• Korean Journal of Acupuncture
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• v.38 no.2
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• pp.75-99
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• 2021

Objectives : The purpose of this study is to analyze animal behavioral changes and related neurobiological mechanisms in recent studies using animal models with pain and depression. Methods : We conducted database search in Pubmed, NDSL, and EMBASE up to January 2021. Included studies were classified as depression-like behavior observed in pain model, pain-like behavior observed in depression model, and pain and depression comorbidity model. The results of pain- and depression-like behaviors, the changes of neurobiological mechanisms, and the treatment methods such as drugs, natural substance-derived chemicals, or acupuncture were analyzed. Results : We included 124 studies (81 studies in depression-like behavior observed in pain model, 19 studies in pain-like behavior observed in depression model, and 24 studies in pain and depression comorbidity model). Pain and depression comorbidity animal models were induced using various methods by drugs or surgery. Von frey test, a method for evaluating mechanical allodynia was the most commonly used for measuring pain-like behavior and the forced swimming test was the most commonly used for measuring depression-likes behavior. The changes of neurobiological factors, such as decrease of 5-hydroxytryptamine and increase of oxidative stress and pro-inflammation cytokines were generally changed in the frontal cortex, hippocampus, thalamus, and spinal cord in all types of models. For treating pain and depression-like behaviors, various types of drugs such as antidepressant, tranquilizer, analgesic, and natural substance-derived chemicals were used. Acupuncture treatment was used in 4 studies. Conclusions : In the future, more diverse studies on the combined model of pain and depression need to be conducted. In addition, it is necessary to establish a mechanistic basis for the development of various treatments by identifying the common mechanisms of pain and depression.

• The Korean Journal of Pain
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• v.37 no.2
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• pp.91-106
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• 2024

The mechanisms of the chronic pain and depression comorbidity have gained significant attention in recent years. The complement system, widely involved in central nervous system diseases and mediating non-specific immune mechanisms in the body, remains incompletely understood in its involvement in the comorbidity mechanisms of chronic pain and depression. This review aims to consolidate the findings from recent studies on the complement system in chronic pain and depression, proposing that it may serve as a promising shared therapeutic target for both conditions. Complement proteins C1q, C3, C5, as well as their cleavage products C3a and C5a, along with the associated receptors C3aR, CR3, and C5aR, are believed to have significant implications in the comorbid mechanism. The primary potential mechanisms encompass the involvement of the complement cascade C1q/C3-CR3 in the activation of microglia and synaptic pruning in the amygdala and hippocampus, the role of complement cascade C3/C3a-C3aR in the interaction between astrocytes and microglia, leading to synaptic pruning, and the C3a-C3aR axis and C5a-C5aR axis to trigger inflammation within the central nervous system. We focus on studies on the role of the complement system in the comorbid mechanisms of chronic pain and depression.

• Korean Journal of Acupuncture
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• v.41 no.3
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• pp.79-89
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• 2024

Objectives : We aimed to identify the effects of acupuncture treatment on alleviating pain and depression and modulating brain neural activity in the neuropathic pain and depression comorbidity mouse model (PDCM). Methods : We performed partial sciatic nerve ligation on the right hind paw of mice to induce neuropathic pain and injected reserpine (2 mg/kg, intraperitoneal) for 10 days from the day of the surgery to induce pain and depression. Acupuncture treatment was performed for 10 days at the following locations: 1) ST36 and SP6 (Joksamni and Sameumgyo; JS), 2) KI1 and HT7 (Yongcheon and Sinmun; YS), 3) LR1, PC9, KI10, and PC3 (Pericardium tonification; PT), or 4) LR1, HT9, KI10, and HT3 (Heart tonification; HT). Pain-like behavior was measured using the von Frey test and depressive-like behavior was assessed using the open field test. Then, the c-Fos expression was analyzed in the brain regions of neocortex, striatum, hypothalamus, hippocampus, midbrain, and medulla to examine brain neural activity. Results : In PDCM, pain-like behavior was alleviated by acupuncture treatment on the JS, YS, PT, and HT, and depressive-like behavior was improved by acupuncture treatment on the JS and YS. JS and YS were derived as an optimized acupoint combination for improving neuropathic pain and depression comorbidity. Brain neural activities in the neocortex (infralimbic cortex) and hypothalamus (paraventricular hypothalamic nucleus; PVN) were commonly altered by both JS and YS acupuncture treatments. In addition, neural activities in the neocortex (prelimbic cortex; PrL) and midbrain (substantia nigra, lateral part of the dorsal raphe nucleus) were altered exclusively by JS acupuncture treatment, while changes in the area 2 of the anterior cingulate cortex and the cornu ammonis 3 of the hippocampus were specific to YS acupuncture treatment. Brain neural activity in the PrL and PVN regions was significantly correlated with changes in pain behavior. Conclusions : Both JS and YS acupuncture treatments alleviated pain and depressive-like behaviors, which were associated with modulation of neural activities in the neocortex, hypothalamus, hippocampus, and midbrain.

