Comorbid Pain Research Articles

Lateral septum-lateral hypothalamus circuit dysfunction in comorbid pain and anxiety

Pain and anxiety comorbidities are a common health problem, but the neural mechanisms underlying comorbidity remain unclear. We propose that comorbidity implies that similar brain regions and neural circuits, with the lateral septum (LS) as a major candidate, process pain and anxiety. From results of behavioral and neurophysiological experiments combined with selective LS manipulation in mice, we find that LS GABAergic neurons were critical for both pain and anxiety. Selective activation of LS GABAergic neurons induced hyperalgesia and anxiety-like behaviors. In contrast, selective inhibition of LS GABAergic neurons reduced nocifensive withdrawal responses and anxiety-like behaviors. This was found in two mouse models, one for chronic inflammatory pain (induced by complete Freund’s adjuvant) and one for anxiety (induced by chronic restraint stress). Additionally, using TetTag chemogenetics to functionally mark LS neurons, we found that activation of LS neurons by acute pain stimulation could induce anxiety-like behaviors and vice versa. Furthermore, we show that LS GABAergic projection to the lateral hypothalamus (LH) plays an important role in the regulation of pain and anxiety comorbidities. Our study revealed that LS GABAergic neurons, and especially the LSGABAergic-LH circuit, are a critical to the modulation of pain and anxiety comorbidities.

Associations between Chronic Pain and Attention-Deficit Hyperactivity Disorder (ADHD) in Youth: A Scoping Review.

Background: Chronic pain and ADHD are common conditions among youth that negatively impact functioning. This review fills a critical gap by summarizing current research on chronic pain and ADHD comorbidity, and it proposes a conceptual model of shared associations and underlying mechanisms. Objective: The aims of the current study were to: (1) review the extant literature and present estimates of the prevalence of comorbid non-headache chronic pain and ADHD in youth and (2) describe potential shared mechanisms for ADHD and chronic non-headache pain in youth. We also outline future directions to inform future research and interventions directed to youth with comorbid pain and ADHD. Design: A scoping review of the literature was performed in MEDLINE, PsycInfo, and Cochrane Database of Systematic Reviews using a wide range of search terms related to pain, Attention Deficit-Hyperactivity Disorder, childhood, adolescence, and young adulthood. Results: Eleven published studies were included in the review. These studies examined the prevalence of chronic pain among youth with ADHD, the prevalence of ADHD in chronic pain samples, and the association between chronic pain and ADHD among youth. Findings revealed results from studies indicating a higher prevalence of ADHD among youth with chronic pain and a higher prevalence of chronic pain in samples of youth with ADHD. Conclusions: Findings from this scoping review suggest an association between chronic pain and ADHD among youth. Little research was found to examine the etiology of this association. Future studies should examine underlying mechanisms of comorbid chronic pain and ADHD.

The Growing Epidemic of Opioid Use Disorder in the Elderly and Its Treatment: A Review of the Literature.

Objective: US demographic trends show an increasing proportion of adults aged > 65 years old, approximately 1 million of whom are living with an opioid use disorder (OUD). OUD may be particularly problematic in this age group due to age-related pain syndromes and comorbidities that increase the risk of side effects, overdose, and death. The objective of this review was to assess the safety and efficacy of medications for OUD (MOUD) in the elderly.Data Sources: A systematic search of the literature in PubMed, CINAHL, MEDLINE, Embase, and Cochrane Library databases was conducted from January 1992 through October 2021. The following terms were used: elderly, older adults, opioid use disorder, opioid dependence, buprenorphine, methadone, and medication-assisted treatment.Study Selection: The search yielded 633 results. After following PRISMA guidelines and careful manual exclusion, 13 studies were selected for the review. No studies examining use of buprenorphine were identified for MOUD.Results: The application of methadone for MOUD in the elderly shows that use is limited by preexisting conditions such as cardiac conduction abnormalities, which are more prevalent in the elderly than in the general population. Buprenorphine and naltrexone have been documented to have fewer interactions and potentially lethal adverse effects compared to methadone.Conclusion: Future studies should focus on the application of buprenorphine or naltrexone for MOUD in the elderly.

