Comorbid Pain Research Articles

Efficiency of cannabis and cannabidiol in managing chronic pain syndromes: A comprehensive narrative review.

Chronic pain affects up to 40% of adults, contributing to high medical expenses, the loss of productivity, reduced quality of life (QoL), and disability. Chronic pain requires detailed diagnostic assessment, treatment and rehabilitation, yet approx. 80% of patients report inadequate pain management. As new treatment options are needed, we aimed to explore the effectiveness of medical cannabis-based products in managing chronic pain, with a particular focus on treatment patterns.We searched the PubMed, Scopus and Web of Science databases using keywords related to cannabinoids and chronic pain syndromes. In total, 3,954 articles were identified, and 74 studies involving 12,562 patients were included. The effectiveness of cannabis-based products varied across studies. Cannabinoids were most effective in treating chronic secondary headache and orofacial pain, chronic secondary musculoskeletal pain, chronic secondary visceral pain, and chronic neuropathic pain. Properly qualifying patients is the first crucial step in managing chronic pain, considering pain characteristics, comorbidities and other treatment options. Treatment should start with low doses of cannabinoids, which are then increased to achieve the desired therapeutic effect while minimizing adverse effects.This narrative review revealed significant gaps in the evidence regarding precise treatment patterns, particularly for the long-term maintenance treatment needed by patients with chronic pain. Medical cannabis can be considered an option for carefully selected patients with chronic pain syndromes when other treatment options fail to achieve an adequate response, and when the potential benefits outweigh the risks. However, there is still a need for well-designed clinical research to establish the long-term efficacy and safety of cannabinoids.

The role of immunity in comorbid pain and depression

The narrative review aims to shed light on the influence of inflammation in the comorbid chronic pain and major depressive disorder (MDD). This connection is known to be multifactorial, with a dynamic interaction between genetic and epigenetic factors. However, a growing body of evidence has shown that the co-presence of MDD and pain is underlain by immune mechanisms involved in the persistence of the inflammatory process. In particular, the cytokines released following activation of the innate immune system during inflammation cause changes at the endocrine level that result in glucocorticoid resistance, as well as altering the synthesis and metabolism of some central nervous system (CNS) mediators. Cytokines appear to generate neuroinflammation by activating normally protective microglia. Various other mechanisms, including changes in the function of the glutamatergic, GABAergic, and serotonergic systems are also implicated, but inflammation-induced reduction of BDNF (brain-derived neurotrophic factor) appears to be the deciding factor. In turn, neuroinflammation leads to sickness behavior, which is characterized by anhedonia and social withdrawal. This review explored these mechanisms, which may be at the root of comorbid pain and MDD. Although intriguing, however, most available evidence comes from animal studies, and rigorous clinical exploration is warranted.

The phenotype of recovery XII: A reinforcer pathology perspective on associations between delay discounting and pain catastrophizing in substance use disorder recovery

BackgroundSubstance use disorder (SUD) and pain are highly comorbid conditions and several pain indices (e.g., pain intensity) are associated with an increased risk of relapse. However, the cognitive-emotional experience of pain (i.e., pain catastrophizing) is understudied in SUD recovery. Further, how the association between pain catastrophizing and delay discounting - a posited biomarker of addiction, impacts multidimensional aspects of SUD recovery, including remission and quality of life (QOL), has yet to be examined. MethodsIndividuals (n = 170) in SUD recovery reporting pain were asked about their chronic pain status, completed the Brief Pain Inventory, the Pain Catastrophizing Scale, an Adjusting Amount Delay Discounting Task, and the World Health Organization QOL-BREF scale. Univariate logistic and linear regressions examined associations between delay discounting and several pain indices with remission and QOL. Mediation analyses were investigated whether pain catastrophizing mediates the relationship between delay discounting and 1) sustained remission and 2) QOL. ResultsSignificant negative associations were found between delay discounting (p < .001) and pain catastrophizing (p = .001) with sustained remission. Pain catastrophizing significantly mediated the relationship between delay discounting and physical QOL (p = .044), psychological QOL (p = .009), social (p = .018), and environmental QOL (p = .014). Pain catastrophizing did not mediate the relationship between DD and sustained remission. ConclusionIndividuals with greater DD exhibited greater pain catastrophizing, contributing to poorer QOL in SUD recovery. Our findings support that a Reinforcer Pathology framework is useful to understanding the cognitive-emotional experience of pain within the context of SUD recovery. Interventions that target both delay discounting and maladaptive cognitive and emotional responses to pain may lessen the negative impact of pain on SUD recovery and improve SUD outcomes.

