Comorbidity between somatic symptom disorder and dissociative amnesia is best explained by trauma-amnesia-pain theory
Dissociative amnesia is comorbid with somatic symptom disorder (SSD), yet this link is not well-understood. Clinical studies indicate that childhood trauma, especially sexual abuse and emotional abuse, are primary causal factors in the etiology of SSD. This paper provides evidence that dissociative amnesia is an explanatory variable between childhood trauma and SSD. As many or more trauma victims develop amnesia and somatic complaints as those who develop post-traumatic stress disorder (PTSD), but SSD and dissociative amnesia receive much less attention. This leaves clinicians and patients without effective intervention and sometimes causes misdiagnosis. PTSD’s neuroendocrinological cascade, from peritraumatic perception to psychobehavioral endpoints is well-mapped, and it informs an opponent-process for dissociative amnesia and SSD, allowing a better conceptualization of a primary cause of SSD – trauma. The novel trauma-amnesia-pain (T-A-P) neuroendocrinological map presented here is a mirror process of the tonic immobility-PTSD pathway initiated by the hypothalamus-pituitary-adrenal (HPA) axis. Dissociative amnesia-SSD develops through the same HPA axis pathway, with PTSD essentially being a downregulated cortisol response and T-A-P an upregulated cortisol response. Copious evidence has now emerged from neurological, physiological, and clinical studies of animals and people regarding the role controllable stress/trauma plays in the etiology of both amnesia and analgesia. T-A-P also validates the decision to consolidate pain disorder, somatization disorder, and functional somatic disorder under one nosological category in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision. The implications of this theory are important for both prevention and effective intervention with trauma-induced SSD.
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Publishing; 2022. doi: 10.1176/appi.books.9780890425787
- Eilers H, Aan Het Rot M, Jeronimus BF. Childhood trauma and adult somatic symptoms. Psychosom Med. 2023;85:408-416. doi: 10.1097/PSY.0000000000001208
- Löwe B, Toussaint A, Rosmalen JG, et al. Persistent physical symptoms: Definition, genesis, and management. Lancet. 2024;403(10444):2649-2662. doi: 10.1016/S0140-6736(24)00623-8
- Fink P, Schröder A. One single diagnosis, bodily distress syndrome, succeeded to capture 10 diagnostic categories of functional somatic syndromes and somatoform disorders. J Psychosom Res. 2011;68(5):415-426. doi: 10.1016/j.jpsychores.2010.02.004
- Hiller W, Heuser J, Fichter MM. The DSM-IV nosology of chronic pain: A comparison of pain disorder and multiple somatization syndrome. Eur J Pain. 2000;4:45-55. doi: 10.1053/eujp.1999.0155
- Kanaan RAA, Lepine JP, Wessely SC. The association or otherwise of the functional somatic syndromes. Psychosom Med. 2007;69:855-859. doi: 10.1097/PSY.0b013e31815b001a
- van der Kolk BA. The Body Keeps the Score: Brain, Mind, and Body in the Healing of Trauma. New York: Penguin Books; 2014.
- Bovin MJ, Marx B. The importance of the peritraumatic experience in defining traumatic stress. Psychol Bull. 2011;137(1):47-67. doi: 10.1037/a0021353
- Foa EB, Zinbarg R, Rothbaum BO. Uncontrollability and unpredictability in post-traumatic stress disorder: An animal model. Psychol Bull. 1992;112:218-238. doi: 10.1037/0033-2909.112.2.218
- Olff M, Langeland W, Gersons BPR. Effects of appraisal and coping on the neuroendocrine response to extreme stress. Neurosci Biobehav Rev. 2005;29:457-467. doi: 10.1016/j.neubiorev.2004.12.006
- Mayer EA, Bushnell MC. Synthesis. In: Mayer EA, Bushnell MC, editors. Functional Pain Syndromes: Presentation and Pathophysiology. Washington DC: IASPPress; 2009. p. 531-565.
- McNally RJ. The science and folklore of traumatic amnesia. Clin Psychol Sci Pract. 2004;11(1):29-33. doi: 10.1093/clipsy.bph056
- Bremner JD, Marmar CR, editors. Trauma, Memory, and Dissociation. Washington, DC: American Psychiatric Press; 1998.
