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Current Drug Safety

Author(s): Manzumeh-Shamsi Meymandi, Gholamreza Sepehri*, Amirhossein Moslemizadeh and Seyyed Sajjad Vakili Shahrbabaki

DOI: 10.2174/1574886315666200628114257

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Prenatal Pregabalin Exposure Alters Postnatal Pain Sensitivity and Some Behavioral Responses in Adult Offspring Rats

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Abstract

Background: Prenatal antiepileptic drug exposure could demonstrate both congenital malformations and behavioral impairments in offspring.

Objective: This study was performed to assess the effects of prenatal exposure to pregabalin (PGB) on pain response, anxiety, motor activity and some behavior of adult offspring rats.

Methods: Pregnant Wistar rats received PGB (7.5, 15 and 30 mg/kg/ip) during embryonic days 9.5- 15.5. The pain response, anxiety-like behaviors, locomotor activity, motor balance and coordination and anhedonia of adult offspring were examined by tail-flick and hot plate test, open field test, elevated plus maze (EPM), beam balance test and sucrose preference test in their 60th day of life, respectively.

Results: Prenatal exposure to PGB revealed significant dose-dependent reduction in pain sensitivity (increase in pain latency response) in the hot plate test, especially in females, while anxiety-like behavior assessed in EPM and open field significantly reduced in males. In the open field, locomotor activity reduced significantly after exposure to PGB 30 mg/kg and motor coordination decreased dose-dependently, especially in males. Anhedonia, as an indication of sucrose preference or pleasure response, was not changed.

Conclusion: These findings suggest that prenatal PGB exposure could be associated with significant changes in pain response, anxiety, locomotor activity and coordination in adult offspring rats.

Keywords: Maternal exposure, pregabalin, behavior, pain, locomotor activity, rat.