Chronic pain conditions and risk of suicidal behavior: a 10-year longitudinal co-twin control study

BackgroundUnderstanding the relationship between chronic pain conditions and suicidal behavior—suicide attempt, other intentional self-harm, and death by suicide—is imperative for suicide prevention efforts. Although chronic pain conditions are associated with suicidal behaviors, these associations might be attributed to unmeasured confounding or mediated via pain comorbidity.MethodsWe linked a population-based Swedish twin study (N=17,148 twins) with 10 years of longitudinal, nationwide records of suicidal behavior from health and mortality registers through 2016. To investigate whether pain comorbidity versus specific pain conditions were more important for later suicidal behavior, we modeled a general factor of pain and two independent specific pain factors (measuring pain-related somatic symptoms and neck-shoulder pain, respectively) based on 9 self-reported chronic pain conditions. To examine whether the pain-suicidal behavior associations were attributable to familial confounding, we applied a co-twin control model.ResultsIndividuals scoring one standard deviation above the mean on the general pain factor had a 51% higher risk of experiencing suicidal behavior (odds ratio (OR), 1.51; 95% confidence interval (CI), 1.34–1.72). The specific factor of somatic pain was also associated with increased risk for suicidal behavior (OR, 1.80; 95% CI, 1.45–2.22]). However, after adjustment for familial confounding, the associations were greatly attenuated and not statistically significant within monozygotic twin pairs (general pain factor OR, 0.89; 95% CI, 0.59–1.33; somatic pain factor OR, 1.02; 95% CI, 0.49–2.11)ConclusionClinicians might benefit from measuring not only specific types of pain, but also pain comorbidity; however, treating pain might not necessarily reduce future suicidal behavior, as the associations appeared attributable to familial confounding.

Efficacy of Kampo medicine Kakkonto as acute medication to treat tension-type headache among musculoskeletal pain patients using regular analgesics.

Tension-type headache (TTH) is the most prevalent type of primary headache disorder. Its acute pharmacotherapy is acetaminophen or non-steroidal anti-inflammatory drugs based on the Japanese Clinical Practice Guideline for Headache Disorders 2021. With Japan's aging population, however, the number of TTH patients with comorbidities that have been treated by analgesics is increasing. Under this context, it is sometimes difficult to select an acute pharmacotherapy for TTH. Kakkonto, Japanese traditional herbal kampo medicine, is empirically used for TTH. We hypothesized that kakkonto has efficacy for TTH with painful comorbidities. We prospectively collected 10 consecutive TTH patients who had already taken analgesics for comorbidities. We prescribed 2.5g of kakkonto (TJ-1), and patients took it. A numerical rating scale for pain before and 2 hours after kakkonto intake was evaluated. Eight women and 2 men were included. The mean age was 71.0 ± 13.4 years old. Four patients had lower back pain, 2 had lumbar spinal stenosis, 2 had knee pain, 1 had neck pain, and 1 had shoulder myofasciitis. Celecoxib was used for 4 patients, acetaminophen for 3, loxoprofen for 2, and a combination of tramadol and acetaminophen for 1, as routinely used analgesics. The median numerical rating scale statistically improved from the median of 4 to that of 0. There were no side effects of kakkonto. Kakkonto showed efficacy as an acute medication for TTH with comorbidities that have been treated by analgesic.

Service use and costs in adolescents with pain and suicidality: across-sectional study.

Persistent/recurrent pain for more than three months and suicidality (suicide and self-harm related thoughts and behaviours) are serious and co-occurring health problems in adolescence, underscoring the need for targeted support. However, little is known about service use and costs in adolescents with pain-suicidality comorbidity, compared to those with either problem alone. This study aimed to shed light on service use and costs in adolescents with pain and/or suicidality, and the role of individual and school characteristics. We analysed cross-sectional, pre-intervention data from a large cluster randomised controlled trial, collected between 2017 and 2019 on a representative sample of 8072 adolescents (55% female; aged 11-15 years; 76% white) in 84 schools in the UK. We explored service use settings, covering health, social, educational settings, and medication for mental health problems over three months. Data were analysed using descriptive statistics and two-part hurdle models to obtain odds ratios (ORs) and incident rate ratios (IRRs). 9% of adolescents reported comorbidity between pain and suicidality, 11% only suicidality, 13% only pain, and 66% neither pain nor suicidality. Approximately 55% of adolescents used services, especially general practitioner visits, outpatient appointments for injuries and contacts with a school nurse or pharmacist. Compared to adolescents with neither pain nor suicidality: (i) adolescents with pain (OR 3.79, 95% CI 2.63-5.48), suicidality (1.68, 1.12-2.51), and pain-suicidality comorbidity (2.35, 1.26-4.41) were more likely to use services and (ii) if services were used, they were more likely to have higher total costs (Pain: IRR 1.25, 95% CI 1.11-1.42; Suicidality: 1.27, 1.11-1.46; Comorbidity: 1.57, 1.34-1.85). In our study, adolescents with pain and suicidality reported increased contact with health, social, and educational services, which could provide an opportunity for suicide prevention. Given the diversity of identified settings, multi-sector suicide prevention strategies are paramount. Wellcome Trust [WT104908/Z/14/Z; WT107496/Z/15/Z]; Stiftung Oskar-Helene-Heim.

