Neonatal maternal separation alters stress-induced responses to viscerosomatic nociceptive stimuli in rat
S. V. COUTINHO,1 P. M. PLOTSKY,4 M. SABLAD,1 J. C. MILLER,1 H. ZHOU,1 A. I BAYATI,5 J. A. MCROBERTS,1 AND E. A. MAYER1,2,3
1 UCLA/CURE Neuroenteric Disease Program and Brain Research Institute, Departments of Medicine,
2 Physiology, and 3 Biobehavioral Sciences, University of California at Los Angeles School of Medicine, Los Angeles, California 90095;
4 Stress Neurobiology Laboratory, Emory University School of Medicine, Atlanta, Georgia 30322; and
5 AstraZeneca R&D, 5431 83 Mo¨lndal, Sweden Received 7 June 2001; accepted in final form 2 October 2001
Coutinho, S. V., P. M. Plotsky, M. Sablad, J. C. Miller, H. Zhou, A. I. Bayati, J. A. McRoberts, and E. A. Mayer. Neonatal maternal separation alters stress-induced responses to viscerosomatic nociceptive stimuli in rat. Am J Physiol Gastrointest Liver Physiol 282: G307–G316, 2002. First published October 3, 2001; 10.1152/ajpgi.00240.2001.— This study investigated the combined effect of neonatal maternal separation and acute psychological stress on pain responses in adult rats. Long-Evans dams and their male pups were reared under two conditions: 1) 180 min daily maternal separation (MS180) on postnatal days 2–14 or 2) no handling or separation (NH). At 2 mo of age, visceromotor responses to graded intensities of phasic colorectal distension (10–80 mmHg) at baseline as well as following acute 60 min water avoidance stress (WA) were significantly higher in MS180 rats. Both groups showed similar stress-induced visceral hyperalgesia in the presence of naloxone (20 mg/kg ip). MS180 rats had smaller stress-induced cutaneous analgesia in the tail-flick test compared with NH rats, with a residual naloxone-resistant component. MS180 rats showed an enhanced fecal pellet output following WA or exposure to a novel environment. These data suggest that early life events predispose adult Long-Evans rats to develop visceral hyperalgesia, reduced somatic analgesia, and increased colonic motility in response to an acute psychological stressor, mimicking the cardinal features of irritable bowel syndrome.