DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20172251

Evaluation of analgesic and anti-inflammatory activity of a combination of tramadol-pregabalin in animal models of pain and inflammation

Suthakaran C., Raja T. A. R., Kayalvizhi M. K., Nithya K., Ramnarayana Reddy R. V.

Abstract


Background: A major goal of pain management is to provide pain relief that is clinically meaningful, sustained, and associated with minimum and reversible adverse effects. Since single analgesic drug is not effective in all patients, there is a need either to develop new and more effective drugs or to identify favourable combinations of drugs that are already available. The aim of the present was to evaluate the analgesic and anti-inflammatory activity of tramadol and pregabalin when used alone or in combination in animal models of pain and inflammation.

Methods: The animals (rats and mice) were divided into eight groups with six animals in each group. Analgesia was assessed by acetic acid induced writhing and tail flick methods in mice and hot plate method in rats. Paw oedema model in rats after induction with 0.1 ml of 1% carrageenan was used to assess the anti‑inflammatory activity. The percentage inhibition of writhes and prolongation of reaction time were used for assessing analgesic activity and reduction in paw volume was used for assessing anti-inflammatory activity. The results obtained were analysed by ANOVA and Tukey HSD Post-hoc Test.

Results: Treatment with tramadol pregabalin alone or in combination reduced writhing episodes significantly in acetic acid induced writhing in mice as compared to control indicating its analgesic effect and the highest percentage inhibition of pain was seen with high dose tramadol plus pregabalin. Treatment in Hot plate and Tail flick methods significantly prolonged the reaction time at all time points.

Conclusions: Tramadol when combined with pregabalin may enhance its anti-nociceptive effects. If confirmed in additional models of acute and/or chronic pain this combination might be useful in the clinical management of pain not associated with inflammation.


Keywords


Combination analgesia, Pain, Pregabalin, Tramadol

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References


Rocha AP, Kraychete DC, Lemonica L, de Carvalho LR, de Barros GA, Garcia JB, et al. Pain: current aspects on peripheral and central sensitization. Rev Bras Anestesiol. 2007 Feb;57(1):94-105.

Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. 2011 Mar;152(3):S2-15.

Latremoliere A, Woolf CJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain. 2009 Sep;10(9):895-926.

Derry S, Wiffen PJ, Moore RA. Relative efficacy of oral analgesics after third molar extraction: a 2011 update. Br Dent J. 2011 Nov 11; 211(9):419-20.

Bauer CS, Nieto-Rostro M, Rahman W, Tran-Van-Minh A, Ferron L, Douglas L, et al. The increased trafficking of the calcium channel subunit alpha2delta-1 to presynaptic terminals in neuropathic pain is inhibited by the alpha2delta ligand pregabalin. J Neurosci. 2009 Apr 1;29(13):4076-88.

Stahl SM, Porreca F, Taylor CP, Cheung R, Thorpe AJ, Clair A. The diverse therapeutic actions of pregabalin: is a single mechanism responsible for several pharmacological activities? Trends Pharmacol Sci. 2013 Jun;34(6):332-9.

Zhang J, Ho KY, Wang Y. Efficacy of pregabalin in acute postoperative pain: a meta-analysis. Br J Anaesth. 2011 Apr;106(4):454-62.

Frampton JE, Foster RH. Pregabalin: in the treatment of postherpetic neuralgia. Drugs. 2005;65(1):111-8.

Mishriky BM, Waldron NH, Habib AS. Impact of pregabalin on acute and persistent postoperative pain: a systematic review and meta-analysis. Br J Anaesth. 2015 Jan;114(1):10-31.

Scott LJ, Perry CM. Tramadol: a review of its use in perioperative pain. Drugs. 2000;60:139-76.

Dhillon S. Tramadol/paracetamol fixed-dose combination: a review of its use in the management of moderate to severe pain. Clin Drug Investig. 2010;30(10):711-38.

Pergolizzi JV, van de Laar M, Langford R, Mellinghoff HU, Merchante IM, Nalamachu S, et al. Tramadol/paracetamol fixed-dose combination in the treatment of moderate to severe pain. J Pain Res. 2012;5:327-46.

Tripathi S, Shah R, Sharma DC. Analgesic activity of fixed dose combinations of paracetamol with diclofenac sodium and paracetamol with tramadol on different pain models in healthy volunteers: A randomized double blind crossover study. J Anaesthesiol Clin Pharmacol. 2012 Oct;28(4):465-9.

Suthakaran C, Kayalvizhi MK, Nithya K, Raja TAR. Evaluation of analgesic and anti-inflammatory tramadol-ibuprofen in experimental animals. Ind J Dental Res. 2017;28:(In Press).

Koster R, Anderson M, de Beer EJ. Acetic acid for analgesic screening. Fed Proc. 1959;18:412.

Luttinger D. Determination of antinociceptive efficacy of drugs in mice using different water temperatures in a tail-immersion test. J Pharmacol Methods. 1985 Jul;13(4):351-7.

Pinardi G, Sierralta F, Miranda HF. Atropine reverses the antinociception of nonsteroidal anti-inflammatory drugs in the tail-flick test of mice. Pharmacol Biochem Behav. 2003 Feb;74(3):603-8.

Eddy NB, Leimbach D. Synthetic analgesics. II. Dithienylbutenyl- and dithienylbutyl amines. J Pharmacol Exp Ther. 1953 Mar;107(3):385-93.

Winter CA, Risley EA, Nuss GW. Carrageenan-induced oedema in hind paw of the rat as an assay for anti-inflammatory drugs. Proc Soc Exp Biol Med. 1962 Dec;111:544-7.

Singh H, Ghosh MN. Modified plethysmometer for measuring foot volume of unanesthetized rats. J Pharm Pharmacol. 1968 Apr;20(4):316-7.

Smith HS. Combination opioid analgesics. Pain Physician. 2008 Mar-Apr;11(2):201-14.

Langerman L, Zakowski MI, Piskoun B, Grant GJ. Hot plate versus tail flick: evaluation of acute tolerance to continuous morphine infusion in the rat model. J Pharmacol Toxicol Methods. 1995 Sep;34(1):23-7.

Raffa RB. Pharmacology of oral combination analgesics: rational therapy for pain. J Clin Pharm Ther. 2001 Aug;26(4):257-64.

Dahl JB, Nielsen RV, Wetterslev J, Nikolajsen L, Hamunen K, Kontinen VK et al. Post-operative analgesic effects of paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations: a topical review. Acta Anaesthesiol Scand. 2014 Nov;58(10):1165-81.