Ketamine in chronic pain

Ketamine is now frequently used in the management of chronic pain refractory to conventional treatments. However, its efficacy and adverse effects appear variable in the literature in line with heterogeneous methodologies and modes of administration, leading to controversy regarding the actual interest of ketamine for chronic pain treatment. A need for clinical trials on larger cohorts of well selected patients but also real-life studies to more accurately quantify its efficacy, refine its prescription dosages and better understand its long-term adverse effects is highlighted in the literature. Progress in this direction has been achieved in recent years with improved recommendations for use, taking into account different trajectories of analgesia with ketamine, depending on the etiology of the pain, and the psycho-affective profile of patients. A holistic approach is clearly needed with consideration of pain and depression comorbidities to optimize pain management.

The Experience of BIPOC Living with Chronic Pain in the USA: Biopsychosocial Factors that Underlie Racial Disparities in Pain Outcomes, Comorbidities, Inequities, and Barriers to Treatment.

This review synthesizes recent findings related to the biopsychosocial processes that underlie racial disparities in chronic pain, while highlighting opportunities for interventions to reduce disparities in pain treatment among BIPOC. Chronic pain is a prevalent and costly public health concern that disproportionately burdens Black, Indigenous, and people of color (BIPOC). This unequal burden arises from an interplay among biological, psychological, and social factors. Social determinants of health (e.g., income, education level, and lack of access or inability to utilize healthcare services) are known to affect overall health, including chronic pain, and disproportionately affect BIPOC communities. This burden is exacerbated by exposure to psychosocial stressors (i.e., perceived injustice, discrimination, and race-based traumatic stress) and can affect biological systems that modulate pain (i.e., inflammation and pain epigenetics). Further, there are racial/ethnic disparities in pain treatment, perpetuating the cycle of undermanaged chronic pain among BIPOC.

Role of 5-HT1A-mediated upregulation of brain indoleamine 2,3 dioxygenase 1 in the reduced antidepressant and antihyperalgesic effects of fluoxetine during maintenance treatment.

The reduced antidepressant and antihyperalgesic effects of selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine during maintenance treatment has been reported, but little is known about the molecular mechanism of this phenomenon. In three comorbid pain and depression animal models (genetic predisposition, chronic social stress, arthritis), we showed that the fluoxetine's antidepressant and antihyperalgesic effects were reduced during the maintenance treatment. Fluoxetine exposure induced upregulation of the 5-hydroxytryptamine 1A (5-HT1A) auto-receptor and indoleamine 2,3 dioxygenase 1 (IDO1, a rate-limiting enzyme of tryptophan metabolism) in the brainstem dorsal raphe nucleus (DRN), which shifted the tryptophan metabolism away from the 5-HT biosynthesis. Mechanistically, IDO1 upregulation was downstream to fluoxetine-induced 5-HT1A receptor expression because 1) antagonism of the 5-HT1A receptor with WAY100635 or 5-HT1A receptor knockout blocked the IDO1 upregulation, and 2) inhibition of IDO1 activity did not block the 5-HT1A receptor upregulation following fluoxetine exposure. Importantly, inhibition of either the 5-HT1A receptor or IDO1 activity sustained the fluoxetine's antidepressant and antihyperalgesic effects, indicating that 5-HT1A-mediated IDO1 upregulation in the brainstem DRN contributed to the reduced antidepressant and antihyperalgesic effects of fluoxetine. These results suggest a new strategy to improving the therapeutic efficacy of SSRI during maintenance treatment.