Early pain findings in infants with brachial plexus birth injury: Relationship with function and comorbidities, and cut-off point for fractures

BackgroundInfants with birth brachial plexus injury (BPBI) may have various comorbidities such as fractures, torticollis, plagiocephaly, central nervous system disorders. In infants with BPBI, it is important to identify fractures, which are common among comorbidities, objectively assess pain, and investigate factors that may be associated with pain. AimThe aim of this study is to determine the pain level, comorbidities, and motor function in infants with BPBI and to examine the relationship between these parameters. The second aim is to determine the cut-off value of the pain score that may be a sign of fracture in patients with BPBI, in order to suspect and predict a fracture in the shoulder region and to request additional examinations. Subjects and measurements59 infants with BPBI aged 15–90 days were included in the study. Comorbidities, active joint movements, and total upper extremity function assessed with the Active Movement Scale and pain scores measured with the FLACC Pain Scale were retrospectively analyzed. In addition, pain, comorbidities and motor function were investigated according to types of Narakas, which indicates the degree of nerve injury. ResultsOf the 59 participants, 18 (30.5 %) had at least one comorbidity and 12 (20.3 %) had fractures. The number of comorbidities (p = 0.41), the number of fractures (p = 0.84), and the level of pain (p = 0.71) did not differ by types of Narakas. There was a moderate negative correlation between pain level and upper extremity motor function in upper trunk injuries (p < 0.5, −0.67 < r < −0.46). There was a difference in pain level measured by palpation (p < 0.01) and passive joint movement (p < 0.01) in infants with and without comorbidities. To suspect a fracture in the shoulder region and to request further evaluation, the cut-off value of the Flacc pain level, which may predict a fracture, was 3.5 points for palpation and passive shoulder abduction and 4.5 points for passive external rotation. ConclusionThis is the first study in the BPBI to measure pain in infants using a quantifiable and widely used assessment. Pain level was ranked from high to low as infants with fractures, infants with comorbidities other than fractures and infants without comorbidities. Increased pain adversely affects motor function and pain above the cut-off values is a predictor of fracture.

Infralimbic-basolateral amygdala circuit associated with depression-like not anxiety-like behaviors induced by chronic neuropathic pain and the antidepressant effects of electroacupuncture

Chronic pain, such as neuropathic pain, can lead to anxiety, depression, and other negative emotions, thereby forming comorbidities and increasing the risk of chronic pain over time. Both the infralimbic amygdala (IL) and the basolateral amygdala (BLA) are significantly associated with negative emotions and pain, and they are known to have reciprocal connections. However, the role of IL-BLA circuit pathways in neuropathic pain-induced anxiety and depression remains unexplored. Electroacupuncture (EA) is frequently employed in the treatment of chronic pain and emotional disorders. However, The mechanism by which EA mediates its analgesic and emotion-alleviating effects via the IL-BLA circuit remains uncertain. Here, we used chemogenetic manipulation combined with behavioral tests to detect pain induced anxiety-like and depression-like behaviors. We observed that activation of the IL-BLA circuit by chemogenetic activation induced depression-like behavior of mice. Additionally, we discovered that chemogenetic activation of the IL-BLA circuit successfully prevented the beneficial effects of EA on depression-like behavior brought on by chronic pain in mice with spared nerve injury (SNI). We discovered that SNI-induced depression-like behavior could be mitigated by inhibiting the circuit, and EA had a comparable depressive-relieving effect. Furthermore, the IL-BLA circuit's activation or inhibition had no effect on the anxiety-like feelings brought on by SNI. Overall, our findings identify a specific neural circuit that selectively regulates pain-induced depression-like emotions, without affecting pain-induced anxiety-like emotions. This discovery offers a precise target for future treatments of comorbid pain and depression and provides a plausible explanation for the efficacy of EA in treating depression-like emotions associated with chronic pain.

