tolfenamic acid and lidocaine Hcl in donkeys

Abstract

The present study aimed to investigate the clinical blood gas indices and histopathological consequences after intrathecal injection of tolfenamic acid and lidocaine Hcl and moreover, to elucidate the spinal safety of tolfenamic acid as a cyclooxygenase inhibitor in donkeys. Ten clinically healthy donkeys were divided into two groups, 5 animals each. The first group received lidocaine Hcl 2% and the second one received tolfenamic acid 4% intrathecally. The physical parameters and ataxia, analgesia, and motor blockade scores were recorded. Blood gases and acid base balance indices and histopathological examination were done. Blood pH level was significantly decreased (P < 0.05) and the blood pCO2 level was significantly increased (P < 0.05) 15 min after intrathecal injection of tolfenamic acid. Additionally, there was a significant difference in the motor block scores between the two groups at 2 and 4 h post-injection. Histopathological findings of the spinal cord of tolfenamic acid–injected group revealed neurodegeneration and necrosis which were manifested clinically by paraplegia. In conclusion, the present study uncovered the analgesic and motor effects of commercially prepared tolfenamic acid following intrathecal injection in donkeys. Nevertheless, it is unsafe because of its neurotoxic effect on the spinal cord which was manifested clinically by paraplegia of donkeys. On the other hand, intrathecal administration of lidocaine Hcl was safe and causes nonserious cardiopulmonary changes.

This is a preview of subscription content, log in to check access.

Access options

Buy single article

Instant unlimited access to the full article PDF.

US$ 39.95

Price includes VAT for USA

Subscribe to journal

Immediate online access to all issues from 2019. Subscription will auto renew annually.

US$ 99

This is the net price. Taxes to be calculated in checkout.

Fig. 1
Fig. 2
Fig. 3

References

  1. Aygün D, Kaplan S, Odaci E, Onger ME, Altunkaynak ME (2012) Toxicity of non-steroidal anti- inflammatory drugs: a review of melatonin and diclofenac sodium association. Histol Histopathol 27:417–436

  2. Brosnan RJ, Steffey EP, LeCouteur RA, Imai A, Farver TB, Kortz GD (2002) Effects of body position on intracranial and cerebral perfusion pressures in isoflurane-anesthetized horses. J Appl Physiol 92:2542–2546

  3. Buckenmaier C, Nielsen KC, Pietrobon R, Klein SM, Martin AH, Greengrass RA, Steele SM (2002) Small-dose intrathecal lidocaine versus ropivacaine for anorectal surgery in an ambulatory setting. Anesth Analg 95(5):1253–1257

  4. Budras K, Sack W, Röck R, Horowitz A, Berg R (2009) Anatomy of the horse. 5th ed., Schlütersche Verlagsgesellschaft mbH & Co. KG., Hans-Böckler-Alle 7, 30173 Hannover, Germany

  5. DeRossi R, Módolo T, Pagliosa R, Jardim P, Maciel F, Macedo GG (2012) Comparison of analgesic effects of caudal epidural 0.25% bupivacaine with bupivacaine plus morphine or bupivacaine plus ketamine for analgesia in conscious horses. J Equine Vet Sci 32:190–195

  6. Devoghel JC (1993) Intrathecal injection of lysine-acetylsalicylate in man with intractable cancer pain. In Progress in pharmacology and clinical pharmacology (Jurna I, Yaksh TL, Eds.); Vol. 10, pp. 111–118. Gustav Fischers Verlag

  7. Dolan S, Nolan AM (2000) Behavioural evidence supporting a differential role for group I and II metabotropic glutamate receptors in spinal nociceptive transmission. Neuropharmacology 39:1132–1138

  8. Duncanson G (2012) Veterinary treatment of sheep and goats. 1st ed. MPG Books Group, UK

  9. Fischer AH, Jacobson KA, Rose J, Zeller R (2008) Hematoxylin and eosin staining of tissue and cell sections. CSH Protoc

