Printer Friendly

Pain manifestations in neuropsychiatry disorders (animal models and human patients). The possible relevance of oxytocin.

GENERAL CONSIDERATIONS ABOUT PAIN

Pain is an undesirable experience that all people encounter at least once in their lifetime. There have been postulated several interpretations in the attempt to define this complex and yet not fully elucidated phenomenon known as pain.

At the present moment the definition that is generally accepted is given by the International Association for the Study of Pain (IASP) which advocates that pain is 'an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage' [1].

The definition itself indicates that this event is not a pure sensory experience but also a perception, element which implies the need of a cognitive processing.

Therefore, it can be noted that pain manifestation is composed of multiple sides such as: a sensory-discriminative side, responsible for locating and/or marking the intensity of pain; a motivational-affective side, representing the emotional reactions that pain creates [2] and also, a cognitive-evaluative side, which is known for the superior processes and memory involvement in the occurrences of pain manifestations [3].

This multifaceted event that pain contours to be gives it a complex outlook and difficult to quantify qualities, shaped to be a highly selective individual experience.

PAIN MANIFESTATIONS IN NEUROPSYCHIATRIC DISORDERS--CLINICAL AND ANIMAL MODELS

Most of the current studies following pain manifestations point to an impaired perception of pain in the context of neuropsychiatric disorders. Knowing that pain is already a difficult event to assess accompanied by a high rate of subjectivity, introducing neuropsychiatric disorders in the disputed point, acknowledged for their severe mental impairments, makes assessment of pain an even more difficult task to achieve.

However, pain manifestations were followed in different psychiatric conditions, either in clinical environment or partially replicated in laboratory conditions. In schizophrenia, a renowned severe debilitating mental illness, the limited number of clinical studies involving human patients recorded in this context showed that pain manifests distinctively in these individuals. As our group previously reviewed [4] the array of reactions encountered in patients suffering from schizophrenia vary from lack of pain sensitivity pointed out by a majority of clinical investigations [5,6], to no significant differences between healthy volunteers and persons diagnosed with this mental condition [7]. Considering that persons with schizophrenia come under a high risk group for different underlined conditions that are not manifesting their classical symptoms [8], as for example the presence of painless myocardial infarction which under normal circumstances is considered a medical emergency causing a great deal of pain, the need of following pain in this mental disorder is imperiously necessary. Although there were researches that did not uncover a difference between pain perception in patients with schizophrenia and their healthy peers [9], others even found that the presence of pain manifestations were increased in schizophrenia symptomatology [10].

Another way to investigate specific disease features is by employing animal models. It was observed that by administering glutamate antagonist like ketamine specific schizophrenia symptoms are replicated. In this way, it was created an animal model of schizophrenia by administering ketamine in sub-anesthetic dosages [11-13]. The ketamine--induced animal model of schizophrenia appears to manifest increased pain tolerance, results similar to the ones registered in human patients suffering from schizophrenic disorder. Our laboratory also tested thermal pain thresholds in the ketamine-induced animal model of schizophrenia and results indicated to an increased pain sensitivity [14], which is in accordance to human individuals reactions [10]. There are also other animal models utilized to create schizophrenia symptoms in laboratory animals, for instance by administering neonatal intracerebroventricular of quinolinic acid and N-acetyl-aspartyl-glutamate. In these models there were also observed modification in the nociceptive perception, a higher thermal pain threshold being recorded. Nonetheless, there were not logged any significant changes in acute mechanical nociception and neither in the formalin test [15]. On the other hand, on the same model of schizophrenic behaviour when it was applied a neuropathic pain model, hyperalgesia was reported [15]. Therefore, the same contradictory results manifest also in animal models of schizophrenia, making the subject of pain in the context of schizophrenic disorder an interesting pursuit to follow.

Alzheimer's disease (AD) is another severe neuropsychiatric condition characterized by neurodegeneration leading to loss of short term memory, as a main symptom. Besides the specific features that accompany this disorder, several studies indicate that alteration of pain perception both acute and chronic is encountered in patients with dementia [16]. The situation of pain manifestations is similar somehow to the one described in the schizophrenic disorder, because perception of pain ranges from lack of it to hypersensitivity [17, 18] as our group anterior demonstrated [19]. Even so, there are cases where it is sustained that

pain manifestations are no different than the ones found in nondemented subjects [20]. An interesting observation is that patients suffering from AD might express their discomfort caused by pain features differently by utilizing behavioural traits such as agitation, aggression, pacing, wandering and sleep disturbances [21].