Insomnia and Chronic Pain Mediate the Relationship Between Traumatic Brain Injury and Reduced Positive Airway Pressure Adherence Among Veterans

Objective: To examine whether co-morbid insomnia, post-traumatic stress disorder (PTSD), depression, and chronic pain mediate the relationship between traumatic brain injury (TBI) and positive airway pressure (PAP) treatment adherence. Setting: One Veterans Health Administration (VHA) sleep medicine site. Participants: Veterans (n = 8836) who were prescribed a modem-enabled PAP device. Design: Secondary analysis of clinical data. We used path analysis to examine: (1) whether Veterans with a history of TBI were more likely to experience insomnia, PTSD, depression, and chronic pain; (2) in turn, whether Veterans with these co-morbid conditions exhibited lesser PAP adherence; and (3) whether Veterans with a history of TBI will exhibit lesser PAP adherence, even while accounting for such co-morbid conditions. Model estimates were adjusted for sociodemographic (eg, race/ethnicity) and clinical characteristics (eg, mask leakage). Main Measures: Health conditions were abstracted from the VHA medical record. PAP adherence was measured using average nightly use (hours). Results: Among 8836 Veterans, 12% had a history of TBI. TBI history was not associated with PAP adherence when accounting for the presence of insomnia, PTSD, depression, and chronic pain. Indirect effect estimates indicated that a history of mild, moderate-severe, or unclassified TBI was associated with lesser PAP adherence, as mediated by the presence of co-morbid insomnia and chronic pain. Generally, TBI was associated with an increased likelihood of co-morbid insomnia, PTSD, depression, and chronic pain. In turn, insomnia and chronic pain, but not PTSD or depression, were associated with lesser PAP adherence. Conclusions: Our study offers empirical support for insomnia and chronic pain as potential explanatory mechanisms underlying the relationship between TBI history and suboptimal PAP adherence. While additional research is needed to confirm causality, findings offer preliminary evidence that can inform the development of tailored PAP adherence interventions for Veterans with TBI and obstructive sleep apnea.

Providing a new transdiagnostic emotion-focused pain treatment in a clinical context: therapists' experiences of facilitators and barriers.

Providing new psychological treatments in clinical settings requires implementation strategies adapted to the organizational context. This study explored how licensed psychologists experienced their context when providing a new transdiagnostic psychological treatment, "the hybrid treatment", to treat comorbid pain and emotional problems in a clinical setting. We aimed to identify which contextual factors the therapists experienced as facilitating or hindering, to gain a better understanding of important considerations when planning a future implementation strategy. Contextual factors were identified using the Consolidated Framework of Implementation Research (CFIR) in data collection and analysis. Data were collected through semi-structured interviews (N = 9). Thematic analysis resulted in the identification of five main influencing factors: Perception of the intervention's adaptability, prioritization of the patient's needs, leadership engagement, structure for collaboration, and therapists' professional engagement. The results highlight the importance of ensuring a clearly stated mandate for the key individuals involved. The findings may guide future implementation of new psychological treatments into regular care, to enhance facilitators and overcome barriers.

Brain predicted age in chronic pelvic pain: a study by the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network.

The effect of chronic pain on brain-predicted age is unclear. We performed secondary analyses of a large cross-sectional and 3-year longitudinal data set from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network to test the hypothesis that chronic pelvic pain accelerates brain aging and brain aging rate. Brain-predicted ages of 492 chronic pelvic pain patients and 72 controls were determined from T1-weighted MRI scans and used to calculate the brain-predicted age gap estimation (brainAGE; brain-predicted - chronological age). Separate regression models determined whether the presence of chronic pelvic pain could explain brainAGE and brain aging rate when accounting for covariates. We performed secondary analyses to understand whether brainAGE was associated with factors that subtype chronic pelvic pain patients (inflammation, widespread pain, and psychological comorbidities). We found a significant association between chronic pelvic pain and brainAGE that differed by sex. Women with chronic pelvic pain had higher brainAGE than female controls, whereas men with chronic pelvic pain exhibited lower brainAGE than male controls on average-however, the effect was not statistically significant in men or women when considered independently. Secondary analyses demonstrated preliminary evidence of an association between inflammatory load and brainAGE. Further studies of brainAGE and inflammatory load are warranted.

Characteristics of men and women with medically diagnosed cluster headache in a national integrated healthcare system: A Veterans Health Administration cohort study.