  10. Furr M, Reed S (2008) Equine neurology. Blackwell Publishing Ltd

  11. Greene SA (2002) Veterinary anesthesia and pain management secrets (. Ed.) 1st edition. HANLEY & BELFUS, INC. Medical Publishers 210 South 13th Street Philadelphia, PA 19107

  12. Hanson PD, Maddison JE (2008) Nonsteroidal anti-inflammatory drugs and chondroprotective agents. In. Small animal clinical pharmacology (Maddison, J. Editor) 2nd ed. Saunders, Elsevier. London; 287–307

  13. Hayta E, Elden H (2018) Acute spinal cord injury: a review of pathophysiology and potential of non-steroidal antiinflammatory drugs for pharmacological intervention. J Chem Neuroanat 87:25–31

  14. Jaussaud P, Guieu D, Bellon C, Barbier B, Lhopital MC, Sechet R, Courtot D, Toutain PL (1992) Pharmacokinetics of tolfenamic acid in the horse. Equine Vet J Suppl (11):69–72

  15. Jittreetat T, Shin YS, Hwang HS, Lee BS, Kim YS, Sannikorn P, Kim CH (2016) Tolfenamic acid inhibits the proliferation, migration, and invasion of nasopharyngeal carcinoma: involvement of p38-mediated down-regulation of slug. Yonsei Med J 57(3):588–598

  16. Kang SU, Shin YS, Hwang HS, Baek SJ, Lee SH, Kim CH (2012) Tolfenamic acid induces apoptosis and growth inhibition in head and neck cancer: involvement of NAG-1 expression. PLoS One 7(4):e34988

  17. Kasibhatla S, Amarante-Mendes GP, Finucane D, Brunner T, Bossy-Wetzel E, Green DR (2006) Acridine Orange/ethidium bromide (AO/EB) staining to detect apoptosis. CSH Protoc

  18. Lees P (2009) Analgesic, antiinflammatory, antipyretic drugs. In.Veterinary pharmacology and therapeutics (Riviere, J; Papich, M. and Adams, H.R. Editors). Ninth ed. Willey-Blackwell. USA; 457–492

  19. Lees P (2018) Analgesic, antiinflammatory, antipyretic drugs. In. (Veterinary pharmacology and therapeutics Riviere, J.E and Papich, M.G. Eds) tenth edition. Wiley Blackwell. PP. 467–500

  20. Lefebvre HP, Laroute V, Alvinerie M, Schneider M, Vinclair P, Braun JP, Toutain PL (1997) The effect of experimental renal failure on tolfenamic acid disposition in the dog. Biopharm Drug Dispos 18(1):79–91

  21. Malmberg AB, Yaksh TL (1992) Antinociceptive actions of spinal nonsteroidal anti-inflammatory agents on the formalin test in the rat. J Pharmacol Exp Ther 263:136–146

  22. Muir W (2009) Anxiolytics, Nonopioid sedative-analgesics, and opioid analgesics. In. Equine anesthesia: monitoring and emergency therapy (Muir, W and Hubbell, J. Eds), 2nd ed. Saunders, Elsevier, USA; 185–209

  23. Plumb D (2011) Plumb’s veterinary drug handbook. 7th ed. PharmaVet Inc., Stockholm

  24. Robinson EP, Natalini CC (2002) Epidural anesthesia and analgesia in horses. Vet Clin North Am (Equine Pract) 18(1):61–82

  25. Samad TA, Moore KA, Sapirstein A, Billet S, Allchorne A, Poole S, Bonventre JV, Woolf CJ (2001) Interleukin-1β-mediated induction of cox-2 in the CNS contributes to inflammatory pain hypersensitivity. Nature 410:471–475

  26. Sams RA, Muir W (2009) Principles of drug disposition and drug interaction in horse. In. Equine anesthesia: monitoring and emergency therapy. 2nd ed. SAUNDERS ELSEVIER. 11830 Westline industrial drive. St. Louis, Missouri 63146. PP. 171–184

