[en] Early life events can significantly alter the development of the nociceptive circuit. In fact, clinical work has shown that maternal adversity, in the form of depression, and concomitant selective serotonin reuptake inhibitor (SSRI) treatment influence nociception in infants. The combined effects of maternal adversity and SSRI exposure on offspring nociception may be due to their effects on the developing hypothalamic-pituitary-adrenal (HPA) system. Therefore, the present study investigated long-term effects of maternal adversity and/or SSRI medication use on nociception of adult Sprague-Dawley rat offspring, taking into account involvement of the HPA system. Dams were subject to stress during gestation and were treated with fluoxetine (2x/5 mg/kg/day) prior to parturition and throughout lactation. Four groups of adult male offspring were used: 1. Control+Vehicle, 2. Control+Fluoxetine, 3. Prenatal Stress+Vehicle, 4. Prenatal Stress+Fluoxetine. Results show that post-operative pain, measured as hypersensitivity to mechanical stimuli after hind paw incision, was decreased in adult offspring subject to prenatal stress alone and increased in offspring developmentally exposed to fluoxetine alone. Moreover, post-operative pain was normalized in prenatally stressed offspring exposed to fluoxetine. This was paralleled by a decrease in corticosteroid binding globulin (CBG) levels in prenatally stressed offspring and a normalization of serum CBG levels in prenatally stressed offspring developmentally exposed to fluoxetine. Thus, developmental fluoxetine exposure normalizes the long-term effects of maternal adversity on post-operative pain in offspring and these effects may be due, in part, to the involvement of the HPA system.
Research center :
CIRM - Centre Interdisciplinaire de Recherche sur le Médicament - ULiège
Helgeland H, Sandvik L, Mathiesen KS, Kristensen H, (2010) Childhood predictors of recurrent abdominal pain in adolescence: A 13-year population-based prospective study. J Psychosom Res 68: 359-367.
Wolff N, Darlington AS, Hunfeld J, Verhulst F, Jaddoe V, et al. (2010) Determinants of somatic complaints in 18-month-old children: the generation R study. J Pediatr Psychol 35: 306-316.
Leung BM, Kaplan BJ, (2009) Perinatal depression: prevalence, risks, and the nutrition link-a review of the literature. J Am Diet Assoc 109: 1566-1575.
Green PG, Chen X, Alvarez P, Ferrari LF, Levine JD, (2011) Early-life stress produces muscle hyperalgesia and nociceptor sensitization in the adult rat. Pain 152: 2549-2556.
Butkevich I, Mikhailenko V, Vershinina E, Semionov P, Makukhina G, et al. (2011) Maternal buspirone protects against the adverse effects of in utero stress on emotional and pain-related behaviors in offspring. Physiol Behav 102: 137-142.
O'Connor TG, Bergman K, Sarkar P, Glover V, (2012) Prenatal cortisol exposure predicts infant cortisol response to acute stress. Dev Psychobiol. Epub ahead of print.
Green MK, Rani CS, Joshi A, Soto-Pina AE, Martinez PA, et al. (2011) Prenatal stress induces long term stress vulnerability, compromising stress response systems in the brain and impairing extinction of conditioned fear after adult stress. Neuroscience 192: 438-451.
Abe H, Hidaka N, Kawagoe C, Odagiri K, Watanabe Y, et al. (2007) Prenatal psychological stress causes higher emotionality, depression-like behavior, and elevated activity in the hypothalamo-pituitary-adrenal axis. Neurosci Res 59: 145-151.
Rayen I, van den Hove DL, Prickaerts J, Steinbusch HW, Pawluski JL, (2011) Fluoxetine during development reverses the effects of prenatal stress on depressive-like behavior and hippocampal neurogenesis in adolescence. PLoS One 6: e24003.
Goodin BR, Smith MT, Quinn NB, King CD, McGuire L, (2012) Poor sleep quality and exaggerated salivary cortisol reactivity to the cold pressor task predict greater acute pain severity in a non-clinical sample. Biol Psychol. Epub ahead of print.
Benedetti M, Merino R, Kusuda R, Ravanelli MI, Cadetti F, et al. (2012) Plasma corticosterone levels in mouse models of pain. Eur J Pain 16: 803-815.
McLean SA, Williams DA, Harris RE, Kop WJ, Groner KH, et al. (2005) Momentary relationship between cortisol secretion and symptoms in patients with fibromyalgia. Arthritis Rheum 52: 3660-3669.
