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Purpose Several chronic pain conditions may be distinguished by condition specific brain anatomical and functional abnormalities on imaging, which are suggestive of underlying disease processes. We present what is to our knowledge the first characterization of interstitial cystitis/bladder pain syndrome associated white matter (axonal) abnormalities based on multicenter neuroimaging from the MAPP Research Network. Materials and Methods We assessed 34 women with interstitial cystitis/bladder pain syndrome and 32 healthy controls using questionnaires on pain, mood and daily function. White matter microstructure was evaluated by diffusion tensor imaging to model directional water flow along axons or fractional anisotropy. Regions correlating with clinical parameters were further examined for gender and syndrome dependence. Results Women with interstitial cystitis/bladder pain syndrome showed numerous white matter abnormalities that correlated with pain severity, urinary symptoms and impaired quality of life. Interstitial cystitis/bladder pain syndrome was characterized by decreased fractional anisotropy in aspects of the right anterior thalamic radiation, the left forceps major and the right longitudinal fasciculus. Increased fractional anisotropy was detected in the right superior and bilateral inferior longitudinal fasciculi. Conclusions To our knowledge we report the first characterization of brain white matter abnormalities in women with interstitial cystitis/bladder pain syndrome. Regional decreases and increases in white matter integrity across multiple axonal tracts were associated with symptom severity. Given that white matter abnormalities closely correlated with hallmark symptoms of interstitial cystitis/bladder pain syndrome, including bladder pain and urinary symptoms, brain anatomical alterations suggest that there are neuropathological contributions to chronic urological pelvic pain.

J Ryan Scott,1 Afton L Hassett,1 Chad M Brummett,1 Richard E Harris,1,2 Daniel J Clauw,1,2 Steven E Harte1,2 1Chronic Pain and Fatigue Research Center, Department of Anesthesiology, 2Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA Background: Caffeine’s properties as an analgesic adjuvant with nonsteroidal anti-inflammatory drugs/acetaminophen are well documented. However, little clinical research has explored ca­ffeine’s effects on opioid analgesia. This study assessed the effects of caffeine consumption on pain and other symptoms in opioid-using and nonusing chronic pain patients meeting the survey criteria for fibromyalgia. Materials and methods: Patients presenting to a university-based pain clinic completed validated self-report questionnaires assessing symptoms. Patients (N=962) meeting the fibromyalgia survey criteria were stratified by opioid use and further split into groups based on caffeine amount consumed per day (no caffeine, or low, moderate, high caffeine). Analysis of covariance with Dunnett’s post hoc testing compared pain and symptom severity between the no caffeine group and the caffeine consuming groups. Results: In opioid users, caffeine consumption had modest but significant effects on pain, catastrophizing, and physical function. Lower levels of pain interference were associated with low and moderate caffeine use compared to no caffeine intake. Lower pain catastrophizing and higher physical function were observed in all caffeine dose groups, relative to the no caffeine group. Lower pain severity and depression were observed only in the moderate caffeine group. In opioid nonusers, low caffeine intake was associated with higher physical function; however, no other significant effects were observed. Conclusion: Caffeine consumption was associated with decreased pain and symptom severity in opioid users, but not in opioid nonusers, indicating caffeine may act as an opioid adjuvant in fibromyalgia-like chronic pain patients. These data suggest that caffeine consumption concomitant with opioid analgesics could provide therapeutic benefits not seen with opioids or caffeine alone. Keywords: caffeine, fibromyalgia, opioid analgesics, pain, analgesic adjuvant, chronic pain

Cynthia J Schoen,1,* Jacob N Ablin,2,* Eric Ichesco,1 Rupal J Bhavsar,3 Laura Kochlefl,1 Richard E Harris,1 Daniel J Clauw,1 Richard H Gracely,4 Steven E Harte1 1Department of Anesthesiology, Chronic Pain and Fatigue Research Center, University of Michigan, Ann Arbor, MI, USA; 2Institute of Rheumatology, Tel Aviv Suorasky Medical Center, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 3Department of Neurology, University of Pennsylvania, Philadelphia, PA, 4Department of Endodontics, University of North Carolina – Chapel Hill, Chapel Hill, NC, USA *These authors contributed equally to this work Introduction: Application of noxious stimulation to one body area reduces pain sensitivity in a remote body area through activation of an endogenous pain-inhibitory network, a behavioral phenomenon referred to as conditioned pain modulation (CPM). The efficiency of CPM is predictive of a variety of health outcomes, while impaired CPM has been associated with various chronic pain conditions. Current methods used to assess CPM vary widely, and interest in CPM method development remains strong. Here, we evaluated a novel method for assessing CPM in healthy controls and fibromyalgia (FM) patients using thumb pressure as both a test and conditioning stimulus.Methods: Sixteen female FM patients and 14 matched healthy controls underwent CPM testing with thumbnail pressure as the test stimulus, and either cold water or noxious pressure as the conditioning stimulus. CPM magnitude was evaluated as the difference in pain rating of the test stimulus applied before and during the conditioning stimulus.Results: In healthy controls, application of either pressure or cold water conditioning stimulation induced CPM as evidenced by a significant reduction in test stimulus pain rating during conditioning (P=0.007 and P=0.021, respectively). In contrast, in FM patients, neither conditioning stimulus induced a significant CPM effect P-values >0.274). There was a significant difference in CPM magnitude for FM patients compared to healthy controls with noxious pressure conditioning stimulation (P=0.023); however, no significant difference in CPM was found between groups using cold water as a conditioning stimulus (P=0.269).Conclusion: The current study demonstrates that thumbnail pressure can be used as both a test and conditioning stimulus in the assessment of CPM. This study further confirms previous findings of attenuated CPM in FM patients compared with healthy controls. Keywords: pressure pain, cold pressor test, diffuse noxious inhibitory controls, quantitative sensory testing

Philip J Mease,1 Daniel J Clauw,2 Joel M Trugman,3 Robert H Palmer,3 Yong Wang3 1Swedish Medical Center and University of Washington, Seattle, WA, USA; 2Chronic Pain and Fatigue Research Center, University of Michigan Health System, Ann Arbor, MI, USA; 3Forest Research Institute, Jersey City, NJ, USA Background: Fibromyalgia patients from a long-term, open-label study of milnacipran (50–200 mg/day) were eligible to participate in a 12-week, randomized, placebo-controlled withdrawal study. The withdrawal study evaluated loss of therapeutic response in patients who achieved ≥50% pain improvements after receiving up to 3.25 years of milnacipran. This post-hoc analysis investigated whether patients who met lower thresholds of pain improvement also experienced worsening of fibromyalgia symptoms upon treatment withdrawal. Method: Among patients who received milnacipran ≥100 mg/day during the long-term study, three subgroups were identified based on percentage of pain reduction at randomization: ≥50% (protocol-defined "responders"; n=150); ≥30% to