- Brewin CR. Autobiographical memory for trauma: Update on four controversies. Memory. 2007;15(3):227-248. doi: 10.1080/09658210701256423
- Joseph R. Traumatic amnesia, repression, and hippocampus injury due to emotional stress, corticosteroids and enkephalins. Child Psychiatry Hum Dev. 1998;29(2):169-185. doi: 10.1023/A:1025092117657
- Gaensbauer TJ. Representations of trauma in infancy: Clinical and theoretical implications for the understanding of early memory. Infant Ment Health J. 2002;23(3):259-277. doi: 10.1002/imhj.10020
- Gazzaniga MS, Ivry RB, Mangun GR. Cognitive Neuroscience: The Biology of the Mind. New York: Norton; 2002.
- Jacobs WJ, Nadel L. Neurobiology of reconstructed memory. Psychol Public Policy Law. 1998;4(4):1110-1134. doi: 10.1037/1076-8971.4.4.1110
- Mancia M. Implicit memory and unrepressed unconscious. In: Mancia M, editor. Psychoanalysis and Neuroscience. Milan, Italy: Springer; 2006. p. 97-123.
- Nissen MJ, Knopman DS, Schacter DL. Neurochemical dissociation of memory systems. Neurology. 1987;37:789-794. doi: 10.1212/WNL.37.5.789
- Tulving E. Multiple memory systems and consciousness. Hum Neurobiol. 1987;5:57-80.
- Alexander KW, Quas JA, Goodman GS, et al. Traumatic impact predicts long-term memory for documented child sexual abuse. Psychol Sci. 2005;16:33-40. doi: 10.1111/j.0956-7976.2005.00777.x
- Bremner JD. The neurobiology of trauma and memory in children. In: Howe ML, Goodman GS, Cichetti D, editors. Stress, Trauma, and Children’s Memory Development: Neurobiological, Cognitive, Clinical, and Legal Perspectives. New York: Oxford University Press; 2008. p. 11-49.
- Brewerton TD, Dansky BS, Kilpatrick DG, O’Neil PM. Bulimia nervosa, PTSD, and forgetting: Results from the national women’s study. In: Williams LM, Banyard VL, editors. Trauma and Memory. Thousand Oaks, CA: Sage Publications; 1999. p. 127-138.
- Delahanty DL, Glover D, Golier J. Neurobiology of memory and dissociation in trauma survivors. Ann N Y Acad Sci. 2004;1032:183-185. doi: 10.1196/annals.1314.016
- Goodman GS, Ghetti S, Quas JA, et al. A prospective study of memory for child sexual abuse: New findings relevant to the repressed-memory controversy. Psychol Sci. 2003;14:113-118. doi: 10.1111/1467-9280.01428
- Widom CS, Morris S. Accuracy of adult recollections of childhood victimization, Part 2: Childhood sexual abuse. Psychol Assess. 1997;9:34-46. doi: 10.1037/1040-3590.9.1.34
- Williams LM. Recall of childhood trauma: A prospective study of women’s memories of child sexual abuse. J Consult Clin Psychol. 1994;62:1167-1176. doi: 10.1037/0022-006X.62.6.1167
- Alpert JL, Brown LS, Courtois CA. Symptomatic clients and memories of childhood abuse: What the trauma and child sexual abuse literature tells us. Psychol Public Policy Law. 1998;4(4):941-995. doi: 10.1037/1076-8971.4.4.941
- Fredrickson R. Repressed Memories: A Journey of Recovery from Sexual Abuse. New York: Simon and Schuster; 1992.
- Breslau N, Kessler RC, Chilcoat HD, Schultz LR, Davis GC, Andreski P. Trauma and posttraumatic stress disorder in the community: The 1996 Detroit area survey of trauma. Arch Gen Psychiatry. 1998;55(7):626-632. doi: 10.1001/archpsyc.55.7.626
- Freyd JJ. Betrayal Trauma: The Logic of Forgetting Childhood Abuse. Cambridge, MA: Harvard University Press; 1997.
- Herman JL. Trauma and Recovery. New York: Basic Books; 1992.