Graphical Abstract

[1]
French J, Brandt C, Friedman D, et al. Adjunctive use of controlled-release pregabalin in adults with treatment-resistant partial seizures: A double-blind, randomized, placebo-controlled trial. Epilepsia 2014; 55(8): 1220-8.
[http://dx.doi.org/10.1111/epi.12690] [PMID: 24962242]
[2]
Zamani G, Tavasoli A, Zare-Shahabadi A, Rezaei N, Ahmadvand A. Efficacy of pregabalin in childhood refractory partial seizure. Iran J Pediatr 2014; 24(1): 100-4.
[PMID: 25793053]
[3]
Kanner AM, Ashman E, Gloss D, et al. Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs II: Treatment-resistant epilepsy: Report of the guideline development, dissemination, and implementation subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology 2018; 91(2): 82-90.
[http://dx.doi.org/10.1212/WNL.0000000000005756] [PMID: 29898974]
[4]
Patorno E, Bateman BT, Huybrechts KF, et al. Pregabalin use early in pregnancy and the risk of major congenital malformations. Neurology 2017; 88(21): 2020-5.
[http://dx.doi.org/10.1212/WNL.0000000000003959] [PMID: 28446648]
[5]
Bockbrader HN, Burger P, Knapp L, Corrigan BW. Population pharmacokinetics of pregabalin in healthy subjects and patients with chronic pain or partial seizures. Epilepsia 2011; 52(2): 248-57.
[http://dx.doi.org/10.1111/j.1528-1167.2010.02933.x] [PMID: 21269291]
[6]
Verma V, Singh N, Singh Jaggi A. Pregabalin in neuropathic pain: Evidences and possible mechanisms. Curr Neuropharmacol 2014; 12(1): 44-56.
[http://dx.doi.org/10.2174/1570159X1201140117162802] [PMID: 24533015]
[7]
Baldwin DS, den Boer JA, Lyndon G, Emir B, Schweizer E, Haswell H. Efficacy and safety of pregabalin in generalised anxiety disorder: A critical review of the literature. J Psychopharmacol (Oxford) 2015; 29(10): 1047-60.
[http://dx.doi.org/10.1177/0269881115598411] [PMID: 26259772]
[8]
Griffin E, Brown JN. Pregabalin for the treatment of restless legs syndrome. Ann Pharmacother 2016; 50(7): 586-91.
[http://dx.doi.org/10.1177/1060028016643097] [PMID: 27091870]
[9]
Gilron I, Jensen TS, Dickenson AH. Combination pharmacotherapy for management of chronic pain: From bench to bedside. Lancet Neurol 2013; 12(11): 1084-95.
[http://dx.doi.org/10.1016/S1474-4422(13)70193-5] [PMID: 24074723]
[10]
Meymandi M-S, Sepehri G, Abdolsamadi M, et al. The effects of co-administration of pregabalin and vitamin E on neuropathic pain induced by partial sciatic nerve ligation in male rats. Inflammopharmacology 2017; 25(2): 237-46.
[http://dx.doi.org/10.1007/s10787-017-0325-4] [PMID: 28233159]
[11]
Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: A systematic review and meta-analysis. Lancet Neurol 2015; 14(2): 162-73.
[http://dx.doi.org/10.1016/S1474-4422(14)70251-0] [PMID: 25575710]
[12]
Winterfeld U, Merlob P, Baud D, et al. Pregnancy outcome following maternal exposure to pregabalin may call for concern. Neurology 2016; 86(24): 2251-7.
[http://dx.doi.org/10.1212/WNL.0000000000002767] [PMID: 27194385]
[13]
Etemad L, Mohammad A, Mohammadpour AH, Vahdati Mashhadi N, Moallem SA. Teratogenic effects of pregabalin in mice. Iran J Basic Med Sci 2013; 16(10): 1065-70.
[PMID: 24379963]
[14]
Loring DW, Marino S, Meador KJ. Neuropsychological and behavioral effects of antiepilepsy drugs. Neuropsychol Rev 2007; 17(4): 413-25.
[http://dx.doi.org/10.1007/s11065-007-9043-9] [PMID: 17943448]
[15]
Meador KJ, Baker GA, Browning N, et al. NEAD Study Group. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): A prospective observational study. Lancet Neurol 2013; 12(3): 244-52.
[http://dx.doi.org/10.1016/S1474-4422(12)70323-X] [PMID: 23352199]
[16]
Bromley RL, Baker GA. Fetal antiepileptic drug exposure and cognitive outcomes. Seizure 2017; 44: 225-31.
[http://dx.doi.org/10.1016/j.seizure.2016.10.006] [PMID: 27784632]