Fibromyalgia (FM) is a common chronic widespread pain disorder. Our understanding of FM has increased substantially in recent years with extensive research suggesting a neurogenic origin for the most prominent symptom of FM, chronic widespread pain. Neurochemical imbalances in the central nervous system are associated with central amplification of pain perception characterized by allodynia (a heightened sensitivity to stimuli that are not normally painful) and hyperalgesia (an increased response to painful stimuli). Despite this increased awareness and understanding, FM remains undiagnosed in an estimated 75% of people with the disorder. Clinicians could more effectively diagnose and manage FM if they better understood its underlying mechanisms. Fibromyalgia is a disorder of pain processing. Evidence suggests that both the ascending and descending pain pathways operate abnormally, resulting in central amplification of pain signals, analogous to the "volume control setting" being turned up too high. Patients with FM also exhibit changes in the levels of neurotransmitters that cause augmented central nervous system pain processing; levels of several neurotransmitters that facilitate pain transmission are elevated in the cerebrospinal fluid and brain, and levels of several neurotransmitters known to inhibit pain transmission are decreased. Pharmacological agents that act centrally in ascending and/or descending pain processing pathways, such as medications with approved indications for FM, are effective in many patients with FM as well as other conditions involving central pain amplification. Research is ongoing to determine the role of analogous central nervous system factors in the other cardinal symptoms of FM, such as fatigue, nonrestorative sleep, and cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Fibromyalgia (FM) is a chronic widespread pain disorder often seen in primary care practices. Advances in the understanding of FM pathophysiology and clinical presentation have improved the recognition and diagnosis of FM in clinical practice. Fibromyalgia is a clinical diagnosis based on signs and symptoms and is appropriate for primary care practitioners to make. The hallmark symptoms used to identify FM are chronic widespread pain, fatigue, and sleep disturbances. Awareness of common mimics of FM and comorbid disorders will increase confidence in establishing a diagnosis of FM. [ABSTRACT FROM AUTHOR]

BACKGROUND: Preclinical and clinical studies have suggested that milnacipran, a dual norepinephrine-serotonin reuptake inhibitor, may be efficacious in the treatment of fibromyalgia (FM). OBJECTIVE: This study was conducted to evaluate the efficacy and tolerability of milnacipran in treating the multiple domains of FM. METHODS: This was a multicenter, double-blind, placebo-controlled trial. Adult patients (age 18-70 years) who met 1990 American College of Rheumatology criteria for FM were randomized to receive milnacipran 100 mg/d, milnacipran 200 mg/d, or placebo for 15 weeks. Because this was a pivotal registration trial, the primary end points were chosen to investigate efficacy for 2 potential indications: the treatment of FM and the treatment of FM pain. Thus, the 2 primary efficacy end points were rates of FM composite responders and FM pain composite responders. FM composite responders were defined as patients concurrently experiencing clinically meaningful improvements in the following 3 domain criteria: pain (> or = 30% improvement, as recorded in an electronic diary); patients' global status (a rating of very much improved or much improved on the Patient Global Impression of Change [PGIC] scale); and physical function (a > or = 6-point improvement on the 36-item Short-Form Health Survey [SF-36] Physical Component Summary score). FM pain composite responders were defined as those who met the pain and PGIC criteria. Adverse events reported by patients or observed by investigators were recorded throughout the trial. RESULTS: Of 2270 patients screened, 1196 were randomized to receive milnacipran 100 mg/d (n = 399), milnacipran 200 mg/d (n = 396), or placebo (n = 401). The majority of patients were female (96.2%) and white (93.5%). The population had a mean age of 50.2 years, a mean baseline weight of 180.8 pounds, and a mean baseline body mass index of 30.6 kg/m(2). Compared with placebo, significantly greater proportions of milnacipran-treated patients were FM composite responders (100 mg/d: P = 0.01; 200 mg/d: P = 0.02) and FM pain composite responders (100 mg/d: P = 0.03; 200 mg/d: P = 0.004). Milnacipran was associated with significant improvements in pain after 1 week of treatment (100 mg/d: P = 0.004; 200 mg/d: P = 0.04), as well as significant improvements in multiple secondary efficacy end points, including global status (PGIC: P<0.001 for both doses), physical function (SF-36 physical functioning domain-100 mg/d: P < 0.001; 200 mg/d: P = 0.02), and fatigue (Multidimensional Fatigue Inventory- 100 mg/d: P = 0.04). The most commonly reported adverse events with milnacipran were nausea (100 mg/d, 34.3%; 200 mg/d, 37.6%), headache (18.0% and 17.7%, respectively), and constipation (14.3% and 17.9%). Adverse events resulted in premature study discontinuation in 19.5% and 23.7% of those who received milnacipran 100 and 200 mg/d, respectively, compared with 9.5% of placebo recipients. CONCLUSION: In these adult patients with FM, both doses of milnacipran (100 and 200 mg/d) were associated with significant improvements in pain and other symptoms. Clinical Trials Identification Number: NCT00098124. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Bisphosphonates have slowed the progression of osteoarthritis (OA) in animal models and have decreased pain in states of high bone turnover. The Knee OA Structural Arthritis (KOSTAR) study, which is the largest study to date investigating a potential structure-modifying OA drug, tested the efficacy of risedronate in providing symptom relief and slowing disease progression in patients with knee OA. METHODS: The study group comprised 2,483 patients with medial compartment knee OA and 2-4 mm of joint space width (JSW), as determined using fluoroscopically positioned, semiflexed-view radiography. Patients were enrolled in 2 parallel 2-year studies in North America and the European Union. These studies evaluated the efficacy of risedronate at dosages of 5 mg/day, 15 mg/day, 35 mg/week (in Europe), and 50 mg/week (in North America) compared with placebo in reducing signs and symptoms, as measured by the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and patient global assessment (PGA) scores, and in slowing radiographic progression. RESULTS: A reduction of approximately 20% in signs and symptoms, as measured by WOMAC subscales and PGA scores, was observed in all groups, with no treatment effect of risedronate demonstrated. Risedronate did not significantly reduce radiographic progression as measured by decreased JSW or using a dichotomous definition of progression (joint space loss of >or=0.6 mm). Thirteen percent of patients receiving placebo demonstrated significant disease progression over 2 years. A dose-dependent reduction in the level of C-terminal crosslinking telopeptide of type II collagen, a cartilage degradation marker associated with progressive OA, was seen in patients who received risedronate. No increase in the number of adverse events was demonstrated for risedronate compared with placebo. CONCLUSION: Although risedronate (compared with placebo) did not improve signs or symptoms of OA, nor did it alter progression of OA, a reduction in the level of a marker of cartilage degradation was observed. A sustained clinically relevant improvement in signs and symptoms was observed in all treatment and placebo groups. [ABSTRACT FROM AUTHOR]

