Environmental enrichment prevents chronic stress-induced brain-gut axis dysfunction through a GR-mediated mechanism in the central nucleus of the amygdala
Albert Orock
Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
Search for more papers by this authorTijs Louwies
Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
Search for more papers by this authorTian Yuan
Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
Search for more papers by this authorCorresponding Author
Beverley Greenwood-Van Meerveld
Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
Department of Veterans Affairs Health Care System, Oklahoma City, Oklahoma
Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
Correspondence
Beverley Greenwood-Van Meerveld, Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, O'Donoghue Building, Room 332, 1122 NE 13th Street, Oklahoma City, OK 73117.
Email: [email protected]
Search for more papers by this authorAlbert Orock
Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
Search for more papers by this authorTijs Louwies
Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
Search for more papers by this authorTian Yuan
Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
Search for more papers by this authorCorresponding Author
Beverley Greenwood-Van Meerveld
Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
Department of Veterans Affairs Health Care System, Oklahoma City, Oklahoma
Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
Correspondence
Beverley Greenwood-Van Meerveld, Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, O'Donoghue Building, Room 332, 1122 NE 13th Street, Oklahoma City, OK 73117.
Email: [email protected]
Search for more papers by this authorAbstract
Background
Cognitive behavioral therapy (CBT) improves quality of life of patients with irritable bowel syndrome (IBS), a disorder characterized by chronic visceral pain and abnormal bowel habits. Whether CBT can actually improve visceral pain in IBS patients is still unknown. The aim of this study is to evaluate whether environment enrichment (EE), the animal analog of CBT, can prevent stress-induced viscero-somatic hypersensitivity through changes in glucocorticoid receptor (GR) signaling within the central nucleus of the amygdala (CeA).
Methods
Rats were housed in either standard housing (SH) or EE for 7 days before and during daily water avoidance stress (WAS) exposure (1-h/d for 7 days). In the first cohort, visceral and somatic sensitivity were assessed via visceromotor response to colorectal distention and von Frey Anesthesiometer 24 hous and 21 days after WAS. In another cohort, the CeA was isolated for GR mRNA quantification.
Key Results
Environment enrichment for 7 days before and during the 7 days of WAS persistently attenuated visceral and somatic hypersensitivity when compared to rats placed in SH. Environment enrichment exposure also prevented the WAS-induced decrease in GR expression in the CeA.
Conclusion & Inferences
Pre-exposure to short-term EE prevents the stress-induced downregulation of GR, and inhibits visceral and somatic hypersensitivity induced by chronic stress. These results suggest that a positive environment can ameliorate stress-induced pathology and provide a non-pharmacological therapeutic option for disorders such as IBS.
CONFLICT OF INTEREST
None of the authors have any conflicts of interest.
REFERENCES
- 1Hofmann SG, Wu JQ, Boettcher H. Effect of cognitive-behavioral therapy for anxiety disorders on quality of life: a meta-analysis. J Consult Clin Psychol. 2014; 82(3): 375-391.
- 2Hans E, Hiller W. A meta-analysis of nonrandomized effectiveness studies on outpatient cognitive behavioral therapy for adult anxiety disorders. Clin Psychol Rev. 2013; 33(8): 954-964.
- 3Chambless DL, Ollendick TH. Empirically supported psychological interventions: controversies and evidence. Annu Rev Psychol. 2001; 52: 685-716.
- 4Castro MM, Daltro C, Kraychete DC, Lopes J. The cognitive behavioral therapy causes an improvement in quality of life in patients with chronic musculoskeletal pain. Arq Neuropsiquiatr. 2012; 70(11): 864-868.
- 5Crofford LJ. Psychological aspects of chronic musculoskeletal pain. Best Pract Res Clin Rheumatol. 2015; 29(1): 147-155.
- 6Bernardy K, Füber N, Köllner V, Häuser W. Efficacy of cognitive-behavioral therapies in fibromyalgia syndrome – a systematic review and metaanalysis of randomized controlled trials. J Rheumatol. 2010; 37(10): 1991-2005.
- 7Haugstad GK, Haugstad TS, Kirste UM, et al. Continuing improvement of chronic pelvic pain in women after short-term Mensendieck somatocognitive therapy: results of a 1-year follow-up study. Am J Obstet Gynecol. 2008; 199(6): 615.e1-615.e8.