- Lima AA, Fiszman A, Marques-Portella C, et al. The impact of tonic immobility reaction on the prognosis of posttraumatic stress disorder. J Psychiatr Res. 2010;44(4):224-228. doi: 10.1016/j.jpsychires.2009.08.005
- Rocha-Rego V, Fiszman A, Portugal LC, et al. Is tonic immobility the core sign among conventional peritraumatic signs and symptoms listed for PTSD? J Affect Disord. 2009;115:269-273. doi: 10.1016/j.jad.2008.09.005
- Bovin MJ, Jager-Hyman S, Gold SD, Marx BP, Sloan DM. Tonic immobility mediates the influence of peritraumatic fear and perceived inescapability on posttraumatic stress symptom severity among sexual assault survivors. J Trauma Stress. 2008;21:402-409. doi: 10.1002/jts.20354
- Hagenaars MA, Putman P. Attentional control affects the relationship between tonic immobility and intrusive memories. J Behav Ther Exp Psychiatry. 2011;42:379-383. doi: 10.1016/j.jbtep.2011.02.013
- Marx BP, Forsyth JP, Gallup GG, Fuse T, Lexington JM. Tonic immobility as an evolved predator defense: Implications for sexual assault survivors. Clin Psychol Sci Pract. 2008;15:74-90. doi: 10.1111/j.1468-2850.2008.00112
- Volchan E, Souza GG, Franklin CM, et al. Is there tonic immobility in humans? Biological evidence from victims of traumatic stress. Biol Psychol. 2011;88:13-19. doi: 10.1016/j.biopsycho.2011.06.002
- Van der Kolk BA, Greenberg MS, Orr SE, Pitman RK. Endogenous opioids, stress induced analgesia, and posttraumatic stress disorder. Psychopharmacol Bull. 1989;25:417-422.
- Nijenhuis ER, Spinhoven P, van Dyck R, van der Hart O, Vanderlinden J. Degree of somatoform and psychological dissociation in dissociative disorder is correlated with reported trauma. J Trauma Stress. 1998;11:711-730. doi: 10.1023/A:1024493332751
- Sijbrandij M, Engelhard IM, Opmeer BC, et al. The structure of peritraumatic dissociation: A cross validation in clinical and nonclinical samples. J Trauma Stress. 2012;25(4):475-479. doi: 10.1002/jts.21716
- Werner KB, Griffin MG. Peritraumatic and persistent dissociation as predictors of PTSD symptoms in a female cohort. J Trauma Stress. 2012;25:401-407. doi: 10.1002/jts.21725
- Delahanty DL, Royer DK, Raimonde AJ, Spoonster E. Peritraumatic dissociation is inversely related to catecholamine levels in initial urine samples of motor vehicle accident victims. J Trauma Dissociation. 2003;4(1):65-80. doi: 10.1300/J229v04n01_05
- Mobbs D, Marchant JL, Hassabis D, et al. From threat to fear: The neural organization of defensive fear systems in humans. J Neurosci. 2009;29(39):12236-12243. doi: 10.1523/jneurosci.2378-09.2009
- Drugan RC. Coping with traumatic stress interferes with memory for the event. In: Williams LM, Banyard VL, editors. Trauma and Memory. Thousand Oaks, CA: Sage Publications; 1999. p. 245-256.
- Janig W. Autonomic nervous system dysfunction. In: Mayer EA, Bushnell MC, editorss. Functional Pain Syndromes: Presentation and Pathophysiology. Seattle, WA: IASP Press; 2009. p. 265-300.
- Navalta CP, Tomoda A, Teicher MH. Trajectories of neurobehavioral development: The clinical neuroscience of child abuse. In: Howe MLG, Cichetti D, editors. Stress, Trauma, and Children’s Memory Development: Neurobiological, Cognitive, Clinical, and Legal Perspectives. Oxford: Oxford University Press; 2008. p. 50-82.
- Schacter DL, Koutstaal W, Norman KA. Can cognitive neuroscience illuminate the nature of traumatic childhood memories? In: Williams LM, Banyard VL, editors. Trauma and Memory. United States: Sage Publications; 1999. p. 257-269.