Describe the epidemiology of cluster headache (CH) using Veterans Health Administration (VHA) Electronic Health Record (EHR) data. Epidemiologic studies of CH at the population level are difficult because it has a prevalence of ~0.1%. Hospital system-wide studies are an attractive alternative as they have large numbers of patients and broader populations than headache or neurology clinic-based studies. The VHA is an ideal hospital-based system in which to study CH because it is nationwide, predominantly male, has a strong focus on mood disorders and suicidality, and has accessible individual medical records. Here, we report the first headache study based on an ongoing longitudinal cohort of patients with CH using VHA EHR data. The VHA EHR data were accessed from Fiscal Year 2008 to 2019. Patients with CH consisted of all patients with at least one outpatient visit containing a CH diagnosis code from the International Classification of Diseases (ICD)-9 or -10. We extracted data on demographic features, incidence, and prevalence, as well as pain and psychiatric comorbidities. Of the 1,524,960 distinct patients who presented for headache treatment in the VHA between Fiscal Year 2008-2019, 24,131 had at least one visit with a CH diagnosis. The 1-year period prevalence of a CH diagnosis in the VHA ranges from 0.08% to 0.10% for women and 0.10% to 0.18% for men. A larger proportion of women versus men received a diagnosis of unspecified CH (59.6% [1412/2368] vs. 53.6% [11,663/21,763], p < 0.001). Most patients with CH had both comorbid headache and non-headache pain diagnoses. Headache not-otherwise-specified was the most common comorbid headache disorder at 70.0% (16,885/24,131) and was more common in women (76.1%, 1801/2368) compared to men (69.3%, 15,084/21,763). Other common comorbidities included migraine, depression, tobacco use, and obstructive sleep apnea. Rates of suicidal ideation or attempt were almost 50% higher in women (5-year proportion 9.4%, 222/2368) with CH compared to men (6.6%, 1433/21,763). To our knowledge this is the largest hospital system study of CH to date and reinforces several previous studies. Pain, mental health, and sleep disorders comorbidities are particularly prevalent in this group and were often more common in women compared to men with CH. Future work should examine gender and race stratified prevalence estimates within the VHA and other healthcare systems.

Veterans in Northern Ireland: Evaluation of chronic pain experience, service type, and physical and mental health functioning

Background Chronic pain is common and associated with disruptions in quality of life (QoL) and psychosocial functioning. These issues are particularly pronounced in veterans, although data in this regard primarily come from the United States Veterans Affairs System, meaning less is known regarding veterans of other countries and regions. The present study evaluated veterans living in Northern Ireland (NI), a region with historic high rates of both chronic pain and psychosocial difficulties associated with the decades-long period of civil and military conflict preceding the 1999 armistice (the Good Friday Agreement). Unique to the Northern Ireland military operation was the initiation of Home Service battalions comprised of local recruits, a role with increased risk due to the conflict’s nature and the fact that they were serving as a military and security presence in their home region. Methods A cross-sectional assessment of veterans living in Northern Ireland ( N = 722) provided details of service type (Home Service vs other service), current health conditions (including chronic pain), and current psychosocial functioning (including physical and mental health QoL, anxiety, depression, and post-traumatic stress disorder [PTSD] symptoms). Results Findings indicated that those with chronic pain had worse QoL, anxiety, depression, and PTSD. Those with chronic pain were also more likely to have served in the Home Services, be unemployed, and be receiving disability payment. Contrary to hypotheses, there was no interaction between chronic pain and service type. Conclusions These results extend previous work with veterans to the unique circumstances of a post-conflict military that engaged in operations within its own country and underscore the need for coordinated, efficacious interventions for co-morbid chronic pain and anxiety, depression, and PTSD.

The association of pain screening and pain level with suicide among US veterans with comorbid musculoskeletal and bipolar disorder diagnoses