Cintra A, Zoli M, Rosen L, Agnati LF, Okret S, et al. (1994) Mapping and computer assisted morphometry and microdensitometry of glucocorticoid receptor immunoreactive neurons and glial cells in the rat central nervous system. Neuroscience 62: 843-897.
Fuxe K, Harfstrand A, Agnati LF, Yu ZY, Cintra A, et al. (1985) Immunocytochemical studies on the localization of glucocorticoid receptor immunoreactive nerve cells in the lower brain stem and spinal cord of the male rat using a monoclonal antibody against rat liver glucocorticoid receptor. Neurosci Lett 60: 1-6.
Cintra A, Molander C, Fuxe K, (1993) Colocalization of Fos- and glucocorticoid receptor-immunoreactivities is present only in a very restricted population of dorsal horn neurons of the rat spinal cord after nociceptive stimulation. Brain Res 632: 334-338.
Wang S, Lim G, Zeng Q, Sung B, Yang L, et al. (2005) Central glucocorticoid receptors modulate the expression and function of spinal NMDA receptors after peripheral nerve injury. J Neurosci 25: 488-495.
Oberlander TF, Warburton W, Misri S, Aghajanian J, Hertzman C, (2006) Neonatal outcomes after prenatal exposure to selective serotonin reuptake inhibitor antidepressants and maternal depression using population-based linked health data. Arch Gen Psychiatry 63: 898-906.
Ververs T, Kaasenbrood H, Visser G, Schobben F, de Jong-van den Berg L, et al. (2006) Prevalence and patterns of antidepressant drug use during pregnancy. Eur J Clin Pharmacol 62: 863-870.
Cooper WO, Willy ME, Pont SJ, Ray WA, (2007) Increasing use of antidepressants in pregnancy. Am J Obstet Gynecol 196: 544 e541-545.
Rampono J, Simmer K, Ilett KF, Hackett LP, Doherty DA, et al. (2009) Placental transfer of SSRI and SNRI antidepressants and effects on the neonate. Pharmacopsychiatry 42: 95-100.
Panchaud A, Garcia-Bournissen F, Csajka C, Kristensen JH, Taddio A, et al. (2011) Prediction of infant drug exposure through breastfeeding: population PK modeling and simulation of fluoxetine exposure. Clin Pharmacol Ther 89: 830-836.
Oberlander TF, Grunau RE, Fitzgerald C, Papsdorf M, Rurak D, et al. (2005) Pain reactivity in 2-month-old infants after prenatal and postnatal serotonin reuptake inhibitor medication exposure. Pediatrics 115: 411-425.
Andrews MH, Matthews SG, (2004) Programming of the hypothalamo-pituitary-adrenal axis: serotonergic involvement. Stress 7: 15-27.
Laplante P, Diorio J, Meaney MJ, (2002) Serotonin regulates hippocampal glucocorticoid receptor expression via a 5-HT7 receptor. Brain Res Dev Brain Res 139: 199-203.
Pawluski JL, Rayen I, Niessen NA, Kristensen S, van Donkelaar EL, et al. (2012) Developmental fluoxetine exposure differentially alters central and peripheral measures of the HPA system in adolescent male and female offspring. Neuroscience 220: 131-141.
Ward IL, Weisz J, (1984) Differential effects of maternal stress on circulating levels of corticosterone, progesterone, and testosterone in male and female rat fetuses and their mothers. Endocrinology 114: 1635-1644.
Van den Hove DL, Blanco CE, Aendekerk B, Desbonnet L, Bruschettini M, et al. (2005) Prenatal restraint stress and long-term affective consequences. Dev Neurosci 27: 313-320.
Smith JW, Seckl JR, Evans AT, Costall B, Smythe JW, (2004) Gestational stress induces post-partum depression-like behaviour and alters maternal care in rats. Psychoneuroendocrinology 29: 227-244.
O'Mahony SM, Myint AM, van den Hove D, Desbonnet L, Steinbusch H, et al. (2006) Gestational stress leads to depressive-like behavioural and immunological changes in the rat. Neuroimmunomodulation 13: 82-88.
Powers BE, Widholm JJ, Lasky RE, Schantz SL, (2006) Auditory deficits in rats exposed to an environmental PCB mixture during development. Toxicol Sci 89: 415-422.
Pohland RC, Byrd TK, Hamilton M, Koons JR, (1989) Placental transfer and fetal distribution of fluoxetine in the rat. Toxicol Appl Pharmacol 98: 198-205.