Varying practitioner beliefs about what makes patients who have fibromyalgia syndrome (FMS) 'behave' differently from the general population are complicated by a paucity of studies, heterogeneity of the patient population, and other factors. The most common psychological conditions associated with FMS are generalized anxiety disorder, post-traumatic stress disorder, somatization, and mood disorders. Psychological conditions that are not associated with FMS often are confused with it and need to be ruled out. The Multidimensional Pain Inventory and other screening measures may help identify psychological disturbances that can exacerbate physical conditions and symptoms. Rehabilitation may consist of an interdisciplinary treatment program that includes medication education, aerobic and stretching exercises, and pacing activities and body ergonomics. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To compare the momentary association between salivary cortisol levels and pain, fatigue, and stress symptoms in patients with fibromyalgia (FM), and to compare diurnal cycles of cortisol secretion in patients with FM and healthy control subjects in a naturalistic environment. METHODS: Twenty-eight patients with FM and 27 healthy control subjects completed assessments on salivary cortisol levels and pain, fatigue, and stress symptoms, 5 times a day for 2 consecutive days, while engaging in usual daily activities. Only those participants who adhered to the protocol (assessed via activity monitor) were included in the final analyses. RESULTS: Twenty FM patients and 16 healthy control subjects adhered to the protocol. There were no significant differences in cortisol levels or diurnal cortisol variation between FM patients and healthy controls. Among women with FM, a strong relationship between cortisol level and current pain symptoms was observed at the waking time point (t = 3.35, P = 0.008) and 1 hour after waking (t = 2.97, P = 0.011), but not at the later 3 time points. This association was not due to differences in age, number of symptoms of depression, or self-reported history of physical or sexual abuse. Cortisol levels alone explained 38% and 14% of the variation in pain at the waking and 1 hour time points, respectively. No relationship was observed between cortisol level and fatigue or stress symptoms at any of the 5 time points. CONCLUSION: Among women with FM, pain symptoms early in the day are associated with variations in function of the hypothalamic-pituitary-adrenal axis. [ABSTRACT FROM AUTHOR]

Purpose. Fibromyalgia (FM) and chronic widespread pain (CWP) are common, but the etiology of these disorders remains poorly understood. A large body of data indicates a neurobiological basis for these disorders, but this information has not been effectively transmitted to many medical professionals. Methods. Contemporary data on the epidemiologic characteristics of FM and CWP are reviewed, and evidence for a neurobiological basis for these disorders is presented. In addition, possible predisposing, triggering, and maintaining factors for the development of these disorders are discussed. Results. Approximately 10% of the population have CWP, and approximately 4% have FM. The tender point criteria for FM have resulted in the common misconception among health care professionals that this spectrum of disorders is limited to women with high degrees of psychological distress. A hallmark of FM is the presence of non-nociceptive, central pain. There is evidence of centrally augmented pain processing, which can be detected both with sensory testing and by more objective measures (e.g., evoked potentials, functional neuroimaging). Discussion. An appreciation of the neurobiological basis for these disorders, and an understanding of some of the abnormalities of pain processing present in patients with FM, will hopefully provide greater understanding of these patients. It may also serve to decrease the level of frustration and improve the care experience of both chronic pain patients and physicians. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are associated with substantial physical disability. Determinants of self-reported physical disability are poorly understood. This investigation uses objective ambulatory activity monitoring to compare patients with FM and/or CFS with controls, and examines associations of ambulatory activity levels with both physical function and symptoms during activities of daily life. METHODS: Patients with FM and/or CFS (n = 38, mean +/- SD age 41.5 +/- 8.2 years, 74% women) completed a 5-day program of ambulatory monitoring of physical activity and symptoms (pain, fatigue, and distress) and results were compared with those in age-matched controls (n = 27, mean +/- SD age 38.0 +/- 8.6 years, 44% women). Activity levels were assessed continuously, ambulatory symptoms were determined using electronically time-stamped recordings at 5 time points during each day, and physical function was measured with the 36-item Short Form health survey at the end of the 5-day monitoring period. RESULTS: Patients had significantly lower peak activity levels than controls (mean +/- SEM 8,654 +/- 527 versus 12,913 +/- 1,462 units; P = 0.003) and spent less time in high-level activities when compared with controls (P = 0.001). In contrast, patients had similar average activity levels as those of controls (mean +/- SEM 1,525 +/- 63 versus 1,602 +/- 89; P = 0.47). Among patients, low activity levels were associated with worse self-reported physical function over the preceding month. Activity levels were inversely related to concurrent ambulatory pain (P = 0.031) and fatigue (P < 0.001). Pain and fatigue were associated with reduced subsequent ambulatory activity levels, whereas activity levels were not predictive of subsequent symptoms. CONCLUSION: Patients with FM and/or CFS engaged in less high-intensity physical activities than that recorded for sedentary control subjects. This reduced peak activity was correlated with measures of poor physical function. The observed associations may be relevant to the design of behavioral activation programs, because activity levels appear to be contingent on, rather than predictive of, symptoms. [ABSTRACT FROM AUTHOR]

Context: Gulf War veterans' illnesses (GWVI), multisymptom illnesses characterized by persistent pain, fatigue, and cognitive symptoms, have been reported by many Gulf War veterans. There are currently no effective therapies available to treat GWVI.Objective: To compare the effectiveness of cognitive behavioral therapy (CBT), exercise, and the combination of both for improving physical functioning and reducing the symptoms of GWVI.Design, Setting, and Patients: Randomized controlled 2 x 2 factorial trial conducted from April 1999 to September 2001 among 1092 Gulf War veterans who reported at least 2 of 3 symptom types (fatigue, pain, and cognitive) for more than 6 months and at the time of screening. Treatment assignment was unmasked except for a masked assessor of study outcomes at each clinical site (18 Department of Veterans Affairs [VA] and 2 Department of Defense [DOD] medical centers).Interventions: Veterans were randomly assigned to receive usual care (n = 271), consisting of any and all care received from inside or outside the VA or DOD health care systems; CBT plus usual care (n = 286); exercise plus usual care (n = 269); or CBT plus exercise plus usual care (n = 266). Exercise sessions were 60 minutes and CBT sessions were 60 to 90 minutes; both met weekly for 12 weeks.Main Outcome Measures: The primary end point was a 7-point or greater increase (improvement) on the Physical Component Summary scale of the Veterans Short Form 36-Item Health Survey at 12 months. Secondary outcomes were standardized measures of pain, fatigue, cognitive symptoms, distress, and mental health functioning. Participants were evaluated at baseline and at 3, 6, and 12 months.Results: The percentage of veterans with improvement in physical function at 1 year was 11.5% for usual care, 11.7% for exercise alone, 18.4% for CBT plus exercise, and 18.5% for CBT alone. The adjusted odds ratios (OR) for improvement in exercise, CBT, and exercise plus CBT vs usual care were 1.07 (95% confidence interval [CI], 0.63-1.82), 1.72 (95% CI, 0.91-3.23), and 1.84 (95% CI, 0.95-3.55), respectively. The OR for the overall (marginal) effect of receiving CBT (n = 552) vs no CBT (n = 535) was 1.71 (95% CI, 1.15-2.53) and for exercise (n = 531) vs no exercise (n = 556) was 1.07 (95% CI, 0.76-1.50). For secondary outcomes, exercise alone or in combination with CBT significantly improved fatigue, distress, cognitive symptoms, and mental health functioning, while CBT alone significantly improved cognitive symptoms and mental health functioning. Neither treatment had a significant impact on pain.Conclusion: Our results suggest that CBT and/or exercise can provide modest relief for some of the symptoms of chronic multisymptom illnesses such as GWVI. [ABSTRACT FROM AUTHOR]

