Comparative efficacy of pregabalin and baclofen in the rodent chronic constriction injury model of neuropathic pain

Saurabh Kohli, Taruna Sharma, Juhi Kalra, Dilip C. Dhasmana


Background: Neuropathic pain is associated with prolonged disability and is usually not responsive to conventional analgesics like NSAIDs and opioids. Even the recommended first-line drugs are effective in less than 50% patients. Thus, drugs with different mechanisms of action are needed. Baclofen, a GABA-B agonist has shown benefit in different types of neuropathic pains and is compared against pregabalin.

Methods: The sciatic nerve was ligated in 2 groups of 6 rats each as per the chronic constriction injury model of neuropathic pain on day 0. After 14 days the effect of single doses of pregabalin (30mg/kg) and baclofen (5mg/kg) intraperitoneally were assessed over a 2 hours period. Thermal and mechanical hyperalgesia were assessed as measures of neuropathic pain by the hotplate and pin-prick method respectively.

Results: Significant thermal and mechanical hyperalgesia was produced 14 days after sciatic nerve ligation in both the groups (p <0.05). Both pregabalin (p <0.001) and baclofen (p <0.01) were effective in decreasing thermal hyperalgesia throughout the two hours study period, but pregabalin was more effective as compared to baclofen (p <0.05) at 30, 60 and 120minutes. Both the drugs produced a significant decrease in mechanical hyperalgesia (p <0.01) throughout the study period. Again, pregabalin was the more effective drug (p <0.05) at all time points.

Conclusions: Significant thermal and mechanical hyperalgesia was seen 14 days after sciatic nerve ligation. Both pregabalin and baclofen were effective in reversing the hyperalgesia, but pregabalin was the more effective of the two drugs at all time points.


Baclofen, Chronic constriction injury, Neuropathic pain, Pregabalin

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Salter MW. Deepening understanding of the neural substrates of chronic pain. Brain. 2014 Feb 17;137(3):651-3.

Costigan M, Scholz J, Woolf CJ. Neuropathic pain: a maladaptive response of the nervous system to damage. Annual Rev Neurosci. 2009 Jul 21;32:1-32.

Bouhassira D, Attal N. Translational neuropathic pain research: a clinical perspective. Neurosci. 2016 Dec 3;338:27-35.

Alles SR, Smith PA. Etiology and pharmacology of neuropathic pain. Pharmacol Rev. 2018 Apr 1;70(2):315-47.

Jensen TS, Baron R, Haanpää M, Kalso E, Loeser JD, Rice AS, et al. A new definition of neuropathic pain. Pain. 2011 Oct;152(10):2204-5.

Schmidt BL, Hamamoto DT, Simone DA, Wilcox GL. Mechanism of cancer pain. Molecular Intervent. 2010 Jun;10(3):164.

Yekkirala AS, Roberson DP, Bean BP, Woolf CJ. Breaking barriers to novel analgesic drug development. Nature Rev Drug Discovery. 2017 Aug;16(8):545.

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 Feb 1;14(2):162-73.

Colleoni M, Sacerdote P. Murine models of human neuropathic pain. Biochimica et Biophysica Acta (BBA)-Molecular Basis Dis. 2010 Oct 1;1802(10):924-33.

Bennett GJ, Xie YK. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain. 1988 Apr 1;33(1):87-107.

Wanj LX, Wanj ZJ. Animal and cellular models of chronic pain. Adv Drug Delivery Rev. 2003; 5:949-65.

Vogel GH, Vogel WGH, editors, Drug discovery and evaluation- pharmacological assays. 2nd ed. New York: Verlog Springer publication; 1996.

Wang YX, Bowersox SS, Pettus M, Gao DA. Antinociceptive properties of fenfluramine, a serotonin reuptake inhibitor, in a rat model of neuropathy. J Pharmacol Experimental Therapeut. 1999 Dec 1;291(3):1008-16.

Gonzalez MI, Field MJ, Hughes J, Singh L. Evaluation of selective NK1 receptor antagonist CI-1021 in animal models of inflammatory and neuropathic pain. J Pharmacol Experiment Therapeut. 2000 Aug 1;294(2):444-50.

Chen SR, Xu Z, Pan HL. Stereospecific effect of pregabalin on ectopic afferent discharges and neuropathic pain induced by sciatic nerve ligation in rats. Anesthesiology: J Am Soc Anesthesiologists. 2001 Dec 1;95(6):1473-9.

Field MJ, McCleary S, Hughes J, Singh L. Gabapentin and pregabalin, but not morphine and amitriptyline, block both static and dynamic components of mechanical allodynia induced by streptozocin in the rat. Pain. 1999 Mar 1;80(1-2):391-8.

Jones DL, Sorkin LS. Systemic gabapentin and S (+)-3-isobutyl-γ-aminobutyric acid block secondary hyperalgesia. Brain Res. 1998 Nov 9;810(1-2):93-9.

Gilron I, Flatters SJ. Gabapentin and pregabalin for the treatment of neuropathic pain: A review of laboratory and clinical evidence. Pain Res Management. 2006;11(Suppl A):16A-29A.

Dworkin RH, O’Connor AB, Audette J, Baron R, Gourlay GK, Haanpaa ML, et al. Recommendations for the pharmacological management of neuropathic pain: an overview and literature update. InMayo Clin Proc. 2010;85(3):S3-S14.

FDA. Highlights of prescribing information Lyrica (Pregabalin). Available at: Accessed 09 October 2018.

Franek M, Vaculin S, Rokyta R. GABA~ B receptor agonist baclofen has non-specific antinociceptive effect in the model of peripheral neuropathy in rat. Physiological Res. 2004 Jan 1;53:351-5.

Smith TE, Chong MS. Neuropathic pain. Hospital Med. 2000;6:760-6.

Santos TJF, Castro-Costa CM, Giffoni SDA, Santos FJC, Ramos RSN, Gifoni MAC. The effect of baclofen on spontaneous and evoked behavioural expression of experimental neuropathic chronic pain. Arq Neuropsiquiatr. 1999;57(3):753-760.

Attal N, Cruccu G, Haanpää M, Hansson P, Jensen TS, Nurmikko T, et al. EFNS guidelines on pharmacological treatment of neuropathic pain. Eur J Neurol. 2006 Nov;13(11):1153-69.