Medio-dorsal thalamic dysconnectivity in chronic knee pain: A possible mechanism for negative affect and pain comorbidity.

The reciprocal interaction between pain and negative affect is acknowledged but pain-related alterations in brain circuits involved in this interaction, such as the mediodorsal thalamus (MDThal), still require a better understanding. We sought to investigate the relationship between MDThal circuitry, negative affect and pain severity in chronic musculoskeletal pain. For these analyses, participants with chronic knee pain (CKP, n = 74) and without (n = 36) completed magnetic resonance imaging scans and questionnaires. Seed-based MDThal functional connectivity (FC) was compared between groups. Within CKP group, we assessed the interdependence of MDThal FC with negative affect. Finally, post hoc moderation analysis explored whether burden of pain influences affect-related MDThal FC. The CKP group showed altered MDThal FC to hippocampus, ventromedial prefrontal cortex and subgenual anterior cingulate. Furthermore, in CKP group, MDThal connectivity correlated significantly with negative affect in several brain regions, most notably the medial prefrontal cortex, and this association was stronger with increasing pain burden and absent in pain-free controls. In conclusion, we demonstrate mediodorsal thalamo-cortical dysconnectivity in chronic pain with areas linked to mood disorders and associations of MDThal FC with negative affect. Moreover, burden of pain seems to enhance affect sensitivity of MDThal FC. These findings suggest mediodorsal thalamic network changes as possible drivers of the detrimental interplay between chronic pain and negative affect.

Chronic low back pain comorbidity count and its impact on exacerbating opioid and non-opioid prescribing behavior.

The objective of the study was to determine the characteristics of chronic low back pain (CLBP) comorbidity and its impact on opioid and non-opioid treatments among Chicagoland patients with CLBP. A retrospective cross-sectional study comparing differences in comorbidity and treatment patterns among Chicagoland patients with CLBP against a matched control arm without chronic low back pain (NCLBP). Academic hospital system outpatient services. Using the International Classification of Diseases, 10th Revision codes (ICD 10) 9589 patients were identified with CLBP with a median age of 57 years old and 62.32% female distribution. The NCLBP group comprised 9589 age-, sex-, race-, and region-matched patients. An increased prevalence across all 17 studied comorbidities was found in CLBP patients as compared to NCLBP patients. CLBP patients carried an average of 3.5 comorbidities compared with 2.4 comorbidities in NCLBP patients. Rheumatoid arthritis (RA), joint arthritis, and obesity had the strongest relationship with CLBP. Additionally, we found that the most prescribed treatment for CLBP were opioids, which ranked above NSAIDs and physical therapy. 56% of CLBP patients were prescribed opioids as compared to 36% of NCLBP patients (Odds Ratio=2.28, 95% CI: 2.16-2.42). Tramadol was the agent with the strongest relationship to CLBP. CLBP patients were more likely to use two or more opioids concomitantly. The number of total treatments was positively associated with the number of comorbidities in both CLBP and NCLBP patients (Cochran-Armitage trend test p < 0.0001). Chronic low back pain patients showed a higher number of comorbidities than their NCLBP counterparts. Comorbidity count trended positively with higher treatment burden with opioids being the most prescribed treatment, often with poly-opioid use, over conservative modalities such as NSAIDs and physical therapy.

Characterizing the burden of calciphylaxis: a qualitative analysis.

Calciphylaxis is a debilitating disease associated with high mortality and morbidity secondary to pain, nonhealing wounds and frequent hospital admissions. We qualitatively assessed the burden of calciphylaxis on patient quality of life through semi-structured interviews with nine adult participants. Participants identified an inability to complete activities of daily living because of mobility impairment and decreased strength, although most denied complete dependence on others. All participants described pain as the worst aspect of disease, citing a variable course, unpredictability in severity and poor control despite medical therapy. Calciphylaxis also caused feelings of sadness and anger, having a negative impact on self-confidence. Supportive care needs to address the pervasive and severe nature of pain, mobility impairment and psychiatric comorbidities; such interventions may decrease the overall burden for patients with calciphylaxis.

Effects of a trauma-informed mindful recovery program on comorbid pain, anxiety, and substance use during primary care buprenorphine treatment: A proof-of-concept study.