Background: Mechanisms responsible for sensitivity to irritants such as tobacco smoke are poorly understood. A Tobacco Score questionnaire was developed to identify and characterize subjects with this sensitivity. For this pilot study, scores were assessed in populations of self-selected controls and a group with irritant sensitivity (Chronic Fatigue Syndrome, CFS).Method: Subjects graded the severity of 21 symptoms associated with tobacco exposure. Results were compared with other instruments and a measure of pain sensitivity (dolorimetry) in 116 control and 103 CFS subjects.Results: The Tobacco Score was positive in 16% of control and 51% of CFS subjects. Significant correlations were found between Tobacco Score, Irritant Rhinitis Score, and history of sinusitis. Intermediate relationships were found with history of allergic rhinitis, Systemic Com plaints Score, and Multiple Chemical Sensitivity. Factors having no influence included gender, the severity of CFS symptoms, pain thresholds, and allergy skin tests.Conclusions: Tobacco sensitivity was correlated with measures of upper airway irritation and nonallergic sensitivity to triggers such as weather changes. The spectrum of symptoms, high prevalence in CFS, and absence of a relationship to atopy suggest that these nonallergic irritant syndromes may share a common neuropathophysiology. [ABSTRACT FROM AUTHOR]

Background: Irritation symptoms after exposure to 'nonspecific' stimuli are often attributed to nonallergic rhinitis (vasomotor rhinitis). This is a heterogeneous syndrome of exclusion based on nasal symptoms with negative allergy skin tests.Method: Control (n = 114) and Chronic Fatigue Syndrome (CFS, n = 120) subjects scored the severity of nasal congestion and rhinorrhea sensations that they attributed to 9 irritants. The sum was the 'Irritant Rhinitis Score' (IRS, maximum 72). A positive IRS of >/= 19 defined 'Irritant Rhinitis.' Demographic, allergy skin test and other assessments were done to characterize the Irritant Rhinitis population.Results: Irritant Rhinitis was present in 11% of control and 47% of CFS subjects. In multivariate analysis, positive IRS was correlated with a history of rhinitis complaints, systemic complaints such as fatigue, sensations of congestion and rhinorrhea induced by meteorological conditions, tobacco smoke, odors, perfumes, and other volatile materials, and diagnoses of CFS and Multiple Chemical Sensitivity (MCS). Although atopy was not correlated to Irritant Rhinitis, 51% of allergic rhinitis subjccts had a positive IRS.Conclusions: The Irritant Rhinitis Score defined a population with irritant-induced nasal congestion and rhinorrhea who also had significant systemic complaints. Similar neural mechanisms may underlie the spectrum of Irritant Rhinitis, CFS and MCS. [ABSTRACT FROM AUTHOR]

Clinical studies have continued to suggest a relationship between silicone breast implants and chronic fatigue syndrome. Extensive epidemiologic studies, however, indicate that such a relationship is likely to be by chance and the successful lawsuits against producers of silicone breast implants are based on factors other than scientific proof. We present several perspectives on this issue which are probably relevant to other reports of putative etiologic agents for chronic fatigue syndrome. [ABSTRACT FROM AUTHOR]

Background: Chronic primary pain describes conditions where pain is the principal problem rather than a consequence of another disease. Primary pain is thought to be primarily owing to nociplastic pain (i.e. pain as a result of altered nociception despite the absence of tissue damage). Primary pain is often accompanied by other bothersome central nervous system (CNS)-driven symptoms, including disturbed sleep, mood, and cognition; however, it is unclear whether these symptoms precede onset of primary pain., Methods: In a prospective cohort study of the UK Biobank, we examined adults with no self-reported recent or chronic pain at baseline. Using linked primary care record data, we investigated the association between the number of CNS-driven symptoms and subsequent incidence of primary pain conditions. Multivariable regression analyses adjusted for sociodemographic and lifestyle factors., Results: Of 502 369 participants, 70 630 (14.0%) met the inclusion criteria, with a mean (range) age of 56.7 (40-70) yr, 51% being female. After 7.4 (range 0.5-11.02) yr, 12.2% developed a primary pain condition. We observed a positive relationship between the number of CNS-driven symptoms at baseline and risk of future primary pain (HR 1.43, 95% CI 1.34-1.52, P<0.001). Participants with more CNS-driven symptoms at baseline were also more likely to have chronic and more severe nociplastic pain, but not non-nociplastic pain at follow-up., Conclusions: In adults with no current self-reported pain, those with a greater number of CNS-driven symptoms at baseline were more likely to develop a primary pain condition. This suggests a potential opportunity for early intervention in mitigating the burden of primary pain., Competing Interests: Declaration of interests EK was supported by a National Institute for Health Research (NIHR) Pfizer Doctoral Fellowship for this research project (NIHR301808). DC and CK are supported by a National Institutes of Health (NIH) grant. AI received funding from UCB, unrelated to the current project, during the time of the project. The other authors declare that they have no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Chronic pain is common among Veterans, some of whom use cannabis for pain. We conducted a feasibility pilot study of a novel coaching intervention to help Veterans optimize use of medical cannabis products for pain management (NCT06320470)., Methods: The intervention drew from scientific literature, consultation with cannabis experts, Veteran input via a Community Advisory Board, and tenets of motivational interviewing. Participants were Veterans with chronic pain who endorsed current use or interest in using cannabis for pain management. Participants received up to 4 individual coaching sessions via videoconference, spaced approximately 2 weeks apart. We assessed feasibility (adherence, satisfaction, acceptability) and preliminary effects on pain symptoms 14 weeks after baseline. The primary outcome was the Patient Global Impression of Change (PGIC), and exploratory outcomes included domains from the Patient-Reported Outcomes Measurement Information System (PROMIS)-29., Results: Of 22 enrolled participants, 17 attended 4 coaching sessions, 2 attended 3 sessions, and 2 attended 2 sessions. Among those who completed end of intervention surveys (16/21), 87.5% were very or completely satisfied with the intervention and 81.3% rated coaching as very or extremely helpful. All participants reported improvement on the PGIC, with 63% reporting much or very much improvement. Participants reported statistically significant decreased pain intensity (7.1/10 vs. 5.7/10) and pain interference (T-score 66.3 vs. 61.8), and increased social satisfaction (T-score 41.4 vs. 44.3). Participants noted helpful intervention factors, including co-developing a personalized plan, discussing questions/concerns, and trying different approaches to cannabis-based treatment., Conclusions: In this feasibility pilot study of coaching on cannabis use for chronic pain among Veterans, participants were satisfied with the intervention and reported clinically significant improvements in pain symptoms. Our results support evaluating this intervention in a larger, efficacy trial., Competing Interests: Declarations. Ethics approval and consent to participate: The University of Michigan Institutional Review Board (IRB) approved all study methods and procedures under HUM00231159. Participants received up to $200 for participating in the study, with payment disbursed after each completed survey. This trial was registered to clinicaltrials.gov as NCT06320470. Consent for publication: All authors approve of this manuscript for publication. Competing interests: Dr. Boehnke has received grant funding from Tryp Therapeutics and Journey Biosciences for a clinical trial of psilocybin-assisted therapy and sits on a data safety and monitoring board for an ongoing clinical trial with Vireo Health (unpaid). He has received speaking fees for lectures from the Medical Cannabis Research Advocacy Alliance, Provide Holy Cross Medical Center, the Southern Pain Society, and the Michigan Center of Clinical Systems Improvement, and an honorarium for developing a podcast on fibromyalgia with Viatris Inc. Dr. Clauw has received consulting fees from AbbVie, Heron Therapeutics, Aptinyx, Neumentum, Regoneron Pharmaceuticals, Swing Therapeutics, Virios Therapeutics, Allergan Sales, Eli Lilly and Company, H. Lundbeck A/S, Pfizer, Samumed, and Tonix Pharmaceuticals. Dr. Williams has been a consultant for Swing Therapeutics and Community Health Focus. Dr. Litinas has done consulting work with University of Michigan as a subject matter expert, coached and trained consumers and dispensary employees on comprehensive cannabis education, and has a cannabinoid-based product brand. Dr. Bergmans has consulted for Tonix Pharmaceuticals. All other authors declare no conflicts of interest., (© 2025. The Author(s).)