BackgroundHigh suicide rates are documented among persons with bipolar disorder diagnoses and pain diagnoses, but few studies have examined the association of pain with suicide mortality in individuals with comorbid pain and bipolar disorders. This study assessed the association of pain screening and pain severity with suicide mortality among veterans with comorbid bipolar and musculoskeletal disorder (MSD) diagnoses. MethodsA retrospective cohort study was conducted on 168,021 patients within the Veterans Health Administration (VHA) who received an MSD diagnosis from 2000 to 2015 and had a bipolar disorder diagnosis. Pain severity, comorbidities, demographics, and suicide mortality were extracted from VHA databases. Poisson regression examined relative risk of suicide by the presence pain screening and pain severity ratings. ResultsPain was assessed in 72.73 % of veterans. Suicide risk was greater in those not assessed (0.98 % versus 0.77 % in assessed group). However, this result did not persist after adjusting for covariates (RR = 1.06). Among those assessed, higher suicide risk was associated with moderate (RR = 1.10), severe pain (RR = 1.06), and no pain (reference) relative to mild pain (RR = 0.99). Major depression, substance use disorders, and prescribed opioids and benzodiazepines increased risk. LimitationsData were obtained from medical records; diagnoses were not confirmed via formal assessment, and no information was available on actual medication use or purpose. Over 25 % of the sample were missing pain severity ratings, which could have affected results. ConclusionsSuicide risk factors among persons with bipolar disorder are complex and multifactorial. Providers should prioritize suicide prevention efforts following new onset or worsening pain.

Psychological Distress Among Ethnically Diverse Participants From Eastern and Southern Africa

Psychological distress is characterized by anxiety and depressive symptoms. Although prior research has investigated the occurrence and factors associated with psychological distress in low- and middle-income countries, including those in Africa, these studies' findings are not very generalizable and have focused on different kinds of population groups. To investigate the prevalence and characteristics (sociodemographic, psychosocial, and clinical) associated with psychological distress among African participants. This case-control study analyzed data of participants in the Neuropsychiatric Genetics in African Populations-Psychosis (NeuroGAP-Psychosis) study, which recruited from general outpatient clinics in Eastern (Uganda, Kenya, and Ethiopia) and Southern (South Africa) Africa. Individuals who participated in the control group of NeuroGAP-Psychosis from 2018 to 2023 were analyzed as part of this study. Data were analyzed from May 2023 to January 2024. The prevalence of psychological distress was determined using the Kessler Psychological Distress Scale (K10), which measures distress on a scale of 10 to 50, with higher scores indicating more distress. Participants from the NeuroGAP-Psychosis study were categorized into cases as mild (score of 20-24), moderate (score of 25-29), and severe (score of 30-50), and participants with scores less than 20 were considered controls. Factors that were associated with psychological distress were examined using binomial logistic regression. From the data on 21 308 participants, the mean (SD) age was 36.5 (11.8) years, and 12 096 participants (56.8%) were male. The majority of the participants were married or cohabiting (10 279 participants [48.2%]), most had attained secondary education as their highest form of learning (9133 participants [42.9%]), and most lived with their families (17 231 participants [80.9%]). The prevalence of mild, moderate, and severe psychological distress was 4.2% (869 participants), 1.5% (308 participants), and 0.8% (170 participants), respectively. There were 19 961 participants (93.7%) who served as controls. Binomial logistic regression analyses indicated that the independent associations of psychological distress were experience of traumatic events, substance use (alcohol, tobacco, or cannabis), the physical comorbidity of arthritis, chronic neck or back pain, and frequent or severe headaches. In this case-control study among ethnically diverse African participants, psychological distress was associated with traumatic stress, substance use, and physical symptoms. These findings were observed to be consistent with previous research that emphasizes the importance of traumatic events as a factor associated with risk for psychopathology and notes the frequent co-occurrence of conditions such as physical symptoms, depression, and anxiety.

The pain and mental health comorbidity.

The pain and mental health comorbidity.

Effect of comorbid psychologic and somatic symptom trajectories on early onset substance use among U.S. youth in the ABCD study