- Delahanty DL, Herberman HB, Craig KJ, et al. Acute and chronic distress and posstraumatic stress disorder as a function of responsibility for serious motor vehicle accidents. J Consult Clin Psychol. 1997;65(4):560-567. doi: 10.1037/0022-006x.65.4.560
- Delahanty DL, Raimonde AJ, Spoonster E. Initial posttraumatic urinary cortisol levels predict subsequent PTSD symptoms in motor vehicle accident victims. Biol Psychiatry. 2000;48:940-947. doi: 10.1016/S0006-3223(00)00896-9
- Payne JD, Jackson ED, Hoscheidt S, Ryan L, Jacobs WJ, Nadel L. Stress administered prior to encoding impairs neutral but enhances emotional long-term episodic memories. Learn Mem. 2007;14:861-868. doi: 10.1101/lm.743507
- Cianciulli C. Declarative Memory, Cortisol Reactivity, and Psychological Symptoms in Chronically Abused Girls. Dissertation. United States: University of Massachusetts- Amherst; 2000.
- McEwen BS. Plasticity of the hippocampus: Adaptation to chronic stress and allostatic load. Ann N Y Acad Sci. 2001;933:265-277. doi: 10.1111/j.1749-6632.2001.tb05830
- O’Donnell TM. CRH and AVP in Depressed Women with and Without Histories of Interpersonal Trauma. Dissertation. Canada: University of Alberta-Edmonton; 2009.
- Schelling G. Effects of stress hormones on traumatic memory formation and the development of posttraumatic stress disorder in critically ill patients. Neurobiol Learn Mem. 2002;78(3):596-609. doi: 10.1006/nlme.2002.4083
- Schelling G, Roozendaal B, de Quervain DJF. Can posttraumatic stress disorder be prevented with glucocorticoids? Ann N Y Acad Sci. 2004;1032:158-166. doi: 10.1196/annals.1314.013
- Soravia LM, de Quervain DJ, Heinrichs M. Glucocorticoids do not reduce subjective fear in healthy subjects exposed to social stress. Biol Psychol. 2009;81(3):184-188. doi: 10.1016/j.biopsycho.2009.04.001
- Alexander JK, DeVries AC, Kigerl KA, Dahlman JM, Popovich PG. Stress exacerbates neuropathic pain via glucocorticoid and NMDA receptor activation. Brain Behav Immun. 2009;23(6):851-860. doi: 10.1016/j.bbi.2009.04.001
- Wahbeh H, Oken BS. Salivary cortisol lower in posttraumatic stress disorder. J Trauma Stress. 2013;26(2):241-248. doi: 10.1002/jts.21798
- Zohar J, Yahalom H, Kozlovsky N, et al. High dose hydrocortisone immediately after trauma may alter the trajectory of PTSD: Interplay between clinical and animal studies. Eur Neuropsychopharmacol. 2011;21(11):796-809. doi: 10.1016/j.euroneuro.2011.06.001
- Andreano JM, Cahill L. Glucocorticoid release and memory consolidation in men and women. Psychol Sci. 2006;17(6):466-470. doi: 10.1111/j.1467-9280.2006.01729.x
- Korel DL, Gold PE. Modulation of learning and memory by adrenal and ovarian hormones. In: Kesner RP, Martinez JL Jr., editors. Neurobiol Learn Mem. 2nd ed. Burlington, MA: Academic Press; 2007. p. 621.
- McCleery JM, Harvey AG. Integration of psychological and biological approaches to trauma memory: Implications for pharmacological prevention of PTSD. J Trauma Stress. 2004;17(6):485-496. doi: 10.1007/s10960-004-5797-5
- Qiu GL, Peng LJ, Wang P, et al. In vivo imaging reveals a synchronized correlation among neurotransmitter dynamics during propofol and sevoflurane anesthesia. Zool Res. 2024;45(3):679-690. doi: 10.24272/j.issn.2095-8137.2023.302
- Souza da Silva LF, Menescal-de-Oliveira L. Cholinergic modulation of tonic immobility and nociception in the NRM of guinea pig. Physiol Behav. 2006;87:821-827. doi: 10.1016/j.physbeh.2006.01.019
- Tsigos C, Chrousos GP. Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. J Psychosom Res. 2002;53(4):865-871. doi: 10.1016/S0022-3999(02)00429-4
- Girdler SS, Maixner W, Naftel HA, Stewart PW, Moretz RL, Light KC. Cigarette smoking, stress-induced analgesia and pain perception in men and women. Pain. 2005;114(3):372-385. doi: 10.1016/j.pain.2004.12.035
- Pinto-Ribeiro F, Almeida A, Pego JM, Cerqueira J, Sousa N. Chronic unpredictable stress inhibits nociception in male rats. Neurosci Lett. 2004;359:73-76. doi: 10.1016/j.neulet.2004.02.016
- Pinto-Ribeiro F, Moreira V, Pego JM, Leão P, Almeida A, Sousa N. Antinociception induced by chronic glucocorticoid treatment is correlated to local modulation of spinal neurotransmitter content. Mol Pain. 2009;5(24):41. doi: 10.1186/1744-8069-5-41
- Tak LM, Rosmalen JGM. Psychoneuroendocrinology of functional somatic disorders. In: Czerbska MT, editor. Psychoneuroendocrinology Research Trends. Waltham, MA: Nova Biomedical Books; 2007. p. 463-495.