Chronic ocular surface pain (COSP) refers to interrelated symptoms such as burning, aching, and irritation and can occur as an isolated condition or comorbid with numerous ocular disorders, including dry eye syndrome Treatments for COSP are largely aimed at the ocular surface and modulating pain arising from damaged corneal nerves; however, the average impact of these treatments on COSP are low to absent. A potential explanation for this is that, in a subset of patients with COSP, individuals have amplified and/or dysregulated neural signaling and sensory processing within the central nervous system (CNS). As in other chronic pain conditions, this might be the pathogenic mechanism primarily responsible for maintaining pain - a phenomenon now referred to as nociplastic pain. The key clinical features of nociplastic pain include symptoms out of proportion to signs, regional or widespread pain, the presence of other chronic pain conditions, and non-pain CNS mediated symptoms (e.g., sleep disorders). We provide an overview for eye care clinicians of nociplastic pain and delineate the emerging evidence for the presence of nociplastic pain among some individuals with COSP. We highlight gaps in our current understanding of nociplastic pain in COSP and provide clinicians with specific tools that may aid in the assessment and management of nociplastic pain., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lindsey B. De Lott reports financial support was provided by Research to Prevent Blindness. Lindsey B. De Lott reports financial support was provided by National Institutes of Health. Anat Galor reports financial support was provided by National Institutes of Health. Anat Galor reports financial support was provided by Research to Prevent Blindness. Anat Galor reports financial support was provided by US Department of Veterans Affairs. Daniel Clauw reports financial support was provided by National Institutes of Health. Steven Harte reports financial support was provided by National Institutes of Health. Chelsea Kaplan reports financial support was provided by National Institutes of Health. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Background: Central sensitization is an important mechanism underlying many chronic pain conditions. Chronic pain and alcohol use disorder (AUD) are highly comorbid. Despite great scientific interest in brain mechanisms linking chronic pain and AUD, progress has been impeded by difficulty assessing central sensitization in AUD., Objective: The present study is the first to employ a validated surrogate measure to describe central sensitization in a clinical sample with AUD., Methods: Participants with AUD ( n  = 99) were recruited from an academic addiction treatment center. A well-established surrogate measure of central sensitization, The American College of Rheumatology Fibromyalgia Survey Criteria (ACRFMS) was administered. Participants also responded to questions about quality of life (RAND-36), and AUD. Descriptive analyses and Spearman's rho correlations were performed., Results: Chronic pain and evidence of central sensitization were prevalent. Greater central sensitization was associated with worse health-related quality of life. Participants higher in central sensitization expressed greater endorsement of pain as a reason for AUD onset, maintenance, escalation, treatment delay, and relapse., Conclusion: The present study bolsters prior assertions that AUD and chronic pain might compound one another via progressive sensitization of shared brain circuitry. These results may inform future mechanistic research and precision AUD treatment.

Background/objectives: Chronic pain is an opioid use disorder (OUD) treatment barrier and associated with poor outcomes in OUD treatment including relapse. Fibromyalgia is a chronic pain condition related to central nervous system substrates that overlap with the brain disease model of OUD. We know of no studies that have looked at non-treatment seeking individuals, to see if fibromyalgia might represent a barrier to OUD treatment. Given many non-treatment-seeking individuals previously attempted recovery before experiencing relapse, and chronic pain is a known precipitant of relapse, fibromyalgia might be a currently unappreciated modifiable factor in OUD relapse and, potentially, a barrier to treatment reengagement among those not currently seeking treatment. This study aimed to determine if fibromyalgia is associated with greater odds of agreeing that 'I have tried to stop using opioids before, but pain caused me to relapse' among non-treatment seeking individuals with OUD., Methods: This cross-sectional study recruited non-treatment-seeking individuals with OUD ( n  = 141) from a syringe service program. Ordinal logistic regression was used to determine if the presence of fibromyalgia increased the odds of agreement with prior pain-precipitated relapse., Results: Fibromyalgia was identified in 35% of study participants and associated with 125% greater odds of strongly agreeing that pain had previously caused them to relapse, even after accounting for relevant covariates, including age, sex, depression, anxiety, OUD severity, and pain severity., Conclusions: This study provides early evidence that the presence of fibromyalgia may be associated with increased odds of pain-precipitated OUD relapse.