A mindfulness-based intervention that reduces comorbid pain, anxiety, and substance use during office-based opioid treatment (OBOT) could enhance retention and prevent overdose. We conducted a pilot study of the Mindful Recovery OUD Care Continuum (M-ROCC), a 24-week trauma-informed program with a motivationally-sensitive curriculum. Patients prescribed buprenorphine (N = 18) enrolled in M-ROCC. We collected urine toxicology biweekly. At 0, 4, and 24 weeks, participants completed PROMIS-Pain, PROMIS-Anxiety, Mindfulness (FFMQ), Experiential Avoidance (BEAQ), Interoceptive Awareness (MAIA), and Self-Compassion (SCS-SF) scales. We estimated changes over time using mixed models. Participants completed qualitative interviews at 4 and 24 weeks. Positive urine toxicology decreased over time for cocaine (β = -.266, p = .008) and benzodiazepines (β = -.208, p = .028). M-ROCC reduced PROMIS-Pain (Z = -2.29; p = .022), BEAQ (Z = -2.83; p = .0005), and increased FFMQ (Z = 3.51; p < .001), MAIA (Z = 3.40; p = .001), and SCS-SF (Z = 2.29; p = .022). Participants with co-morbid anxiety had decreased PROMIS-Anxiety (Z = -2.53; p = .012). Interviewed participants commonly used mindfulness practices for stress and anxiety (12/12, 100%), and to reduce pain catastrophizing and rumination (7/12, 58%). This is the first study to report the effects of a 24-week mindfulness program during buprenorphine treatment on common comorbidities, including pain interference, anxiety, cocaine, and benzodiazepine use. The findings that M-ROCC is associated with reduced experiential avoidance, as well as increased interoceptive awareness and self-compassion, align with proposed mechanisms that are now extended to OUD treatment. Future larger randomized controlled trials are needed before effectiveness can be established and the role of these mechanisms can be confirmed.

Efficacy of Computerized Visual Tracking Technology Throughout Concussion Recovery: A Case Series

<h3>Research Objectives</h3> To compare results of computerized eye tracking assessments to concussion patient reported outcomes and other objective oculomotor function tests throughout the concussion recovery. <h3>Design</h3> Retrospective case series of three physical therapy plan of cares completed between April 2021 and September 2021. <h3>Setting</h3> Outpatient physical rehabilitation clinic. <h3>Participants</h3> Included three female patients (mean age 34.7 years). Brain injury conditions vary from sub-acute to chronic. Selected via volunteer sample. <h3>Interventions</h3> Manual therapy, postural stabilization, aerobic conditioning, ocular motor training, and balance exercises. Average physical therapy visit count of 15.3. <h3>Main Outcome Measures</h3> RightEye™ Dynamic Visual Acuity (DVA) Test, Concussion Clinical Profile Screen (CCPS), Clinical DVA, Somatosensory Organization Test (SOT), and Vestibular Ocular Motor Screen (VOMS). <h3>Results</h3> All final RightEye™ DVA composite scores declined or had minimal change compared to evaluation scores. Initial VOMS similar findings to initial RightEye™ DVA subdomain scores. CCPS composite and ocular profile scores improved with each re-assessment. Clinical DVA scores improved and within normal limits at final assessments. 2/3 of participants had normal composite scores on SOT at re-evaluation. <h3>Conclusions</h3> In this case series subjective recovery of concussion symptoms did not correlate with performance on computerized ocular motor assessments. There were conflicting results on several other objective tests compared to results of RightEye™ DVA. Some confounding factors that may have impacted scores are co-morbidities of cervical pain, anxiety, depression, and migraine. Even though the assessments did not correlate, it is important to note the tracking assessments and games were engaging and offered repetition. In conclusion, clinicians should not rely on one single measurement for concussion screening and determination of readiness for return to prior activities. More research is needed to determine the efficacy of computerized visual tracking assessments for individuals with complex medical history and post-concussion. <h3>Author(s) Disclosures</h3> The author has nothing to disclose.

Long-term Use of Wearable Health Technology by Chronic Pain Patients.