- Uki M, Nabekura J, Akaike N. Suppression of the nicotinic acetylcholine response in rat superior cervical ganglionic neurons by steroids. J Neurochem. 1999;72(2):808-814. doi: 10.1046/j.1471-4159.1999.0720808
- Drugan RC, Ader DN, Maier SF. Shock controllability and the nature of stress-induced analgesia. Behav Neurosci. 1985;99(5):791-801. doi: 10.1037/0735-7044.99.5.791
- Leite-Panissi CRA, Rodrigues CL, Brentegani MR, Menescal-de-Oliveira L. Endogenous opiate analgesia induced by tonic immobility in guinea pigs. Braz J Med Biol Res. 2001;34:245-250. doi: 10.1590/S0100-879X2001000200013
- Drugan RC, Basile AS, Ha JH, Ferland R. The protective effects of stress control may be mediated by increased brain levels of benzodiazepine receptor agonists. Brain Res. 1994;661:127-136. doi: 10.1016/0006-8993(94)91189-4
- Drugan RC, Basile AS, Ha JH, Healy D, Ferland RJ. Analysis of the importance of controllable versus uncontrollable stress on subsequent behavioral and physiological functioning. Brain Res Brain Res Protoc. 1997;2:69-74. doi: 10.1016/S1385-299X(97)00031-7
- Bhatnagar S, Shanks N, Meaney MJ. Plaque-forming cell responses and antibody titers following injection of sheep red blood cells in nonstressed, acute, and/or chronically stressed handled and nonhandled animals. Dev Psychobiol. 1996;29:171-181. doi: 10.1002/(SICI)1098-2302(199603)29:2<171:AID-DEV 6>3.0.CO;2-P
- Valet M, Gundel H, Sprenger T, et al. Patients with pain disorder show gray-matter loss in pain-processing structures: A voxel-based morphometric study. Psychosom Med. 2009;71:49-56. doi: 10.1097/PSY.0b013e31818d1e02
- Heim C, Ehlert U, Hanker JP, Hellhammer DH. Psychological and endocrine correlates of chronic pelvic pain associated with adhesions. J Psychosom Obstet Gynecol. 1999;20(1):11-20. doi: 10.3109/01674829909075572
- Herman JP, McKlveen JM, Ghosal S, et al. Regulation of the hypothalamic-pituitary-adrenocortical stress response. Compr Physiol. 2016;6(2):603-621. doi: 10.1002/cphy.c150015
- Roozendaal B, Schelling G, McGaugh JL. Corticotropin-releasing factor in the basolateral amygdala enhances memory consolidation via an interaction with the Beta-adrenoceptor-cAMP pathway: Dependence on glucocorticoid receptor activation. J Neurosci. 2008;28(26):6642-6651. doi: 10.1523/jneurosci.1336-08.2008
- Mueller B, Figueroa A, Robinson-Papp J. Structural and functional connections between the autonomic nervous system, hypothalamic-pituitary-adrenal axis, and the immune system: A context and time dependent stress response network. Neurol Sci. 2022;43(2):951-960. doi: 10.1007/s10072-021-05810-1
- Nemeroff CB, Vale WW. The neurobiology of depression: Inroads to treatment and new drug discovery. J Clin Psychiatry. 2005;66(Suppl 7):5-13.