Background: The NIH Pain Common Data Elements (CDEs) provide a standardized framework for pain research, but their implementation and interpretation present challenges., Objectives: To review the NIH CDE Program's selected pain domains, provide best practices for implementing required questions, and offer a checklist for appropriate CDE use in clinical trials and secondary data analysis., Methods: This work analyzed the ten core pain research domains selected by the NIH CDE Program and discuss their limitations and considerations for use., Results: The manuscript provides an overview of the ten core pain research domains, including pain intensity, interference, physical function, sleep, catastrophizing, depression, anxiety, global impression of change, substance use screening, and quality of life. It offers sample scenarios for implementing required questions and presents a checklist to guide researchers in using pain CDEs effectively for clinical trials and secondary data analysis., Discussion: Key challenges identified include contextual variability, lack of validation across all pain conditions and populations, and potential misuse or misinterpretation of measures. This work proposes solutions such as supplementary measures, context-specific guidance, comprehensive training programs, and ongoing refinement of the CDE framework., Conclusion: While NIH Pain CDEs are valuable tools for standardizing pain assessment in research, addressing challenges in their implementation and interpretation is crucial for improving the consistency, validity, and interpretability of pain research data, ultimately advancing the field and enhancing patient care., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Academy of Pain Medicine.)

Abstract: Chronic ocular pain (COP) is a leading cause of eye care visits in the US and has a substantial impact on quality of life and visual functioning. Although many conditions underlie COP, such as dry eye disease or post-herpetic neuralgia, some people experience pain without significant ocular signs on examination or known risk factors (eg, traumatic injury). Antidepressant medications that act primarily on the central nervous system, such as tricyclic antidepressants and serotonin and norepinephrine reuptake inhibitors, are often used to treat patients with COP, but a recent Cochrane review and network meta-analysis investigating 25 different antidepressants concluded that only two serotonin and norepinephrine reuptake inhibitors, have sufficient data to support their use in chronic pain. For all other medications, the evidence was of low certainty. We contend that while these medications are not a cure-all for chronic pain or COP, it is premature to conclude that these medications have no role in their treatment. We provide a rationale for continued use of antidepressant medications as part of a multimodal targeted treatment for patients with COP., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: In the ICU, opioids treat pain and improve ventilator tolerance as part of an analgosedation approach. Identifying predictors of opioid consumption during the ICU course might highlight actionable items to reduce opioid consumption., Objectives: To identify risk factors for opioid use during a postoperative ICU course., Design, Setting, and Participants: Patients enrolled in the Michigan Genomics Initiative single-center prospective observational cohort study completed baseline preoperative sociodemographic and mental/physical health questionnaires and provided blood samples for genetic analysis. Included patients were 18 years old and older, admitted to ICU postoperatively, and received opioids postoperatively., Main Outcomes and Measures: The primary outcome was ICU mean daily oral morphine equivalent (OME) use. The association between OME and phenotypic risk factors and genetic variants previously associated with pain were analyzed through univariable and multivariable linear regression models., Results: The cohort consisted of 1865 mixed-surgical patients with mean age of 56 years (sd, 15 yr). Preoperative opioid users were more likely to continue to receive opioids throughout their ICU stay than opioid-naive patients. OME (log10 scale) was most strongly associated with ICU mechanical ventilation (β = 0.27; 95% CI, 0.15-0.38; p < 0.0001; effect size 1.85 for receiving > 24 hours of mechanical ventilation), preoperative opioid use (β = 0.22; 95% CI, 0.16-0.29; p < 0.0001; effect size 1.67 for receiving preoperative opioids), major surgery (β = 0.21; 95% CI, 0.12-0.30; p < 0.0001; effect size 1.62 compared with minor surgery), and current/former illicit drug use (β = 0.12; 95% CI, 0.01-0.23; p = 0.04; effect size 1.30 for drug use). Younger age, centralized pain, and longer anesthetic duration were also significantly associated with OME but with smaller effect sizes. Selected genetic variants (FKBP5, COMT, and OPRM1) were not associated with OME use., Conclusions and Relevance: Mechanical ventilation and preoperative opioids were the strongest risk factors for postoperative ICU opioid consumption, whereas psychologic factors and genetic variants were not associated., Competing Interests: Dr. Brummett is a consultant for Vertex Pharmaceuticals and Merck Pharmaceuticals; he provides expert medical testimony; and he previously served as a consultant for Heron Therapeutics. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: Black people have disproportionately high morbidity and mortality due to systemic lupus erythematosus (SLE). Features of social and occupational environments can protect against poor health outcomes., Objective: We aimed to characterize how SLE intersects with interpersonal relationships and employment among Black adults to inform tailored care approaches and public policies that could alleviate racial inequities in SLE., Methods: We used a qualitative, interpretive description approach that involved semi-structured interviews with Black adults who had SLE. The interview guide included questions about SLE diagnosis, impacts on day-to-day life, and symptom management. We analyzed the de-identified transcripts using inductive, thematic analysis with input from representatives of the study population. Our theme development focused on how SLE (i.e., symptoms, severity, management) intersected with interpersonal relationships and employment., Results: This study included 30 interviews (97 % female, age range = 18-65 years). Among participants, 30 % were not working due to unemployment or disability and 23 % reported a lack of emotional support. Our analysis resulted in three main themes: 1) The bi-directional relationship between employment and SLE; 2) The positive and negative effects of connecting with other people who have SLE; and 3) The moderating role of relationships with family and friends, and the impact on self-identity., Conclusions: This study describes features of social and occupational environments that influence SLE management and wellbeing. Our results highlight directions for further study that could identify and address how systemic racism affects race-based inequities in SLE., Competing Interests: Declaration of competing interest Dr. Bergmans reported receiving consulting fees from Tonix Pharmaceuticals Inc and receiving grants from AstraZeneca, GlaxoSmithKline, and Aurinia Pharmaceuticals outside the submitted work. Dr. Kahlenberg reported receiving grants from Q32 Bio, Bristol-Myers Squibb, Ventus Therapeutics, ROME Therapeutics, and Janssen outside the submitted work and serving on advisory boards for AstraZeneca, Biogen, Danger Bio, Eli Lilly, Exo Therapeutics, GlaxoSmithKline, Gilead, Bristol-Myers Squibb, Lupus Therapeutics, Aurinia Pharmaceuticals, Ventus Therapeutics, Vividion Therapeutics, and ROME Therapeutics., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Rheumatologists and