People living with chronic pain may use wearable health technology (WHT) in conjunction with an expert-directed pain management program for up to 1 year. WHT use may be associated with improvements in key patient outcomes. A 12-month study of WHT use among people with chronic pain was conducted, consisting of iPhone and Apple Watch applications to measure movement, sleep, and self-reported pain. Clinical outcomes among 105 patients enrolled in a multidisciplinary pain program that included WHT use were compared with 146 patients in the same program but without WHT, and to 161 patients receiving medical pain management without WHT. Participants used the WHT on average 143.0 (SD: 117.6) out of 365 days. Mixed-effects models revealed participants who used WHT had decreases in depression scores (-7.83, P <0.01) and prescribed morphine milligram equivalents (-21.55, P =0.04) over 1 year. Control groups also showed decreases in depression scores (-5.08, P =0.01; -5.68, P <0.01) and morphine milligram equivalents (-18.67, P =0.01; -10.99, ns). The estimated slope of change among the WHT was not statistically different than control groups. Patients who used WHT as part of their pain management program demonstrated a willingness to do so for extended periods of time despite living with chronic pain and other comorbidities. Data trends suggest that WHT use may positively impact depression and prescribed medication. Additional research is warranted to investigate the potential of WHT to improve the negative consequences of chronic pain.

The prevalence of fibromyalgia among doctors in the tertiary care hospital: A cross-sectional study.

Fibromyalgia syndrome (FMS) is an umbrella term for chronic pain syndrome, associated with tenderness, fatigue, reduced pain thresholds, and paresthesia in the limbs. The field of medicine places doctors in constant work-related stress, sleep deprivation, and depression, thus increasing their vulnerability to developing FMS. This study aims to evaluate the prevalence and severity of FM (fibromyalgia) among physicians in a tertiary care hospital setting. The cross-sectional study was performed at the Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from December 2019 to December 2020.243 physicians of either gender, and from all the departments being house officers, medical officers, and post-graduate trainees were included & divided into 3 age groups from 20 to more than 45 years. Widespread Pain Index (WPI) equal to or more than 7 and Symptom Severity Score (SSS) equal to or more than 5 OR WPI=3 to 6 and SSS equal to or more than 9 were required, according to the modified American College of Rheumatology preliminary diagnostic criteria 2016 for fibromyalgia diagnosis. Data was analyzed using SPSS 25. Among a total of 243 participants, FMS was diagnosed in 69 (28.40%) individuals. The predominant FMS population was the youngest age group 20-35 (56=81.16%). Increased BMI, increasing pain score category, gender, and comorbidities are significantly associated with FMS (p≤0.05). Whereas, advancing age is insignificantly linked with FMS (p>0.05). The prevalence of fibromyalgia was found to be high among doctors working in stressful hospital settings, particularly among the youngest ones.

Investigating the shared genetic architecture and causal relationship between pain and neuropsychiatric disorders.

Pain often occurs in parallel with neuropsychiatric disorders. However, the underlying mechanisms and potential causality have not been well studied. We collected the genome-wide association study (GWAS) summary statistics of 26 common pain and neuropsychiatric disorders with sample size ranging from 17,310 to 482,730 in European population. The genetic correlation between pair of pain and neuropsychiatric disorders, as well as the relevant cell types were investigated by linkage disequilibrium (LD) score regression analyses. Then, transcriptome-wide association study (TWAS) was applied to identify the potential shared genes by integrating the gene expression information and GWAS. In addition, Mendelian randomization (MR) analyses were conducted to infer the potential causality between pain and neuropsychiatric disorders. Among the 169 pairwise pain and neuropsychiatric disorders, 55 pairs showed positive correlations (median rg = 0.43) and 9 pairs showed negative correlations (median rg = -0.31). Using MR analyses, 26 likely causal associations were identified, including that neuroticism and insomnia were risk factors for most of short-term pain, and multisite chronic pain was risk factor for neuroticism, insomnia, major depressive disorder and attention deficit/hyperactivity disorder, and vice versa. The signals of pain and neuropsychiatric disorders tended to be enriched in the functional regions of cell types from central nervous system (CNS). A total of 19 genes shared in at least one pain and neuropsychiatric disorder pair were identified by TWAS, including AMT, NCOA6, and UNC45A, which involved in glycine degradation, insulin secretion, and cell proliferation, respectively. Our findings provided the evidence of shared genetic structure, causality and potential shared pathogenic mechanisms between pain and neuropsychiatric disorders, and enhanced our understanding of the comorbidities of pain and neuropsychiatric disorders.

Desulfovibrio confers resilience to the comorbidity of pain and anxiety in a mouse model of chronic inflammatory pain.

