Evaluation of Postoperative Anti-nociceptive Efficacy of Intrathecal Dexketoprofen in Rats

Year 2016, Volume: 33 Issue: 3, 245 - 251, 01.05.2016

Birol Muhammet Er İsmail Serhat Kocamanoğlu Ayhan Bozkurt Sırrı Bilge Erhan Çetin Çetinoğlu

Abstract

Background: Some studies have suggested that the intrathecal use of cyclooxygenase enzyme inhibitors provides an anti-nociceptive effect. Therefore, the occurrence of side effects seen in systemic usage can be eliminated. Aims: The primary objective of this experimental, randomized, controlled trial was to test the hypothesis asserting that intrathecal dexketoprofen trometamol would demonstrate an analgesic effect during postoperative period. Study Design: Animal experimentation. Methods: Forty rats were randomized into 4 groups 7 days after intrathecal catheterization; the following drugs were given through catheter lumens: Group Lidocaine (Group L): Lidocaine 20 μg; Group Lidocaine-Morphine (Group LM): Lidocaine 20 μg and morphine 0.5 μgr; Group Lidocaine-Dexketoprofen (Group LD): Lidocaine 20 μg and dexketoprofen trometamol 100 μg; and Group Dexketoprofen (Group D): Dexketoprofen trometamol 100 μg. Paw incision was achieved under ether inhalation. To measure analgesic potential, hot plate and tail immersion tests were used as nociceptive tests during the postoperative period. Results: The mean reaction times detected in groups during hot plate and tail immersion tests were shortest in Group L at 15, 30, 45, 60, 75, 90, 105, and 120 minutes after start of surgery (p<0.01, all others). In the groups using dexketoprofen, as in the morphine group, longer reaction times were detected than in the lidocaine group at all measurement times except 120 minutes (p<0.01). Conclusion: Intrathecal dexketoprofen in the optimal perioperative pain management is effective, and can be administered as an adjuvant in clinics after neurotoxicity studies in animals, and effective dose studies in volunteers.

Keywords

Dexketoprofen trometamol, injection, pain, postoperative, postoperative complications, spinal

References

• 1. Han JB, Keller EE, Grothe RM. Postoperative gastrointestinal bleeding in orthognathic surgery patients: its estimated prevalence and possible association to known risk factors. J Oral Maxillofac Surg 2014;72:2043-51. [CrossRef]
• 2. Yaksh TL, Dirig DM, Conway CM, Svensson C, Luo D, Isakson PC. The acute antihyperalgesic action of NSAIDs and release of spinal PGE2 is mediated by the inhibition of constitutive spinal COX-2 but not COX-1. J Neurosci 2001;21:5847-53.
• 3. Choi CH, Kim WM, Lee HG, Jeong CW, Kim CM, Lee SH, et al. Roles of opioid receptor subtype in the spinal antinociception of selective cyclooxygenase 2 inhibitor. Korean J Pain 2010;23:236-41. [CrossRef]
• 4. McCormack K. The spinal actions of nonsteroidal anti-inflammatory drugs and the dissociation between their anti-inflammatory and analgesic effects. Drugs 1994;47:28-45. [CrossRef]
• 5. Rodríguez MJ, Arbós RM, Amaro SR. Dexketoprofen trometamol: clinical evidence supporting its role as a painkiller. Expert Rev Neurother 2008;8:1625-40. [CrossRef]
• 6. Cabre F, Fernandez MF, Calvo L, Ferrer X, Garcia ML, Mauleon D. Analgesic, antiinflammatory and antipyretic effects of S(+)- ketoprofen in vivo. J Clin Pharmacol 1998;38:3S-10S.
• 7. Yaksh TL, Rudy TA. Analgesia mediated by a direct spinal action of narcotics. Science 1976;192:1357-8. [CrossRef]
• 8. Brennan TJ, Vandermeulen EP, Gebhart GF. Characterization of a rat model of incisional pain. Pain 1996;64:493-501. [CrossRef]
• 9. Spofford CM, Ashmawi H, Subieta A, Buevich F, Moses A, Baker M, et al. Ketoprofen produces modality-specific inhibition of pain behaviors in rats after plantar incision. Anesth Analg 2009;109:1992-9. [CrossRef]
• 10. Derry S, Derry CJ, Moore RA. Single dose oral ibuprofen plus oxycodone for acute postoperative pain in adults. Cochrane Database Syst Rev 2013;6:CD010289. [CrossRef]
• 11. Ding Y, White PF. Comparative effects of ketorolac, dezocine and fentanyl as adjuvants during outpatient anesthesia. Anesth Analg 1992;75:566-71. [CrossRef]
• 12. Moore RA, Barden J. Systematic review of dexketoprofen in acute and chronic pain. BMC Clin Pharmacol 2008;8:11. [CrossRef]
• 13. Souter A, Fredman B, White PF. Controversies in the perioperative use of nonsteroidal antiinflammatory drugs. Anesth Analg 1994;79:1178-90. [CrossRef]
• 14. Malmberg AB, Yaksh TL. Hyperalgesia mediated by spinalglutamate or substance P receptor blocked by spinal cyclooxygenase inhibition. Science 1992;257:1276-9. [CrossRef]
• 15. Willingale HL, Gardiner NJ, McLymont N, Giblett S, Grubb BD. Prostanoids synthesized by cyclooxygenase isoforms in rat spinal cord and their contribution to the development of neuronal hyperexcitability. Br J Pharmacol 1997;122:1593-604. [CrossRef]