BackgroundAdolescent substance use (SU) is often motivated by a desire to alleviate undesirable symptoms. To test the self-medication hypothesis, we examined associations between comorbid psychologic and somatic symptom trajectories across early adolescence and early onset SU. MethodsUsing Adolescent Brain Cognitive Development Study® data, we differentiated youth who reported no SU at baseline based on their comorbid anxiety, depression, pain, somatic and somnolence symptom trajectories. The outcome, early onset SU (by age 13–14 years) was derived from self-reported alcohol (≥full drink), tobacco (full regular/e-cigarette), marijuana, or other drug use over 5 years. Results8311 participants were classified with Asymptomatic (27.8 %), Low/stable (39 %), Moderate/persistent (25.3 %) or High/worsening trajectories (7.9 %) from age 9.97 ± 0.74 to 13.57 ± 0.88 years. Early onset SU was 56 % higher for Moderate-High compared to Asymptomatic-Low symptom trajectory groups (12.5 % vs. 8.5 %; OR 1.56 [95 % CI 1.33, 1.79]). Adjusted for covariates, the High/worsening group was more likely than the Asymptomatic group to report use of any substance (adj.OR 2.13 [95 % CI 1.40, 3.25], Alcohol (adj.OR 2.80 [95 % CI 1.56, 5.02]), Tobacco (adj.OR 2.09 [95 % CI 1.23, 3.55]), and Marijuana (adj.OR 2.33 [95 % CI 1.36, 3.99]). Longitudinal, time-lagged analyses revealed potential feedback effects of earlier depression on subsequent SU, and earlier SU on later depression (p < 0.001). ConclusionHigher comorbid symptom trajectories emerging in late childhood increased the likelihood of early onset SU. Since negative feedback loops may contribute to symptom persistency, ongoing and potentially harmful SU for at-risk youth, addressing comorbid symptoms that emerge during late childhood is warranted.

Inhibitory gamma-aminobutyric acidergic neurons in the anterior cingulate cortex participate in the comorbidity of pain and emotion.

Pain is often comorbid with emotional disorders such as anxiety and depression. Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid neurotransmission. This review primarily aims to outline the main circuitry (including the input and output connectivity) of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons; it also describes the neurotransmitters/neuromodulators affecting these neurons, their intercommunication with other neurons, and their importance in mental comorbidities associated with chronic pain disorders. Improving understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these conditions. However, the mechanisms that regulate gamma-aminobutyric acidergic systems remain elusive. It is also unclear as to whether the mechanisms are presynaptic or postsynaptic. Further exploration of the complexities of this system may reveal new pathways for research and drug development.

Buprenorphine for the Treatment of Military-related PTSD With Treatment-resistant Depression and Unexpected Benefit for Chronic Pain: Case Report.

The prevalence of treatment-resistant depression within global and military populations highlights the need for novel treatment approaches beyond monoamine neurotransmitter modulators. Buprenorphine (BUP), a semi-synthetic partial opioid agonist, is approved for the treatment of opioid use disorder and has shown promise in treating both depression and chronic pain. This case report discusses the use of transdermal BUP in treating a 36 year-old man with treatment-resistant depression with prominent anhedonia, military-related posttraumatic stress disorder, and chronic pain because of barosinusitis. Significant reductions in anxious and depressive symptoms, including in anhedonia, were observed with lasting effects. An unexpected finding was the discontinuation of prescribed hydromorphone for pain, suggesting the potential unique benefit of BUP in treating chronic pain and treatment resistant depression comorbidities. These findings implicate the diverse beneficial potential of BUP in psychiatric treatments for military populations.

Enhancing genetic association power in endometriosis through unsupervised clustering of clinical subtypes identified from electronic health records.

Endometriosis is a complex and heterogeneous condition affecting 10% of reproductive-age women, and yet, it often goes undiagnosed for several years. Limited observed heritability (7%) of large genetic association studies may be attributable to underlying heterogeneity of disease mechanisms. Therefore, we conducted this study to investigate genetic associations across sub-phenotypes of endometriosis. We performed unsupervised clustering of 4,078 women with endometriosis based on known endometriosis risk factors, symptoms, and concomitant conditions. The clusters were characterized by examining electronic health record (EHR) data and comprehensive chart reviews. We then performed genetic association for each cluster with 39 endometriosis-associated loci (Total Nendometriosis cases = 12,350). We identified five sub-phenotype clusters: (1) pain comorbidities, (2) uterine disorders, (3) pregnancy complications, (4) cardiometabolic comorbidities, and (5) HER-asymptomatic. Bonferroni significant loci included PDLIM5 for the cluster 1, GREB1 for cluster 2, WNT4 for cluster 3, RNLS for cluster 4, and ABO for cluster 5. The difference in associations between the groups suggests complex and varied genetic mechanisms of endometriosis and its symptoms. This study enhances our understanding of the clinical patterns of endometriosis sub-phenotypes, showcasing the innovative approach employed to investigate this complex disease.