- 8Ismail A, Moore C, Alshishani N, Yaseen K, Alshehri MA. Cognitive behavioural therapy and pain coping skills training for osteoarthritis knee pain management: a systematic review. J Phys Ther Sci. 2017; 29(12): 2228-2235.
- 9Lackner JM, Jaccard J, Keefer L, et al. Improvement in gastrointestinal symptoms after cognitive behavior therapy for refractory irritable bowel syndrome. Gastroenterology. 2018; 155(1): 47-57.
- 10Peery AF, Dellon ES, Lund J, et al. Burden of gastrointestinal disease in the United States: 2012 update. Gastroenterology. 2012; 143(5): 1179-1187.e3.
- 11Tuteka A, Tolman KG, Talley NJ, et al. Bowel disorders in Gulf War Veterans. Gastroenterology. 2008; 134(4, Suppl 1): A-31. p 182. https://www.gastrojournal.org/article/S0016-5085(08)60152-3/abstract
- 12Lovell RM, Ford AC. Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis. Clin Gastroenterol Hepatol. 2012; 10(7): 712-721.e4.
- 13Dunphy RC, Bridgewater L, Price DD, Robinson ME, Zeilman CJ, Verne NG. Visceral and cutaneous hypersensitivity in Persian Gulf war veterans with chronic gastrointestinal symptoms. Pain. 2003; 102(1–2): 79-85.
- 14Riedl A, Schmidtmann M, Stengel A, et al. Somatic comorbidities of irritable bowel syndrome: a systematic analysis. J Psychosom Res. 2008; 64(6): 573-582.
- 15Popa S-L, Dumitrascu DL. Anxiety and IBS revisited: ten years later. Clujul Med. 2015: 88(3): 253-257.
- 16Banerjee A, Sarkhel S, Sarkar R, Dhali GK. Anxiety and depression in irritable bowel syndrome. Indian J Psychol Med. 2017; 39(6): 741-745.
- 17Bonaz B, Baciu M, Papillon E, et al. Central processing of rectal pain in patients with irritable bowel syndrome: an fMRI study. Am J Gastroenterol. 2002; 97(3): 654-661.
- 18Naliboff BD, Berman S, Chang L, et al. Sex-related differences in IBS patients: central processing of visceral stimuli. Gastroenterology. 2003; 124(7): 1738-1747.
- 19Chang L, Sundaresh S, Elliott J, et al. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in irritable bowel syndrome. Neurogastroenterol Motil. 2009; 21(2): 149-159.
- 20Myers B, Greenwood-Van Meerveld B. Differential involvement of amygdala corticosteroid receptors in visceral hyperalgesia following acute or repeated stress. Am J Physiol Gastrointest Liver Physiol. 2012; 302(2): G260-G266.
- 21Myers B, McKlveen JM, Herman JP. Neural regulation of the stress response: the many faces of feedback. Cell Mol Neurobiol. 2012; 32(5): 683-694.
- 22Beaulieu S, DiPaolo T, Côté J, Barden N. Participation of the central amygdaloid nucleus in the response of adrenocorticotropin secretion to immobilization stress: opposing roles of the noradrenergic and dopaminergic systems. Neuroendocrinology. 1987; 45(1): 37-46.
- 23Myers B, Dittmeyer K, Greenwood-Van Meerveld B. Involvement of amygdaloid corticosterone in altered visceral and somatic sensation. Behav Brain Res. 2007; 181(1): 163-167.
- 24Johnson AC, Greenwood-Van Meerveld B. Knockdown of steroid receptors in the central nucleus of the amygdala induces heightened pain behaviors in the rat. Neuropharmacology. 2015; 93: 116-123.
- 25Baumans V, Van Loo PL. How to improve housing conditions of laboratory animals: the possibilities of environmental refinement. Vet J. 2013; 195(1): 24-32.
- 26Simpson J, Kelly JP. The impact of environmental enrichment in laboratory rats – behavioural and neurochemical aspects. Behav Brain Res. 2011; 222(1): 246-264.
- 27Bennett JC, Mcrae P, Levy L, Frick K. Long-term continuous, but not daily, environmental enrichment reduces spatial memory decline in aged male mice. Neurobiol Learn Mem. 2006; 85(2): 139-152.
- 28Harburger LL, Lambert TJ, Frick KM. Age-dependent effects of environmental enrichment on spatial reference memory in male mice. Behav Brain Res. 2007; 185(1): 43-48.