Affective disorders include a group of mental diseases as anxiety, depression and bipolar disorder [22]. As there is more and more data signaling the strong bond between pain and psychiatric conditions, affective disorders are not excluded from this pain disturbance phenomenon. In the case of depression it appears that the relationship between pain and the psychiatric manifestation is bidirectional, clinical studies indicating to a 50% rate and more expose risk for persons suffering from chronic pain to be also diagnosed with depression, as in the report of Bair et al., 2003. In the same time, individuals experiencing multiple painful encounters are 3 to 5 time more plausible to struggle with depression as well compared to those without painful events, as demonstrated by Magni et al., 1993. A somehow comparable situation is unfolding in the case of anxiety also (Gerrits et al., 2015). Moreover, an association between anxiety and depression is recorded in people undergoing pain events (Williams et al., 2012). In addition, a remarkable connection between pain and bipolar disorder (BD) has been observed in the clinical studies, notable being that people diagnosed with BD also feel more pain, as previously showed by Fornaro and Stubbs, 2015.

OXYTOCIN IN THE CONTEXT OF NEUROPSYCHIATRIC DISORDERS

Oxytocin is a neuropeptide secreted by the paraventricular and supraoptic nuclei located in the hypothalamus [23]. Most known functions of this element are attributed to uterine contractions during birth, the lactation reflex and recently explored functions such as cardiovascular regulation, learning, memory [24], but also beneficial impact on social behaviours in healthy and neuropsychiatric disorders [25-29] and surprisingly an influence in pain modulation [30-31].

There are other reports that describe oxytocin as a modulator of psychiatric symptomatology. For instance, some studies highlight the possible anxiolytic effects that oxytocin might possess [32]. Also, considering that intranasal administration of oxytocin has an influence on emotional reactions and behaviours it created the idea of a potential action that oxytocin might have on mental conditions such as social anxiety disorder, autism and schizophrenia [33, 34]. Knowing that AD besides the main symptom of memory loss is accompanied by depressive traits [35, 36] and anxious behaviour [37] and acknowledging that oxytocin might have a beneficial influence on depression and anxiety [32-34] and even memory enhancement proprieties [24], it could become a strong future candidate in the therapy of dementia.

Thus, although there are several clinical and animal studies made on the matter of oxytocin effect in psychiatric disorders pointing to a positive outcome, there is still need of further researching the reactions of the interactions between psychiatric events and oxytocin efficacy.

OXYTOCIN AND ITS EFFECTS ON PAIN

Oxytocin, currently has gained another perspective once the possibility of utilizing it in the therapy of pain might become a viable option, considering the demonstrated role in pain modulation [30, 31]. Besides the increasing pain threshold proprieties of oxytocin in animal models tested in pain conditions either used by itself [30] or as an enhancer of an old appointed analgesic method represented by acupuncture [31], oxytocin presents analgesic proprieties also when employed in human subjects as highlighted by the few existing researches. In this way, it was demonstrated that by administering intranasal oxytocin in patients suffering from headaches, it might relieve headaches in a dose-dependent manner [38]. Moreover, another study indicates to a significant increase in pain tolerance and threshold when the persons were subjected to cold pressor pain [39]. However, there are still other reports that did not present any analgesic features when oxytocin was administered to the individuals experiencing either experimental or clinical pain [40, 41]. These various results have several reasons incriminated amongst them being the inconsistent sample sizes or the different pain states included in the evaluation [42], but nonetheless there is an obvious need of further researching the possibilities of this neuropeptide, oxytocin.

Considering that a possible mechanism incriminated in prosocial behaviour induced by oxytocin administration in both animal models and humans is due to re duction in stress activity opens new therapeutical possibilities [43, 44]. Adding up that stress amongst other elements is a contributing factor to the occurrence of psychiatric illnesses [45] and also that stress is involved in altering pain perception by increasing its manifestations [46], than it must not be overlooked the possibility of employing oxytocin as an agent which might have a beneficial role in both pain reduction and behavioural rehabilitation. Therefore, it is a really powerful potential candidate in the future therapy of pain and psychiatric symptomatology.