Effects of educational attainment on comorbidity of pain and depression in Chinese older adults

Pain and depression comorbidity (PD) among older adults in China is common and significantly affects their physical and mental health. The psychosocial factors may affect people's feelings, understanding and expression of pain and depression, leading to inaccurate assessment of this condition. Educational attainment is thought to be associated with either pain or depression. However, we do not yet know the relationship between educational attainment and PD. Using data from the 2018 China Health and Retirement Longitudinal Study in 2018, we analyzed various variables in 7742 individuals aged 60 years and older. Our results indicate significant differences between the PD and non-PD populations in terms of social, lifestyle, and behavioral factors. We observed a significant decrease in the incidence of PD among older adults with higher levels of education (p < 0.001). This association appears to be partially mediated by cognitive ability, suggesting that educational attainment may mitigate the risk of PD through cognitive enhancement. In addition, our analysis shows that the effect of educational attainment on PD is moderated by additional psychosocial factors, including living environment and alcohol consumption patterns. Older adults with higher levels of education tend to live in urban areas and have better control over alcohol consumption, which may contribute to a lower incidence of PD. Therefore, interventions aimed at enhancing cognitive abilities, improving living environments, and promoting healthier lifestyles and habits among older adults could potentially reduce their burden of PD.

Involvement of basolateral amygdala-rostral anterior cingulate cortex in mechanical allodynia and anxiety-like behaviors and potential mechanisms of electroacupuncture.

Chronic pain is highly associated with anxiety. Electroacupuncture (EA) is effective in relieving pain and anxiety. Currently, little is known about the neural mechanisms underlying the comorbidity of chronic pain and anxiety and the EA mechanism. This study investigated a potential neural circuit underlying the comorbid and EA mechanisms. Spared nerve injury (SNI) surgery established the chronic neuropathic pain mouse model. The neural circuit was activated or inhibited using the chemogenetic method to explore the relationship between the neural circuit and mechanical allodynia and anxiety-like behaviors. EA combined with the chemogenetic method was used to explore whether the effects of EA were related to this neural circuit. EA attenuated mechanical allodynia and anxiety-like behaviors in SNI mice, which may be associated with the activity of CaMKII neurons in the basolateral amygdala (BLA). Inhibition of BLACaMKII-rACC induced mechanical allodynia and anxiety-like behaviors in sham mice. Activation of the BLACaMKII-rACC alleviated neuropathic pain and anxiety-like behaviors in SNI mice. The analgesic and anxiolytic effects of 2 Hz EA were antagonized by the inhibition of the BLACaMKII-rACC. BLACaMKII-rACC mediates mechanical allodynia and anxiety-like behaviors. The analgesic and anxiolytic effects of 2 Hz EA may be associated with the BLACaMKII-rACC.

TEMPOROMANDIBULAR DISORDER, BODY PAIN, AND OTOLOGIC AND PSYCHOLOGIC SYMPTOMS: THEIR INTERRELATIONSHIPS IN ASIAN YOUTHS.

To establish the interrelationships between temporomandibular disorders (TMDs), pain, and otologic and psychologic comorbidities in Asian youths. Youths from a local polytechnic, aged 17 to 24 years old, were enrolled and an electronic survey encompassing demographic variables-the DC/TMD TMD pain screener (TPS), Short- form Fonseca Anamnestic Index (SFAI), modified Maciel's Otologic/Pain Symptom Inventory, and Patient Health Questionnaire-4-was administered. Par.cipants were subsequently categorized into groups: no TMD pain (NP), with TMD pain (WP), no TMDs (NT), and with any TMDs (WT). Data were evaluated with chi-square test, nonparametric, and logistic regression analyses (α &#61; .05). Among the 198 participants (mean age 18.8 ± 1.7 years), 11.1% had painful TMDs and 18.2% experienced TMD pain or dysfunction. Significant differences in total-otologic symptoms (total-OS), vertigo, and dizziness plus otalgia, tinnitus, and hearing loss scores were observed between the WP-NP and WT-NT groups correspondingly. While total-comorbid pain (total-CP) and psychologic distress (total-PD) scores varied substanally between the WT-NT group, only a significant difference in total-PD scores was discerned between the WP-NP group. Total-OS scores were moderately correlated to TPS/SFAI, total-CP, and total-PD scores, and psychologic distress was a risk factor for painful TMDs. Otologic and pain comorbidities were prevalent among Asian youths with TMDs and appear to be interrelated. The complex interaction of TMDs with pain, otologic, and psychologic comorbidities must be considered when caring for youths with multiple somatic complaints.