- Kamohara M, Matsuo A, Takasaki J, et al. Identification of MrgX2 as a human G-protein-coupled receptor for proadrenomedullin N-terminal peptides. Biochem Biophys Res Commun. 2005;330:1146-1152. doi: 10.1016/j.bbrc.2005.03.0888
- Katoh F, Kitamura K, Niina H, et al. Proadrenomedullin N-terminal 20 peptide (PAMP), an endogenous anticholinergic peptide: Its exocytotic secretion and inhibition of catecholamine secretion in adrenal medulla. J Neurochem. 1995;64:459-461. doi: 10.1046/j.1471-4159.1995.64010459.x
- Masada K, Nagayama T, Hosokawa A, et al. Effects of adrenomedullin and PAMP on adrenal catecholamine release in dogs. Am J Physiol Regul. 1999;276(4):R1118-R1124. doi: 10.1152/ajpregu.1999.276.4.R1118
- Travers S, Martinerie L, Xue QY, et al. Adrenomedullin: New inhibitory regulator for cortisol synthesis and secretion. J Endocrinol. 2021;251(1):97-109. doi: 10.1530/JOE-20-0564
- Strohle A, Holsboer F. Stress responsive neurohormones in depression and anxiety. In: Kasper S, den Loer JA, Sitsen JAM, editors. Handbook of Depression and Anxiety: A Biological Approach. United States: CRC Press; 2003. p. 207-228.
- Vinkers CH, Kuzminskaite E, Lamers F, Giltay EJ, Penninx B. An integrated approach to understand biological stress system dysregulation across depressive and anxiety disorders. J Affect Disord. 2021;283:139-146. doi: 10.1016/j.jad.2021.01.051
- Hasselmo ME, Wyble BP. Free recall and recognition in a network model of the hippocampus: Simulating effects of scopolamine on human memory function. Behav Brain Res. 1997;89:1-34. doi: 10.1016/S0166-4328(97)00048-x
- Sabban EL, Serova L, Nahvi RJ, Liu X. Potential benefits of intranasal neuropeptide Y include sustained extinction of fear memory. J Neuroendocrinol. 2023;35(11):e13279. doi: 10.1111/jne.13279
- Hasselmo ME, Wyble BP, Wallenstein GV. Encoding and retrieval of episodic memories: Role of cholinergic and GABAergic modulation in the hippocampus. Hippocampus. 1996;6:693-708. doi: 10.1002/(SICI)1098-1063(1996)6:6<693:AID-HIPO 12>3.0.CO;2-W
- Buhlman LM. Heterologous Expression of Alpha6*Nicotinic Acetylcholine Receptors and the Natural Distribution of Alpha6 Subunits. Dissertation. United States: University of Arizona; 2007.
- Nabekura J, Murata O, Ishibashi H, Akaike N. Use-dependent suppression of the nicotinic acetylcholine receptor response by the proadrenomedullin N-terminal 20-amino acid peptide in rat locus coeruleus neurons. J Neurochem. 1998;70:865-870. doi: 10.1046/j.1471-4159.1998.70020865.x
- Takano K, Yamashita N, Fujita T. Proadrenomedullin NH2- terminal 20 peptide inhibits the voltage-gated Ca2+ channel current through a pertussis toxin-sensitive G protein in rat pheochromocytoma-derived PC 12 cells. J Clin Invest. 1996;98(1):14-17. doi: 10.1172/JCI118758
- Hardman JG, Limbird PB, Gilman AG, editors. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York: McGraw-Hill; 2001.
- Iwasaki H, Hirata Y, Iwashina M, Sato K, Marumo F. Specific binding sites for proadrenomedullin N-terminal 20 peptide (PAMP) in the rat. Endocrinology. 1996;137(7):3045-3050. doi: 10.1210/en.137.7.3045
- Li GZ, Liang QC, Jin YH, et al. The effect of acetylcholine on pain-related electric activities in the hippocampal CA3 of rats. J Neural Transm (Vienna). 2011;118(4):555-561. doi: 10.1007/s00702-010-0545
- Wenk GL. Neurodegenerative diseases and memory: A treatment approach. In: Kesner RP, Martinez JL Jr., editors. Neurobiology of Learning and Memory. 2nd ed. Burlington, MA: Academic Press; 2007. p. 621.