Corresponding author:

ALIN CIOBICA

"Alexandru Ioan Cuza" University Faculty of Biology, Dept. of Research Bdul Carol I, 11 700506, Iasi, Romania Tel :0040751218264; Fax 0040232201472; E-mail : alin.ciobica@uaic.ro

Submission: 21 May 2017

Acceptance: 31 July 2017

ACKNOWLEDGMENTS

Iulia Antioch and Alin Ciobica are supported by a PN-II-RU-TE-2014-4-1886 grant called "A complex study regarding the relevance of oxytocin administration in some animal models of neuropsychiatric disorders", number 120 from 01/10/2015.

REFERENCES

(1.) Merskey H, Watson GD. The lateralization of pain. Pain. 1979; 7:271-280.

(2.) Westlund KN, Willis WD. The Rat Nervous System (Fourth Edition), 2015.

(3.) Melzack R, Casey KL. Sensory, motivational and central control determinants of pain: A new conceptual model. In Kenshalo DR (ed): The Skin Senses, Springfield, IL, Charles C. Thomas, 1968; 423-443.

(4.) Antioch I, Ciobica A, Paulet M, Bild V, Lefter R, Timofte D. Pain manifestations in schizophrenia--clinical and experimental aspects in human patients and animal models. Psychiatria Danubina. 2015; 27:142-152.

(5.) Becker A, Grecksch G, Zernig G, Ladstaetter E, Hiemke C, Schmitt U. Haloperidol and risperidone have specific effects on altered pain sensitivity in the ketamine model of schizophrenia. Psychopharmacology. 2009; 202:579-587.

(6.) Jochum T, Letzsch A, Greiner W, Wagner G, Sauer H, Bar KJ. Influence of antipsychotic medication on pain perception in schizophrenia. Psychiatry Res. 2006; 142:151-156.

(7.) Kuritzky A, Mazeh D, Levi A. Headache in schizophrenic patients: A controlled study. Cephalalgia, 1999; 19:725727.

(8.) Stubbs B, Gaughran F, Mitchell AJ, De Hert M, Farmer R, Soundy A, Rosenbaum S, Vancampfort D. Schizophrenia and the risk of fractures: a systematic review and comparative meta-analysis. Gen Hosp Psychiatry 2015; 37:126-133.

(9.) Stubbs B, Mitchell AJ, De Hert M, Correll CU, Soundy S, Stroobants M, Vancampfort D: The prevalence and moderators of clinical pain in people with schizophrenia:A systematic review and large scale meta-analysis. Schizophrenia Research 2014; 160:1-8.

(10.) Strassnig M, Brar JS, Ganguli R: Body mass index and quality of life in community-dwelling patients with schizophrenia. Schizophr Res. 2003; 62:73-76.

(11.) Becker A, Peter B, Schroeder H, Mann T, Huether G, Grecksch G. Ketamine-induced changes in rat behaviour: a possible animal model of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2003; 27:687-700.

(12.) Becker A, Grecksch G: Ketamine-induced changes in rat behaviour: a possible animal model of schizophrenia. Test of predictive validity. Prog Neuropsychopharmacol Biol Psychiatry 2004; 28: 1267-1277.

(13.) Becker A, Grecksch G, Schroeder H: Pain sensitivity is altered in animals after subchronic ketamine treatment. Psychopharmacology (Berl) 2006; 189:237-247.

(14.) Antioch I. Pain phenomenon in schizophrenia. Berlin Psychiatry Summer School--oral presentation 2015.

(15.) Franek M, Vaculin S, Yamamotova A, Stastny F, Bubemkova-Valesova V, Rokyta R. Pain perception inneurodevelopmental animal models of schizophrenia. Physiol Res. 2010; 59:811-9.

(16.) Farrell MJ, Katz B, Helme RD. The impact of dementia on the pain experience. Pain. 1996; 67:7-15.

(17.) Rainero I, Vighetti S, Bergamasco B, Pinessi L, Benedetti F. Autonomic responses and pain perception in Alzheimer's disease. European Journal of Pain. 2000;4:267-274.