• CELLMED
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• v.2 no.2
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• pp.15.1-15.3
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• 2012

Kampo medicine, a Japanese traditional herbal medicine, has been used in clinical practice in Japan. The most appropriate Kampo formula should be chosen for each individual by the four diagnostic procedures. Fuku shin, the abdominal exam, is one of the most important approaches in the procedures. There are several abdominal conformations (signs) when administering Fuku shin. In Kampo medicine, psychiatric illness-marked by depression and anxiety-has been shown to be related with an abdominal conformation, Shin ka hi koh (Epigastric Obstructive Hardness). The aim was to see the occurrence of abdominal conformations in each level of depression and anxiety symptoms. Two hundred fifteen patients were assigned to high-, moderate-, or low-level psychiatric comorbidity based on the Hospital Anxiety and Depression Scale and were studied regarding the occurrence of major abdominal conformations. Moderate and high psychopathological groups showed the higher occurrence of Shin ka hi koh [Low, 21%; Moderate, 67%; High, 74%] ($p$ < 0.0001). In conclusion, moderate and high psychopathological patients showed the higher occurrence of a specific abdominal sign.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.3
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• pp.217-225
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• 2021

Neuropathic pain (NP) that contributes to the comorbidity between pain and depression is a clinical dilemma. Neuroinflammatory responses are known to have potentially important roles in the initiation of NP and depressive mood. In this study, we aimed to investigate the effects of paeoniflorin (PF) on NP-induced depression-like behaviors by targeting the hippocampal neuroinflammation through the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway. We used a murine model of NP caused by unilateral sciatic nerve cuffing (Cuff). PF was injected intraperitoneally once a day for a total of 14 days. Pain and depression-like behavior changes were evaluated via behavioral tests. Pathological changes in the hippocampus of mice were observed by H&E staining. The levels of proinflammatory cytokines in the hippocampus were detected using ELISA. Activated microglia were measured by immunohistochemical staining. The TLR4/NF-κB signaling pathway-associated protein expression in the hippocampus was detected by western blotting. We found that the PF could significantly alleviate Cuff-induced hyperalgesia and depressive behaviors, lessen the pathological damage to the hippocampal cell, reduce proinflammatory cytokines levels, and inhibit microglial over-activation. Furthermore, PF downregulated the expression levels of TLR4/NF-κB signaling pathway-related proteins in the hippocampus. These results indicate that PF is an effective drug for improving the comorbidity between NP and depression.

• Korean Journal of Psychosomatic Medicine
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• v.25 no.1
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• pp.56-62
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• 2017

Objectives : The objective of this study was to investigate the relationship between psychological distress and pain in cancer patients. Methods : 249 patients with cancer who visited National Health Insurance Service Ilsan Hospital between April 2013 and March 2014 were evaluated with National Cancer Center Psychological Symptom Inventory(NCC-PSI) which consisted of Modified Distress Thermometer(MDT) and Modified Impact Thermometer(MIT). Each scale was divided into 3 subscales targeting separate symptoms: insomnia, anxiety, and depression. Psychological distress was defined as positive for those who scored above the cutoff values in at least one of all six subscales. The Numeric Rating Scale for Pain(NRS-Pain) was used to assess the subjective severity of pain. Logistic regression was performed to investigate the association between psychological distress and pain. Results : Univariate logistic regression analysis showed that pain, gender, compliance, and two subscale scores of Hospital Anxiety and Depression Scale(HADS) were significantly associated with psychological distress. Multivariate logistic regression analysis showed that pain and HADS anxiety subscale score maintained a statistically significant association with psychological distress adjusted for variables including age, gender, years of education, Eastern Cooperative Oncology Group performance status, cancer stage, Charlson Comorbidity Index, compliance, and HADS depression subscale score. One point increase in pain was 1.31 times more likely to cause psychological distress. In secondary analysis, pain was significantly associated with all subscales of NCC-PSI, except MIT-anxiety subscale. Conclusions : This study suggests that NCC-PSI, a screening tool for psychological distress, reflects pain. We recommend that physicians who treat cancer patients consider the examination of psychological distress which provides comprehensive evaluation of various factors regarding quality of life.

• The Korean Journal of Pain
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• v.37 no.2
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• pp.107-118
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• 2024

Nociplastic pain by the "International Association for the Study of Pain" is defined as pain that arises from altered nociception despite no clear evidence of nociceptive or neuropathic pain. Augmented central nervous system pain and sensory processing with altered pain modulation are suggested to be the mechanism of nociplastic pain. Clinical criteria for possible nociplastic pain affecting somatic structures include chronic regional pain and evoked pain hypersensitivity including allodynia with after-sensation. In addition to possible nociplastic pain, clinical criteria for probable nociplastic pain are pain hypersensitivity in the region of pain to non-noxious stimuli and presence of comorbidity such as generalized symptoms with sleep disturbance, fatigue, or cognitive problems with hypersensitivity of special senses. Criteria for definitive nociplastic pain is not determined yet. Eight specific disorders related to central sensitization are suggested to be restless leg syndrome, chronic fatigue syndrome, fibromyalgia, temporomandibular disorder, migraine or tension headache, irritable bowel syndrome, multiple chemical sensitivities, and whiplash injury; non-specific emotional disorders related to central sensitization include anxiety or panic attack and depression. These central sensitization pain syndromes are overlapped to previous functional pain syndromes which are unlike organic pain syndromes and have emotional components. Therefore, nociplastic pain can be understood as chronic altered nociception related to central sensitization including both sensory components with nociceptive and/or neuropathic pain and emotional components. Nociplastic pain may be developed to explain unexplained chronic pain beyond tissue damage or pathology regardless of its origin from nociceptive, neuropathic, emotional, or mixed pain components.