- Meldrum BS. Glutamate as a neurotransmitter in the brain: Review of physiology and pathology. J Nutr. 2000;130:1007S-1015S. doi: 10.1093/jn/130.4.1007S
- Rousseaux CG. A review of glutamate receptors II: Pathophysiology and pathology. J Toxicol Pathol. 2008;21(3):133-173. doi: 10.1293/tox.21.133
- Jones PG, Dunlop J. Targeting the cholinergic system as a therapeutic strategy for the treatment of pain. Neuropharmacology. 2007;53:197-206. doi: 10.1016/j.neuropharm.2007.04.002
- Sveinsdottir V, Eriksen HR, Ursin H, Hansen ÅM, Harris A. Cortisol, health, and coping in patients with nonspecific low back pain. Appl Psychophysiol Biofeedback. 2016;41:9-16. doi: 10.1007/s10484-015-9300-2
- Ofek K, Krabbe KS, Evron T, et al. Cholinergic status modulations in human volunteers under acute inflammation. J Mol Med (Berl). 2007;85(11):1239-1251. doi: 10.1007/s00109-007-0226
- Zimmerman G, Soreq H. Termination and beyond: Acetylcholinesterase as a modulator of synaptic transmission. Cell Tissue Res. 2006;326:655-669. doi: 10.1007/s00441-006-0239-8
- Das A, Rai D, Dikshit M, Palit G, Nath C. Nature of stress: Differential effects on brain acetylcholinesterase activity and memory in rats. Life Sci. 2005;77(18):2299-2311. doi: 10.1006/phrs.2000.0678
- Gabriel NN, Soliman KFA. Effect of stress on the acetylcholinesterase activity of the hypothalamus-pituitary-adrenal axis in the rat. Horm Res. 1983;17:43-48. doi: 10.1159/000179673
- Sailaja BS, Cohen-Carmona D, Zimmerman G, Soreq H, Meshorer E. Stress-induced epigenetic transcriptional memory of acetylcholinesterase by HDAC4. Proc Natl Acad Sci U S A. 2012;109(52):E3687-E3695. doi: 10.1073/pnas.1209990110
- Tagliari B, Tagliari AP, Schmitz F, da Cunha AA, Dalmaz C, Wyse AT. Chronic variable stress alters inflammatory and cholinergic parameters in hippocampus of rats. Neurochem Res. 2011;36(3):487-493. doi: 10.1007/s11064-010-0367-0
- Grisaru D, Pick M, Perry C, et al. Hydrolytic and nonenzymatic functions of acetylcholinesterase comodulate hemopoietic stress responses. J Immunol. 2006;176:27-35. doi: 10.4049/jimmunol.176.1.27
- Marchi M, Bocchieri P, Garbarino L, Raiteri M. Muscarinic inhibition of endogenous glutamate release from rat hippocampus synaptosomes. Neurosci Lett. 1989;96(2):229-234. doi: 10.1016/0304-3940(89)90063-3
- Soreq H, Yirmiya R, Cohen O, Glick D. Acetylcholinesterase as a window onto stress responses. Tech Behav Neural Sci. 2005;15:585-608. doi: 10.1016/s0921-0709(05)80032-x
- National Institutes of Health. Genbank Basic Local Alignment Search Tool. Washington, DC: National Institutes of Health; 2013. Available from: https://blast.ncbi.nlm.nih.gov/blast. cgi [Last accessed on 2013 Jun 10].
- Mir SA, Razzokov J, Mukherjee V, Baitharu I, Nayak, B. An exploration of the binding prediction of anatoxin-a and atropine to acetylcholinesterase enzyme using multi-level computer simulations. Phys Biol. 2023;21(1):016002. doi: 10.1088/1478-3975/ad0caa
- Dhume RA, Noronha A, Nagwekar MD, Mascarenhas JF. Effect of dorsal hippocampal lesion compared to dorsal hippocampal blockade by atropine on reference memory in vision deprived rats. Indian J Med Res. 1989;90:379-385.
- National Institutes of Health. Pubchem Acetylcholinesterase. Washington, DC: National Institutes of Health; 2024. Available from: https://pubchem.ncbi.nlm.nih.gov/ compound/atropine [Last accessed on 2024 Sep 24].