[17]
Mølgaard-Nielsen D, Hviid A. Newer-generation antiepileptic drugs and the risk of major birth defects. JAMA 2011; 305(19): 1996-2002.
[http://dx.doi.org/10.1001/jama.2011.624] [PMID: 21586715]
[18]
Veiby G, Daltveit AK, Engelsen BA, Gilhus NE. Fetal growth restriction and birth defects with newer and older antiepileptic drugs during pregnancy. J Neurol 2014; 261(3): 579-88.
[http://dx.doi.org/10.1007/s00415-013-7239-x] [PMID: 24449062]
[19]
Salimzade A, Hosseini-Sharifabad A, Rabbani M. Comparative effects of chronic administrations of gabapentin, pregabalin and baclofen on rat memory using object recognition test. Res Pharm Sci 2017; 12(3): 204-10.
[http://dx.doi.org/10.4103/1735-5362.207201] [PMID: 28626478]
[20]
Nagkirshna L, Tamma N, Tadvi N, et al. Evaluation of protective of Vitamin-E on Vincristine induced peripheral neuropathy in Albino Rats. J Eva Med Dental Sci 2013; 2(15): 2538.
[http://dx.doi.org/10.14260/JEMDS/574]
[21]
Riga D, Theijs JT, De Vries TJ, Smit AB, Spijker S. Social defeat-induced anhedonia: effects on operant sucrose-seeking behavior. Front Behav Neurosci 2015; 9: 195.
[http://dx.doi.org/10.3389/fnbeh.2015.00195] [PMID: 26300748]
[22]
Morse DC, Henck JW, Bailey SA. Developmental toxicity studies with pregabalin in rats: significance of alterations in skull bone morphology. Birth Defects Res B Dev Reprod Toxicol 2016; 107(2): 94-107.
[http://dx.doi.org/10.1002/bdrb.21175] [PMID: 27074409]
[23]
Singh KP, Gupta K. Teratogenic effects of third-generation antiepileptic drug, pregabalin: an in vivo study. Curr Drug Saf 2018; 13(2): 113-21.
[http://dx.doi.org/10.2174/1574886313666180402145645] [PMID: 29607783]
[24]
Schneider T, Labuz D, Przewłocki R. Nociceptive changes in rats after prenatal exposure to valproic acid. Pol J Pharmacol 2001; 53(5): 531-4.
[PMID: 11990073]
[25]
Oberlander TF, Grunau RE, Fitzgerald C, Papsdorf M, Rurak D, Riggs W. Pain reactivity in 2-month-old infants after prenatal and postnatal serotonin reuptake inhibitor medication exposure. Pediatrics 2005; 115(2): 411-25.
[http://dx.doi.org/10.1542/peds.2004-0420] [PMID: 15687451]
[26]
Knaepen L, Rayen I, Charlier TD, et al. Developmental fluoxetine exposure normalizes the long-term effects of maternal stress on post-operative pain in Sprague-Dawley rat offspring. PLoS One 2013; 8(2)e57608
[http://dx.doi.org/10.1371/journal.pone.0057608] [PMID: 23437400]
[27]
Biglarnia M, Karami M, Hafshejani ZK. Differences in morphine-induced antinociception in male and female offspring born of morphine exposed mothers. Indian J Pharmacol 2013; 45(3): 227-31.
[http://dx.doi.org/10.4103/0253-7613.111904] [PMID: 23833363]
[28]
Berkley KJ. Sex differences in pain. Behav Brain Sci 1997; 20(3): 371-80.
[http://dx.doi.org/10.1017/S0140525X97221485] [PMID: 10097000]
[29]
Tonsfeldt KJ, Suchland KL, Beeson KA, Lowe JD, Li MH, Ingram SL. Sex differences in GABAA signaling in the periaqueductal gray induced by persistent inflammation. J Neurosci 2016; 36(5): 1669-81.
[http://dx.doi.org/10.1523/JNEUROSCI.1928-15.2016] [PMID: 26843648]
[30]
Toth C. Pregabalin: latest safety evidence and clinical implications for the management of neuropathic pain. Ther Adv Drug Saf 2014; 5(1): 38-56.
[http://dx.doi.org/10.1177/2042098613505614] [PMID: 25083261]
[31]
Andrade C. Safety of pregabalin in pregnancy. J Clin Psychiatry 2018; 79(5): 18f12568.
[http://dx.doi.org/10.4088/JCP.18f12568] [PMID: 30289631]
[32]
Nadebaum C, Anderson V, Vajda F, Reutens D, Wood A. Neurobehavioral consequences of prenatal antiepileptic drug exposure. Dev Neuropsychol 2012; 37(1): 1-29.
[http://dx.doi.org/10.1080/87565641.2011.589483] [PMID: 22292829]
[33]
Meador KJ, Baker G, Cohen MJ, Gaily E, Westerveld M. Cognitive/behavioral teratogenetic effects of antiepileptic drugs. Epilepsy Behav 2007; 11(3): 292-302.