  27. Sankpal UT, Lee CM, Connelly SF, Kayaleh O, Eslin D, Sutphin R, Goodison S, Adwan L, Zawia NH, Lichtenberger LM, Basha R (2013) Cellular and organismal toxicity of the anti-cancer small molecule, tolfenamic acid: a pre-clinical evaluation. Cell Physiol Biochem 32:675–686

  28. Scott DB (1986) Toxic effects of local anaesthetic agents on the central nervous system. Br J Anaesth 58:732–735

  29. Sidhu PK (2006) Pharmacokinetic and pharmacodynamic interactions of tolfenamic acid and marbofloxacin in goats. Res Vet Sci 80:79–90

  30. Sidhu PK, Landoni MF, Lees P (2005) Influence of marbofloxacin on the pharmacokinetics and pharmacodynamics of tolfenamic acid in calves. J Vet Pharmacol Ther 28:109–119

  31. Sidhu PK, Landoni MF, Lees P (2006) Pharmacokinetic and pharmacodynamic interactions of tolfenamic acid and marbofloxacin in goats. Res Vet Sci 80(1):79–90

  32. Skarda RT, Muir WW, Ibrahim AL (1985) Spinal fluid concentrations of mepivacaine in horses and procaine in cows after thoracolumbar subarachnoid analgesia. Am J Vet Res 46:1020–1024

  33. Skarda RT, Muir W, Hubbell JAE (2009) Local anesthetic drugs and techniques. In. Equine anesthesia: monitoring and emergency therapy (Muir, W. and Hubbell J. Eds.) 2nd ed., Saunders, Elsevier. St. Louis, Missouri 63146. USA; 210–242

  34. Staffieri F, Driessen B, Lacitignolas L, Crovace A (2009) A comparison of subarachnoid buprenorphine or xylazine as an adjunct to lidocaine for analgesia in goats. Vet Anaesth Analg 36:502–511

  35. Svensson CI, Yaksh TL (2002) The spinal phospholipase-cyclooxygenase-prostanoid cascade in nociceptive processing. Annu Rev Pharmacol Toxicol 42:553–583

  36. Taylor FGR, Brazil T, Hillyer MH (2010) Diagnostic techniques in equine medicine. 2nd edition. Saunders Elsevier; 303

  37. Yahia D, Abd El-Hakiem M (2014) Biochemical analysis of synovial fluid, cerebrospinal fluid and vitreous humor at early postmortem intervals in donkeys. J Adv Vet Res 4(1):6–11

  38. Yaksh TL, Horais KA, Tozier N, Rathbun M, Richter P, Rossi S, Grafe M, Tong C, Meschter C, Cline JM, Eisenach J (2004) Intrathecal ketorolac in dogs and rats. Toxicol Sci 80(2):322–334

  39. Yamashita A, Matsumoto M, Matsumoto S, Itoh M, Kawai K, Sakabe T (2003) A comparison of the neurotoxic effects on the spinal cord of tetracaine, lidocaine, bupivacaine, and ropivacaine administered intrathecally in rabbits. Anesth Analg 97(2):512–519

Download references

Author information

Correspondence to Abdelbaset Eweda Abdelbaset.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

The experimental protocol of the current study was approved by the Animal Care and Ethics Committee of Assiut University, Assiut, Egypt.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Abdelhakiem, M.A.H., Abdelbaset, A.E., Abd-Elkareem, M. et al. Clinical blood gas indices and histopathological effects of intrathecal injection of tolfenamic acid and lidocaine Hcl in donkeys. Comp Clin Pathol 29, 83–93 (2020) doi:10.1007/s00580-019-03025-7

Download citation

Keywords

  • Analgesia
  • Blood gases
  • Intrathecal
  • Tolfenamic acid
  • Lidocaine Hcl
  • Donkeys