- Akuzawa N, Obinata H, Izumi T, Shigeki T. Morphine is an exogenous ligand for MrgX2, a G protein-coupled receptor for cortistatin. J Cell Anim Biol. 2007;2(1):4-9.
- Arnold BS, Alpers GW, Sub H, et al. Affective pain modulation in fibromyalgia, somatoform pain disorder, back pain, and healthy controls. Eur J Pain. 2008;12:329-338. doi: 10.1016/j.ejpain.2007.06.007
- Mayer EA, Bushnell MC. Preface. In: Mayer EA, Bushnell MC, editors. Functional Pain Syndromes: Presentation and Pathophysiology. Washington, DC: IASP Press; 2009. p. xv-xviii.
- Sarason IG, Sarason BR. Abnormal Psychology: The Problem of Maladaptive Behavior. 11th ed. Hoboken: Pearson Prentice Hall; 2005.
- von dem Knesebeck O, Lehmann M, Löwe B, Lüdecke D. Causal attributions for somatic symptom disorder. J Psychosom Res. 2020;129:109910. doi: 10.1016/j.jpsychores.2019.109910
- National Institutes of Health. DSM-5 Redefines Hypochondriasis. Rochester, MN: Mayo Clinic; 2013. Available from: https://www.mayoclinic.org/documents/ mc7900-0213-pdf/doc-20079285 [Last accessed on 2024 Sep 24].
- Burba B, Oswald R, Grigaliunien V, Neverauskiene S, Jankuviene O, Chue P. A controlled study of alexithymia in adolescent patients with persistent somatoform pain disorder. Can J Psychiatry. 2006;51:468-471. doi: 10.1177/070674370605100709
- Kuzminskaite E, Vinkers CH, Elzinga BM, Wardenaar KJ, Giltay EJ, Penninx B. Childhood trauma and dysregulation of multiple biological stress systems in adulthood: Results from the Netherlands study of depression and anxiety (NESDA). Psychoneuroendocrinology. 2020;121:104835. doi: 10.1016/j.psyneuen.2020.104835
- Van der Kolk BA, van der Hart O. The intrusive past: The flexibility of memory and the engraving of trauma. Am Imago. 1991;48(4):425-454. 126. Bannon AW, Decker MW, Holladay MW, et al. Broad-spectrum, non-opioid analgesic activity by selective modulation of neuronal nicotinic acetylcholine receptors. Science. 1998;279:77-81. doi: 10.1126/science.279.5347.77
- Di Cesare Mannelli L, Ghelardini C, Calvani M, et al. Neuroprotective effects of acetyl-L-carnitine on neuropathic pain and apoptosis: A role for the nicotinic receptor. J Neurosci Res. 2009;87:200-207. doi: 10.1002/jnr.21815
- Coutinho MR, Menescal-de-Oliveira L. Role of homocysteic acid in the guinea pig (Cavia porcellus) anterior cingulate cortex in tonic immobility and the influence of NMDA receptors on the dorsal PAG. Behav Brain Res. 2010;208:237-242. doi: 10.1016/j.bbr.2009.11.047
- Vincler M, McIntosh JM. Targeting the alpha9alpha10 nicotinic acetylcholine receptor to treat severe pain. Expert Opin Ther Targets. 2007;11:891-897. doi: 10.1517/14728222.11.7.891
- Vincler M, Wittenaur S, Parker R, Ellison M, Olivera BM, McIntosh JM. Molecular mechanism for analgesia involving specific antagonism of alpha9alpha10 nicotinic acetylcholine receptors. Proc Natl Acad Sci U S A. 2006;103(47):17880-17884. doi: 10.1073/pnas.0608715103
- Amat J, Dolzani SD, Tilden S, et al. Previous ketamine produces an enduring blockade of neurochemical and behavioral effects of uncontrollable stress. J Neurosci 2016;36:153-161. doi: 10.1523/JNEUROSCI.3114-15.2016
- Nwokafor C, Serova LI, Sabban EL. Preclinical findings on the potential of intranasal neuropeptide Y for treating hyperarousal features of PTSD. Ann N Y Acad Sci. 2019;1455(1):149-159. doi: 10.1111/nyas.14172