- 29Sampedro-Piquero P, Begega A. Environmental enrichment as a positive behavioral intervention across the lifespan. Curr Neuropharmacol. 2017; 15(4): 459-470.
- 30Gabriel AF, Paoletti G, Seta DD, et al. Enriched environment and the recovery from inflammatory pain: social versus physical aspects and their interaction. Behav Brain Res. 2010; 208(1): 90-95.
- 31Vachon P, Millecamps M, Low L, et al. Alleviation of chronic neuropathic pain by environmental enrichment in mice well after the establishment of chronic pain. Behav Brain Funct. 2013; 9: 22.
- 32Tai LW, Yeung SC, Cheung CW. Enriched environment and effects on neuropathic pain: experimental findings and mechanisms. Pain Pract. 2018; 18(8): 1068-1082.
- 33Lehmann ML, Herkenham M. Environmental enrichment confers stress resiliency to social defeat through an infralimbic cortex-dependent neuroanatomical pathway. J Neurosci. 2011; 31(16): 6159-6173.
- 34Myers B, Greenwood-Van Meerveld B. Corticosteroid receptor-mediated mechanisms in the amygdala regulate anxiety and colonic sensitivity. Am J Physiol Gastrointest Liver Physiol. 2007; 292(6): G1622-G1629.
- 35Prusator DK, Greenwood-Van Meerveld B. Sex-related differences in pain behaviors following three early life stress paradigms. Biol Sex Differ. 2016; 7: 29-29.
- 36Parent-Vachon M, Vachon P Environmental enrichment alleviates chronic pain in rats following a spared nerve injury to induce neuropathic pain. A preliminary study. Vet Med (Auckl). 2018; 9: 69-72.
- 37Beehler GP, Murphy JL, King PR, et al. Brief cognitive behavioral therapy for chronic pain: results from a clinical demonstration project in primary care behavioral health. Clin J Pain. 2019; 35(10): 809-817.
- 38Morano R, Hoskins O, Smith BL, Herman JP. Loss of environmental enrichment elicits behavioral and physiological dysregulation in female rats. Front Behav Neurosci. 2019; 12: 287-287.
- 39Smith BL, Lyons CE, Correa FG, et al. Behavioral and physiological consequences of enrichment loss in rats. Psychoneuroendocrinology. 2017; 77: 37-46.
- 40Besheer J, Fisher KR, Grondin JJM, Cannady R, Hodge CW. The effects of repeated corticosterone exposure on the interoceptive effects of alcohol in rats. Psychopharmacology. 2012; 220(4): 809-822.
- 41McEwen BS. Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol Rev. 2007; 87(3): 873-904.
- 42Meerveld BG-V, Johnson AC. Mechanisms of stress-induced visceral pain. J Neurogastroenterol Motil. 2018; 24(1): 7-18.
- 43Tran L, Sawalha AH, Greenwood Van-Meerveld B. Importance of epigenetic mechanisms in visceral pain induced by chronic water avoidance stress. Psychoneuroendocrinology. 2013; 38(6): 898-906.
- 44Greenwood-Van Meerveld B, Gibson M, Gunter W, Shepard J, Foreman R, Myers D. Stereotaxic delivery of corticosterone to the amygdala modulates colonic sensitivity in rats. Brain Res. 2001; 893(1–2): 135-142.
- 45Arnett MG, Pan MS, Doak W, Cyr PEP, Muglia LM, Muglia LJ. The role of glucocorticoid receptor-dependent activity in the amygdala central nucleus and reversibility of early-life stress programmed behavior. Transl Psychiat. 2015; 5(4): e542.
- 46Kolber BJ, Roberts MS, Howell MP, Wozniak DF, Sands MS, Muglia LJ. Central amygdala glucocorticoid receptor action promotes fear-associated CRH activation and conditioning. Proc Natl Acad Sci USA. 2008; 105(33): 12004-12009.
- 47Novaes LS, dos Santos NB, Batalhote RFP, et al. Environmental enrichment protects against stress-induced anxiety: role of glucocorticoid receptor, ERK, and CREB signaling in the basolateral amygdala. Neuropharmacology. 2017; 113(Pt A): 457-466.
- 48Reichmann F, Painsipp E, Holzer P. Environmental enrichment and gut inflammation modify stress-induced c-Fos expression in the mouse corticolimbic system. PLoS ONE. 2013; 8(1):e54811.