[http://dx.doi.org/10.1016/j.yebeh.2007.08.009] [PMID: 17996637]
[34]
Nadebaum C, Anderson V, Vajda F, Reutens D, Barton S, Wood A. The Australian brain and cognition and antiepileptic drugs study: IQ in school-aged children exposed to sodium valproate and polytherapy. J Int Neuropsychol Soc 2011; 17(1): 133-42.
[http://dx.doi.org/10.1017/S1355617710001359] [PMID: 21092354]
[35]
Rihtman T, Parush S, Ornoy A. Developmental outcomes at preschool age after fetal exposure to valproic acid and lamotrigine: cognitive, motor, sensory and behavioral function. Reprod Toxicol 2013; 41: 115-25.
[http://dx.doi.org/10.1016/j.reprotox.2013.06.001] [PMID: 23791930]
[36]
Titze K, Koch S, Helge H, Lehmkuhl U, Rauh H, Steinhausen HC. Prenatal and family risks of children born to mothers with epilepsy: effects on cognitive development. Dev Med Child Neurol 2008; 50(2): 117-22.
[http://dx.doi.org/10.1111/j.1469-8749.2007.02020.x] [PMID: 18177411]
[37]
Melancia F, Schiavi S, Servadio M, Cartocci V, Campolongo P, Palmery M, et al. Sex-specific autistic endophenotypes induced by prenatal exposure to valproic acid involve anandamide signalling 2018; 175(18): 3699-712.
[http://dx.doi.org/10.1111/bph.14435]
[38]
Mueller BR, Bale TL. Sex-specific programming of offspring emotionality after stress early in pregnancy. J Neurosci 2008; 28(36): 9055-65.
[http://dx.doi.org/10.1523/JNEUROSCI.1424-08.2008] [PMID: 18768700]
[39]
Cohen MJ, Meador KJ, Browning N, et al. NEAD study group Fetal antiepileptic drug exposure: adaptive and emotional/behavioral functioning at age 6 years. Epilepsy Behav 2013; 29(2): 308-15.
[http://dx.doi.org/10.1016/j.yebeh.2013.08.001] [PMID: 24012508]
[40]
Estelles J, Rodríguez-Arias M, Maldonado C, Aguilar MA, Miñarro J. Prenatal cocaine exposure alters spontaneous and cocaine-induced motor and social behaviors. Neurotoxicol Teratol 2005; 27(3): 449-57.
[http://dx.doi.org/10.1016/j.ntt.2005.01.002] [PMID: 15939204]
[41]
McFadyen-Leussis MP, Lewis SP, Bond TL, Carrey N, Brown RE. Prenatal exposure to methylphenidate hydrochloride decreases anxiety and increases exploration in mice. Pharmacol Biochem Behav 2004; 77(3): 491-500.
[http://dx.doi.org/10.1016/j.pbb.2003.12.011] [PMID: 15006459]
[42]
Pauly JR, Sparks JA, Hauser KF, Pauly TH. In utero nicotine exposure causes persistent, gender-dependant changes in locomotor activity and sensitivity to nicotine in C57Bl/6 mice. Int J Dev Neurosci 2004; 22(5-6): 329-37.
[http://dx.doi.org/10.1016/j.ijdevneu.2004.05.009] [PMID: 15380832]
[43]
Coronel-Oliveros CM, Pacheco-Calderon R. Prenatal exposure to ketamine in rats: Implications on animal models of schizophrenia. Dev Psychobiol 2018; 60(1): 30-42.
[http://dx.doi.org/10.1002/dev.21586] [PMID: 29171010]
[44]
Christensen HD, Gonzalez CL, Rayburn WF. Chronic prenatal exposure to phenobarbital and long-term behavior effects on mice offspring. J Matern Fetal Neonatal Med 2004; 15(6): 351-5.
[http://dx.doi.org/10.1080/14767050410001683142] [PMID: 15280103]
[45]
Olivier JD, Vallès A, van Heesch F, et al. Fluoxetine administration to pregnant rats increases anxiety-related behavior in the offspring. Psychopharmacology (Berl) 2011; 217(3): 419-32.
[http://dx.doi.org/10.1007/s00213-011-2299-z] [PMID: 21487650]
[46]
Levav T, Saar T, Berkovich L, Golan H. Perinatal exposure to GABA-transaminase inhibitor impaired psychomotor function in the developing and adult mouse. Int J Dev Neurosci 2004; 22(3): 137-47.
[http://dx.doi.org/10.1016/j.ijdevneu.2004.03.004] [PMID: 15140467]
[47]
Main SL, Kulesza RJ. Repeated prenatal exposure to valproic acid results in cerebellar hypoplasia and ataxia Neuroscience 2017; 340: 34-47.
[http://dx.doi.org/10.1016/j.neuroscience.2016.10.052] [PMID: 27984183]