rheumatology have had a prominent role in the conceptualisation of nociplastic pain since the prototypical nociplastic pain condition is fibromyalgia. Fibromyalgia had been previously known as fibrositis, until it became clear that this condition could be differentiatied from autoimmune disorders because of a lack of systemic inflammation and tissue damage. Nociplastic pain is now thought to be a third descriptor/mechanism of pain, in addition to nociceptive pain (pain due to peripheral damage or inflammation) and neuropathic pain. Nociplastic pain can occur in isolation, or as a co-morbidity with other mechanisms of pain, as commonly occurs in individuals with autoimmune disorders. We now know that the cardinal symptoms of nociplastic pain are widespread pain (or pain in areas not without evidence of inflammation/damage), accompanied by fatigue, sleep and memory issues. There is objective evidence of amplification/augmentation of pain, as well as of non-painful stimuli such as the brightness of lights and unpleasantness of sound or odors. Nociplastic pain states can be triggered by a variety of stressors such as trauma, infections and chronic stressors. Together these features suggest that the central nervous system (CNS) is playing a major role in causing and maintaining nociplastic pain, but these CNS factors may in some be driven by ongoing peripheral nociceptive input. The most effective drug therapies for nociplastic pain are non-opioid centrally acting analgesics such as tricyclics, serotonin-norepinephrine reuptake inhibitors and gabapentinoids. However the mainstay of therapy of nociplastic pain is the use of a variety of non-pharmacological integrative therapies, especially those which improve activity/exercise, sleep and address psychological co-morbidities., Competing Interests: Competing interests: DJC has performed consulting for Tonix, Theravance, Virios and Swing Therapeutics and has been involved in litigation against opioid manufacturers and distributors as well as defended Merck in litigation against the Gardasil vaccine., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Introduction: Chronic pain is a personal experience influenced by multiple biopsychosocial factors. Using a pain intensity measure alone to assess the effectiveness of a chronic pain intervention fails to fully evaluate its impact on the multifaceted chronic pain experience. The holistic minimal clinically important difference (MCID) is a composite outcome developed to provide a comprehensive assessment of chronic pain in response to intervention, across 5 outcome domains: pain intensity, health-related quality of life, sleep quality, physical, and emotional function. To focus on domains where the individual need is greatest, the holistic MCID reflects the cumulative MCID averaged over only the domains where subjects were impaired preintervention., Objectives: To assess the internal and construct validity of the Holistic MCID score to inform its future use as an evidence-based tool., Methods: This validation study was undertaken using data from the EVOKE trial with 111 patients up to 24-month follow-up. Internal consistency of the holistic MCID was assessed using Cronbach alpha statistic and dimensional exploration using principal component analysis., Results: The holistic MCID measure demonstrated strong internal consistency with Cronbach alpha >0.7 at all follow-ups. Principal component analysis showed one overarching holistic dimension to be present in the composite. Construct validity was demonstrated by an increase in the holistic MCID score being associated with both increased Patients' Global Impression of Change, EuroQol visual analogue scale score, and each of the outcome domains in a "leave-one-out" analysis (all P < 0.001)., Conclusion: The holistic MCID provides a valid measure for the comprehensive, personalized assessment of response after a chronic pain intervention. The validity of the holistic MCID requires further confirmation in other chronic pain populations and with different interventions., Competing Interests: R.S.T. reports consultancy fees from Medtronic, Nevro and Saluda Medical outside the submitted work. C.M.M. is employed by NAMSA, a company that provides consulting and testing services to medical device manufacturers. N.A.M. reports receiving grants from Neuros, Mesoblast, and Vivex Biologics, as well as consulting as a medical monitor for Saluda Medical, Nevro, Vivex Biologics, Mainstay, Sollis Therapeutics, and Vertos outside the submitted work. J.W.K. is an advisory board member for Boston Scientific, Medtronic, Abbott, and Saluda Medical. J.E.P. reports research and consulting fees from Saluda Medical during the conduct of the study; consultancy for Abbott, Medtronic, Saluda Medical, Flowonix, SpineThera, Vertos, Vertiflex, SPR Therapeutics, Tersera, Aurora, Spark, Ethos, Biotronik, Mainstay, WISE, Boston Scientific, and Thermaquil outside the submitted work; has received grant and research support from: Abbott, Flowonix, Aurora, Painteq, Ethos, Muse, Boston Scientific, SPR Therapeutics, Mainstay, Vertos, AIS, and Thermaquil outside the submitted work; and is a shareholder of Vertos, SPR Therapeutics, Painteq, Aurora, Spark, Celeri Health, Neural Integrative Solutions, Pacific Research Institute, Thermaquil, and Anesthetic Gas Reclamation. C.W.H. has received consultancy fees from Saluda Medical and Genecentrix outside the submitted work. S.J.C. reports receiving grants from Saluda Medical, Vertos, Mainstay, and Vivex outside the submitted work. L.K. reports receiving grants from Nevro, Neuros, Avanos, Medtronic, Neuralace, and Xalud Therapeutics and financial support from Nevro, Avanos, and Saluda Medical outside the submitted work. C.A.G. reports personal fees and other from SPR, and personal fees from Nevro, Nalu, Biotronik, Boston Scientific and Saluda Medical outside the submitted work. E.A.P. has received research support from Mainstay, Medtronic, Neuros Medical, Nevro Corp, ReNeuron, SPR, and Saluda Medical outside the submitted work, as well as personal fees from Abbott Neuromodulation, Biotronik, Medtronic Neuromodulation, Nalu, Neuros Medical, Nevro, Presidio Medical, Saluda Medical, and Vertos outside the submitted work. She holds stock options from SynerFuse and neuro42. K.V.P. is a consultant and speaker for Abbott. S.E. reports consultancy fees from Medtronic, and Mainstay Medical outside the submitted work. He has received department research funding from the National Institute of Health Research, Saluda Medical and Medtronic. R.M.L. is an uncompensated consultant for Biotronik, Abbott, Nalu, Saluda Medical, and Mainstay Medical and has stock options from Nalu and Saluda Medical. C.G. reports payment to his institution (for part of his salary) and stock options received from Mainstay, personal fees from Mainstay, Saluda Medical, Persica, and Iliad outside the submitted work, research funded by Sollis, expert witness testimony fees, and serves as Editor-in-Chief of Pain Practice. S.D. has received consulting payments from Averitas Pharma and Biotronik outside the submitted work. A.A. reports consultancy for Medtronic, Avanos, and StimWave outside the submitted work. P.B. reports consulting fees from Abbott and PainTEQ outside the submitted work. E.H., A.L., N.S. and R.V.D. are employees of Saluda Medical. R.V.D. has previously received consultancy fees from Mainstay Medical, Medtronic, and Saluda Medical. D.J.C. has consulted for AbbVie, Heron Therapeutics, Aptinyx, Neumentum, Regeneron Pharmaceuticals, Swing Therapeutics, Virios Therapeutics, Allergan Sales, Eli Lilly and Company, H. Lundback A/S, Pfizer, Samumed, Tonix Pharmaceuticals. T.J.N. has received consultancy fees from Saluda Medical outside the submitted work. The remaining authors declare no conflict of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.)