(18.) Jensen-Dahm C., Werner M.U., Dahl J.B., Staehelin Jensen T, Ballegaard M., Hejl Anne-Mette, Waldemar G.. Quantitative sensory testing and pain tolerance in patients with mild to moderate Alzheimer disease compared to healthy control subjects. Pain. 2014; 155:1439-1445

(19.) Antioch I, Ciobica A, Bild V, Anton E, Timofte D. Current knowledge of pain involvement in Alzheimer's disease. Annals of the "Alexandru loan Cuza" University Sect. II a., Genetics and Molecular Biology 2015;16(1):27-36.

(20.) Pickering G, Jourdan D, Dubray C. Acute versus chronic pain treatment in Alzheimer's disease. Eur J Pain. 2006; 10:379-84.

(21.) Coehen-Mansfiel J, Thein K, Marx MS. What are the barriers to performing nonpharmacological interventions for behavioural symptoms in the nursing home? J Am Med Dir Assoc. 2012; 13:400-405.

(22.) O'Shea Brian. Textbook of Psychological Medicine Fifth Edition, The College of Psychiatry of Ireland 2010; pp.379.

(23.) Barberis C, Tribollet, E. Vasopressin and oxytocin receptors in the central nervous system. Crit. Rev. Neurobiol. 1996; 10:119-154.

(24.) McEwen BB. The role of vasopressin and oxytocin in memory processing. Elsevier Science, Amsterdam 2004; vol. 50.

(25.) Ciobica Alin, Balmus Ioana Miruna, Padurariu Manuela. Is oxytocin relevant for the affective disorders? Acta Endocrinologica. 2016; 12 (1):65-71.

(26.) Padurariu Manuela, Prepelita Raluca, Ciobica Alin, Dobrin Romeo, Timofte Daniel, Stefanescu Cristinel, Chirita Roxana. The concept of suicide: neurophysiological/genetic theories and possible oxytocin relevance. Neurophysiology. 2016; 8(4):312-321.

(27.) Manuela Padurariu, Alin Ciobica. Understanding the Importance of Oxytocin in Depression. Nobel Medicus. 2017

(28.) Ebstein RP, Israel S, Lerer E, Uzefovsky F, Shalev I, Gritsenko I, Riebold M, Salomon S, Yirmiya N. Arginine vasopressin and oxytocin modulatehuman social behavior. Ann. N. Y. Acad. Sci. 2009; 1167:87-102.

(29.) Aoki Y, Yahata N, Watanabe T, Takano Y, Kawakubo Y, Kuwabara H et al.. Oxytocin improves behavioural and neuraldeficits in inferring others' social emotions in autism. Brain J. Neurol. 2014; 137:3073-3086.

(30.) Yang J, Yang Y, Chen JM, Liu WY, Wang CH, Lin BC. Central oxytocin enhances antinociception in the rat. Peptides. 2007; 28(5):1113-9.

(31.) Yang J, Yang Y, Chen JM, Liu WY, Wang CH, Lin BC. Effect of oxytocin on acupuncture analgesia in the rat. Neuropeptides. 2007; 41:285-292.

(32.) Heinrichs M, von Dawans B, Domes G. Oxytocin, vasopressin, and human social behavior. Frontiers in Neuroendocrinology. 2009; 30:548-557.

(33.) Meyer-Lindenberg A, Domes G, Kirsch P, Heinrichs M. Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine. Nature Reviews Neuroscience. 2011; 12:524-538.

(34.) Insel TR. The challenge of translation in social neuroscience: a review of oxytocin, vasopressin, and affiliative behavior. Neuron. 2010; 65:768-779.

(35.) Benoit M, Berrut G, Doussaint J, Bakchine S, Bonin-Guillaume S, Fremont P et al. Apathy and depression in mild Alzheimer's disease: a cross-sectional study using diagnostic criteria. J. Alzheimer's Dis. 2012; 31:325-334.

(36.) Olin JT, Schneider LS, Katz IR, Meyers BS, Alexopoulos GS, Breitner JC et al. Provisional diagnostic criteria for depression of Alzheimer's disease: description and review. Expert Rev. Neurother. 2003; 3:99-106.