• The Journal of Korean society of community based occupational therapy
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• v.9 no.1
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• pp.35-45
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• 2019

Objective : The purpose of this study was to investigate the factors influencing stroke in community-dwelling adults. Methods : This study used raw data from the community health survey in 2016. Among the 228,452 subjects who participated in the survey, 225,003 (98.5%) of them were included in the analysis of this study. The sociodemographic characteristics were selected as gender, age, region, income, marital status, and comorbidity was selected as osteoporosis, hypertension, diabetes, dyslipidemia, myocardial infarction and arthritis. Health-related quality of life was assessed by EuroQol-5 Dimension(EQ-5D) and the subcategory of EQ-5D (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) were included in the analysis. Dependent variables were stroke, and the independent variables were the 16 variables described above. Statistical analysis was performed using binomial logistic regression analysis. Results : In sociodemographic variables, stroke was predicted by men, aging, and lower income levels. In comorbidity variables, stroke was predicted by hypertension, diabetes mellitus, hyperlipidemia, and myocardial infarction. In sub-domains of health-related quality of life, stroke was predicted by self-care, usual activities, mobility, anxiety/depression, and pain/discomfort. Conclusion : These finding suggest that it is needed development of a customized health promotion program for the improvement of self-care and activities of daily living in community-dwelling stroke survivors.

• Korean Journal of Psychosomatic Medicine
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• v.25 no.2
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• pp.129-135
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• 2017

Objectives : Little is known about the influence of urinary incontinence and depression on individual's QOL(Quality of life). We aimed to clarify how the interaction between urinary incontinence and depression influences one's QOL. Methods : A total of 1262 patients were enrolled in this study from April, 2011 to July, 2011. We estimated the severity of depressive symptoms and QOL, using SGDS-K, EQ-5D. We also investigated the morbidity of urinary incontinence for each patient in person or by questionnaire. Comparisons of QOL between groups with or without depression, with or without urinary incontinence were established using t-test, ANOVA and Scheffe's post hoc analysis. The interaction between urinary incontinence and depression was analyzed by each domain of QOL, using multiple regression analysis. Results : Patients with depression and urinary incontinence showed significantly higher EQ-5D scores on every domain of QOL than other patients, which means significantly lower QOL. Patients with depression, no urinary incontinence reported lower QOL, especially in the domain of 'usual activity', 'anxiety' and 'visual analogue scale(VAS)', whereas those with urinary incontinence, no depression showed lower QOL in 'motility', 'usual activities' and 'pain' domain. Statistically significant interaction effects of two diseases were observed in the domain of 'VAS', 'self care' and 'anxiety'. Conclusions : Comorbidity of urinary incontinence and depression showed significantly lower QOL of patients, compared with urinary incontinence or depression respectively, which implies additive interaction effects of the two diseases. Optimal diagnosis and treatment of depression should be emphasized for patients with urinary incontinence.

• Korean Journal of Psychosomatic Medicine
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• v.24 no.2
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• pp.174-183
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• 2016

Objectives : The aim of this study is to evaluate difference of somatic symptoms of anxiety disorder and major depressive disorder and domainal association with suicidal idealization, plan, and attempts. Methods : A total of 359 adults diagnosed with major depressive disorder and anxiety disorder of last one year participated. Participants interviewed with certain sections of Korean version of Composite International Diagnostic interview of CIDI. Sections of interests includes questionnaires regarding somatic symptoms and suicidal idea, plan and attempts of last one year. Results : Chest pain shows more prevalence in major depressive disorder. Symptoms of Headache and loose stool are more prevalent in anxiety disorder. Difficulty in equilibrium and fainting spells are more common somatic complaints of co-diagnosis states of anxiety disorder and major depressive disorder. Comparing 3 domains of pain symptoms, gastrointestinal symptoms and pseudo-neurological symptoms, pain symptom domains, gastrointestinal symptoms domain shows significant statistic difference between diagnosis. Average somatic symptom numbers of each symptom domains increase through suicidal idealization, plan and attempt, accordingly. Conclusions : Our finding shows some of somatic symptoms are more prevalent at certain diagnosis. Since increasing numbers of somatic complaints of each symptom domains goes with the suicidal idealization to suicidal attempts, proper psychiatric evaluation and consultations are crucial for patients with numerous somatic complaints in non-psychiatric clinical settings.