Romijn HJ, Hofman MA, Gramsbergen A, (1991) At what age is the developing cerebral cortex of the rat comparable to that of the full-term newborn human baby? Early Hum Dev 26: 61-67.
Houbart V, Servais AC, Charlier TD, Pawluski JL, Abts F, et al. (2012) A validated microfluidics-based LC-chip-MS/MS method for the quantitation of fluoxetine and norfluoxetine in rat serum. Electrophoresis 33: 3370-3379.
Pawluski JL, Charlier TD, Fillet M, Houbart V, Crispin HT, et al. (2012) Chronic fluoxetine treatment and maternal adversity differentially alter neurobehavioral outcomes in the rat dam. Behav Brain Res 228: 159-168.
Ren K, Anseloni V, Zou SP, Wade EB, Novikova SI, et al. (2004) Characterization of basal and re-inflammation-associated long-term alteration in pain responsivity following short-lasting neonatal local inflammatory insult. Pain 110: 588-596.
Brennan TJ, Vandermeulen EP, Gebhart GF, (1996) Characterization of a rat model of incisional pain. Pain 64: 493-501.
Knaepen L, Patijn J, van Kleef M, Mulder M, Tibboel D, et al. (2013) Neonatal repetitive needle pricking: Plasticity of the spinal nociceptive circuit and extended postoperative pain in later life. Dev Neurobiol 73: 85-97.
Hammond GL, Lahteenmaki PL, (1983) A versatile method for the determination of serum cortisol binding globulin and sex hormone binding globulin binding capacities. Clin Chim Acta 132: 101-110.
Pawluski JL, Charlier TD, Lieblich SE, Hammond GL, Galea LA, (2009) Reproductive experience alters corticosterone and CBG levels in the rat dam. Physiol Behav 96: 108-114.
Grunau RE, Tu MT, Whitfield MF, Oberlander TF, Weinberg J, et al. (2010) Cortisol, behavior, and heart rate reactivity to immunization pain at 4 months corrected age in infants born very preterm. Clin J Pain 26: 698-704.
Brummelte S, Grunau RE, Zaidman-Zait A, Weinberg J, Nordstokke D, et al. (2011) Cortisol levels in relation to maternal interaction and child internalizing behavior in preterm and full-term children at 18 months corrected age. Dev Psychobiol 53: 184-195.
Butkevich IP, Barr GA, Vershinina EA, (2007) Sex differences in formalin-induced pain in prenatally stressed infant rats. Eur J Pain 11: 888-894.
Hamalainen MM, Subieta A, Arpey C, Brennan TJ, (2009) Differential effect of capsaicin treatment on pain-related behaviors after plantar incision. J Pain 10: 637-645.
Barden N, Reul JM, Holsboer F, (1995) Do antidepressants stabilize mood through actions on the hypothalamic-pituitary-adrenocortical system? Trends Neurosci 18: 6-11.
Berguer R, Dalton M, Ferrick D, (1998) Adrenocortical response and regional T-lymphocyte activation patterns following minimally invasive surgery in a rat model. Surg Endosc 12: 236-240.
Motamed S, Klubien K, Edwardes M, Mazza L, Carli F, (1998) Metabolic changes during recovery in normothermic versus hypothermic patients undergoing surgery and receiving general anesthesia and epidural local anesthetic agents. Anesthesiology 88: 1211-1218.
Kotani N, Hashimoto H, Sato Y, Sessler DI, Yoshioka H, et al. (2001) Preoperative intradermal acupuncture reduces postoperative pain, nausea and vomiting, analgesic requirement, and sympathoadrenal responses. Anesthesiology 95: 349-356.
Moloney RD, O'Leary OF, Felice D, Bettler B, Dinan TG, et al. (2012) Early-life stress induces visceral hypersensitivity in mice. Neurosci Lett 512: 99-102.
Tsang SW, Zhao M, Wu J, Sung JJ, Bian ZX, (2011) Nerve growth factor-mediated neuronal plasticity in spinal cord contributes to neonatal maternal separation-induced visceral hypersensitivity in rats. Eur J Pain. Epub ahead of print.
Lisboa SF, Oliveira PE, Costa LC, Venancio EJ, Moreira EG, (2007) Behavioral evaluation of male and female mice pups exposed to fluoxetine during pregnancy and lactation. Pharmacology 80: 49-56.
Lee LJ, (2009) Neonatal fluoxetine exposure affects the neuronal structure in the somatosensory cortex and somatosensory-related behaviors in adolescent rats. Neurotox Res 15: 212-223.