(37.) Haller J, Kruk MR. Normal and abnormal aggression: human disorders and novel laboratory models. Neurosci Biobehav Rev. 2006; 30:292-303.

(38.) Wang YL, Yuan Y, Yang J, Wang CH, Pan YJ, Lu L et al. The interaction between the oxytocin and pain modulation in headache patients. Neuropeptides. 2013; 47(2):93-7.

(39.) Rash JA, Campbell TS. The effect of intranasal oxytocin administration on acute cold pressor pain: a placebocontrolled, double-blind, within-participants crossover investigation. Psychosom Med. 2014; 76(6):422-9.

(40.) Singer T, Snozzi R, Bird G, Petrovic P, Silani G, Heinrichs M, Dolan RJ. Effects of oxytocin and prosocial behavior on brain responses to direct and vicariously experienced pain. Emotion. 2008; 8(6):781-91.

(41.) Mameli S, Pisanu GM, Sardo S, Marchi A, Pili A, Carboni M, Minerba L et al. Oxytocin nasal spray in fibromyalgic patients. Rheumatol Int. 2014; 34(8):1047-52.

(42.) Tracy LM, Georgiou-Karistianis N, Gibson SJ, Giummarra MJ. Oxytocin and the modulation of pain experience: Implications for chronic pain management. Neurosci Biobehav Rev. 2015; 55:53-67.

(43.) Cardoso C, Kingdon D, Ellenbogen MA. A meta-analytic review of theimpact of intranasal oxytocin administration on cortisol concentrations duringlaboratory tasks: moderation by method and mental health. Psychoneuroendocrinology. 2014; 49:161-170.

(44.) Parker KJ, Buckmaster CL, Schatzberg AF, Lyons DM. Intranasaloxytocin administration attenuates the ACTH stress response in monkeys. Psychoneuroendocrinology. 2005; 30:924-929.

(45.) Agid O, Kohn Y, Lerer B. Environmental stress and psychiatric illness. Biomed Pharmacother. 2000; 54(3):135-41.

(46.) Heidari J, Mierswa T, Kleinert J, Ott I, Levenig C, Hasenbring M, Kellmann M. Parameters of low back pain chronicity among athletes: Associations with physical and mental stress. Physical Therapy in Sports. 2016; 21: 31-37.

Iulia Antioch--PhD student, Department of Research, Faculty of Biology, "Alexandru loan Cuza" University, Bd. Carol I, nr. 11, Iasi, 700506, Romania

Vasile Chirita--MD, PhD, senior psychiatry, Honorary Member of Romanian Academy

Roxana Chirita-MD, PhD, senior psychiatrist, professor, Gr.T.Popa University of Medicine and Pharmacy, Iasi, Socola Institute of Psychiatry Iasi

Gabriel Ovidiu Oprisanu-MD, Socola Institute of Psychiatry Iasi

Irina Dobrin-MD, PhD, senior psychiatrist, Assistant of professor, Gr.T.Popa University of Medicine and Pharmacy, Iasi, Socola Institute of Psychiatry Iasi

Alin Ciobica--Principal Researcher II, Department of Research, Faculty of Biology, "Alexandru Ioan Cuza" University, Bd. Carol I, nr. 11, Iasi, 700506, Romania

Center of Biomedical Research of the Romanian Academy, Iasi Branch, 700505, Iasi, Romania, The Academy of the Romanian Scientists, Bucharest, Splaiul Independentei 54, 050094, Romania
COPYRIGHT 2017 Institute of Psychiatry Socola, Iasi
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2017 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Author:Antioch, Iulia; Chirita, Vasile; Chirita, Roxana; Ovidiu Oprisanu, Gabriel; Dobrin, Irina; Ciobica,
Publication:Bulletin of Integrative Psychiatry
Article Type:Report
Date:Sep 1, 2017
Words:2974
Previous Article:The effects of magnesium antidepressants co-administration on the spontaneous behaviour in old rats.
Next Article:A Psychological Function of Sacrifices in Romanian Construction Rites.
Topics:

Terms of use | Privacy policy | Copyright © 2021 Farlex, Inc. | Feedback | For webmasters |