Patients with chronic pain frequently suffer from anxiety symptoms. It has been well established that gut microbiota is associated with the pathogenesis of pain and anxiety. However, it is unknown whether the gut microbiota, particularly the specific bacteria, play a role in the comorbidity of chronic pain and anxiety. Chronic inflammatory pain was induced in mice by a single injection of complete Freund's adjuvant (CFA). Mice were then separated into anxiety-susceptible and anxiety-resilient phenotypes by hierarchical clustering analysis of behaviors. Fecal samples were collected to perform 16S rRNA gene sequencing. Chronic diazepam intervention served as a therapeutic strategy and its effect on the composition of gut microbiota was also determined. α-Diversity and β-diversity both showed significant differences among the groups. A total of 12 gut bacteria were both altered after CFA injection and reversed by chronic diazepam treatment. More importantly, the pain hypersensitivity and anxiety-like behaviors were relieved by chronic diazepam treatment. Interestingly, we also found that Desulfovibrio was increased in anxiety-resilient group compared to control and anxiety-susceptible groups. Abnormal composition of gut microbiota plays an essential role in chronic pain as well as in anxiety. Besides, the increased level of Desulfovibrio in anxiety-resilient mice indicated its therapeutic effects on the comorbidity of pain and anxiety. Collectively, targeting gut microbiota, especially increasing the Desulfovibrio level, might be effective in the alleviation of chronic pain-anxiety comorbidity.

Self-Reported Mandibular Impairment and Cervical Pain Comorbidity in Undergraduate Dental Students

The aim of this study was to evaluate the frequency of co-existence of self-reported mandibular functional impairment and cervical pain in the same individuals. Participants answered a validated Mandibular Functional Impairment Questionnaire (MFIQ) and also indicated in a schematic map the region of cervical pain when it was reported. The frequency of cervical pain in participants with or without mandibular functional was compared with Chi-squared test. The final evaluated population consisted of 80 participants, 28 men (35%) and 52 women (65%), with ages ranging between 18 and 55 years (median = 20). It was found that 43.75% (n = 35) reported cervical pain, 15% of participants reported some degree of mandibular impairment, and 11.25% presented the comorbidity. In conclusion, participants with mandibular impairment presented significantly more frequent cervical pain than participants without mandibular impairment.

MDMA-assisted therapy is associated with a reduction in chronic pain among people with post-traumatic stress disorder

Increasing evidence demonstrates 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy (MDMA-AT) may be a safe and effective treatment for post-traumatic stress disorder (PTSD). There is growing interest in MDMA-AT to address a range of other health challenges. Chronic pain and PTSD are frequently comorbid, reciprocally interdependent conditions, though the possible role of MDMA-AT in treating chronic pain remains under-investigated. The present analysis examined the impact of manualized MDMA-AT on chronic pain severity among participants with PTSD who were enrolled in a Phase 2 clinical trial investigating MDMA-AT for PTSD (NCT03282123). Exploratory data from a subset of participants who completed chronic pain measures (n = 32) were drawn from a Phase 2 open-label study sponsored by the Multidisciplinary Association for Psychedelic Studies (MAPS). Multivariable analysis of variance (ANOVA) was utilized to compare pre- vs. post-treatment Chronic Pain Grade Scale (CPGS) values, adjusting for demographics (age, sex, and ethnicity). K-means clustering was then used to group the sample into three clusters to denote high (n = 9), medium (n = 11), and low (n = 12) baseline pain severity, and the same analysis was repeated for each cluster. Among the 32 participants included in this analysis, 59% (n = 19) were women, 72% (n = 23) were white, and median age was 38 years [interquartile range (IQR) = 31-47]. Overall, 84% (n = 27) reported having pain, and 75% (n = 24) reported disability associated with their pain. Significant reductions in CPGS subscales for pain intensity and disability score, and overall CPGS severity grade were observed among participants in the highest pain cluster (n = 9, p < 0.05), and for pain intensity in the medium pain cluster (n = 11, p < 0.05) post- vs. pre-treatment. Findings demonstrate a high prevalence of chronic pain in this sample of people with severe PTSD and that chronic pain scores among medium and high pain subgroups were significantly lower following MDMA-AT. While these data are preliminary, when considered alongside the frequency of comorbid chronic pain and PTSD and promising efficacy of MDMA-AT for treating PTSD, these findings encourage further research exploring the role of MDMA-AT for chronic pain.