Abstract: Ecological momentary assessment (EMA) allows for the collection of participant-reported outcomes (PROs), including pain, in the normal environment at high resolution and with reduced recall bias. Ecological momentary assessment is an important component in studies of pain, providing detailed information about the frequency, intensity, and degree of interference of individuals' pain. However, there is no universally agreed on standard for summarizing pain measures from repeated PRO assessment using EMA into a single, clinically meaningful measure of pain. Here, we quantify the accuracy of summaries (eg, mean and median) of pain outcomes obtained from EMA and the effect of thresholding these summaries to obtain binary clinical end points of chronic pain status (yes/no). Data applications and simulations indicate that binarizing empirical estimators (eg, sample mean, random intercept linear mixed model) can perform well. However, linear mixed-effect modeling estimators that account for the nonlinear relationship between average and variability of pain scores perform better for quantifying the true average pain and reduce estimation error by up to 50%, with larger improvements for individuals with more variable pain scores. We also show that binarizing pain scores (eg, <3 and ≥3) can lead to a substantial loss of statistical power (40%-50%). Thus, when examining pain outcomes using EMA, the use of linear mixed models using the entire scale (0-10) is superior to splitting the outcomes into 2 groups (<3 and ≥3) providing greater statistical power and sensitivity., (Copyright © 2024 International Association for the Study of Pain.)

Introduction: Medical cannabis users tend not to trust or rely on health care providers regarding cannabis advice. Previous surveys of physicians have focused on favorability toward medical cannabis. The current study assesses how physicians interact with patients regarding cannabis in their day-to-day practice, and whether and how they address important topics such as use patterns and substituting cannabis for medications. We predicted that physicians would generally perceive cannabis dispensary staff and caretakers as not competent in addressing patient health needs and would not be likely to use their recommendations. Methods: Physicians in a university-affiliated health system completed an anonymous online survey. The survey assessed physicians' cannabis related education experiences, perceptions of their knowledge of and competence regarding medical cannabis, and the content of cannabis related discussions with patients. We also examined perceptions of the sources of influence on patients regarding cannabis and physicians' attitudes toward medical cannabis dispensary staff and medical cannabis caregivers (MCCs). Results: A few physicians (10%) had ever signed a medical cannabis authorization form for their patients, consistent with their perceptions of low knowledge and competence in this area. Discussions on cannabis primarily focus on risks (63%) rather than dosage (6%) and harm reduction (25%). Physicians see their influence on patients as weak compared with other information sources and have generally unfavorable attitudes toward medical cannabis dispensary staff and MCCs. Conclusion: Greater integration of medical cannabis knowledge is needed at all levels of medical and clinical education to address the potential harm to patients if they receive no guidance. Continued research is needed to provide a strong scientific basis for developing treatment guidelines and standardized medical education for medical cannabis use.

Background: International guidelines have recommended cognitive behavioural therapy, including acceptance and commitment therapy (ACT), as it offers validated benefits for managing fibromyalgia; however, it is inaccessible to most patients. We aimed to evaluate the effect of a 12-week, self-guided, smartphone-delivered digital ACT programme on fibromyalgia management., Methods: In the PROSPER-FM randomised clinical trial conducted at 25 US community sites, adult participants aged 22-75 years with fibromyalgia were recruited and randomly assigned (1:1) to the digital ACT group or an active control group that offered daily symptom tracking and monitoring and access to health-related and fibromyalgia-related educational materials. Randomisation was done with a web-based system in permuted blocks of four at the site level. We used a blind-to-hypothesis approach in which participants were informed they would be randomly assigned to one of two potentially effective therapies under evaluation. Research staff were not masked to group allocation, with the exception of a masked statistics group while preparing statistical programming for the interim analysis. The primary endpoint was patient global impression of change (PGIC) response rate at week 12. Analyses were by intention to treat. The trial was registered with ClinicalTrials.gov, NCT05243511 (now fully closed)., Findings: Between Feb 8, 2022, and Feb 2, 2023, 590 individuals were screened, of whom 275 (257 women and 18 men) were randomly assigned to the digital ACT group (n=140) and the active control group (n=135). At 12 weeks, 99 (71%) of 140 ACT participants reported improvement on PGIC versus 30 (22%) of 135 active control participants, corresponding to a difference in proportions of 48·4% (95% CI 37·9-58·9; p<0·0001). No device-related safety events were reported., Interpretation: Digital ACT was safe and efficacious compared with digital symptom tracking in managing fibromyalgia in adult patients., Funding: Swing Therapeutics., Competing Interests: Declaration of interests RMG reports being a consultant and receiving stock options or bond holdings from Swing Therapeutics. LMM reports being a consultant to Swing Therapeutics. DAW reports being a consultant to Community Health Focus and Swing Therapeutics and receiving grants from the National Institutes of Health and Patient-Centered Outcome Research Institute. YD, NV, ZG, KG, and ACK report receiving stock options and salary from Swing Therapeutics. MJR reports being a founder, chief executive officer, and receiving stock options and salary from Swing Therapeutics. JMZ and DR report receiving grants from Swing Therapeutics (as study site investigators for the clinical investigation presented in this manuscript). DR reports salary from Bristol Myers Squibb. ALC reports being a consultant to Scilex Pharmaceuticals and Swing Therapeutics, and receiving grants from the National Institutes of Health, the US Department of Defense, and the Cystic Fibrosis Foundation. DJC reports being a consultant to AbbVie, Allergan, Aptinyx, Eli Lilly, H Lundbeck A/S, Heron Therapeutics, Neumentum, Regeneron Pharmaceuticals, Samumed, Swing Therapeutics, Tonix Pharmaceuticals, Virios Therapeutics, and serving as speaker for or receiving honoraria from Fasken Martineau DuMoulin LLP, Kellogg, Hansen, Todd, Figel & Frederick, Marks & Clerk Law, Nix Patterson, Pfizer, Zuber Lawler, and Del Duca. BV reports being an employee of Rho and a consultant to Swing Therapeutics. LMA reports being a consultant to Analgesic Solutions, Aptinyx, Axsome Therapeutics, Eliem Therapeutics, Ono Pharmaceuticals, and Scilex, and receiving grants from AbbVie, Aptinyx, Otsuka, Swing Therapeutics (principal investigator for the clinical investigation presented in this manuscript), Teva Pharmaceuticals, Tonix Pharmaceuticals, and Virios Therapeutics. JVL reports receiving a grant from Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública., (Copyright © Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Importance: National estimates regarding the frequency of presentations and patterns of care for eye pain are unknown. This information could guide research and clinical efforts to optimize outcomes., Objective: To estimate eye pain visits in the US in the outpatient and emergency department (ED) settings., Design, Setting, and Participants: This retrospective cross-sectional study of National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey data (2008-2019) analyzed a population-based sample of visits to outpatient clinics and EDs. The sample consisted of patients presenting with eye pain. Data were analyzed from September 2023 to April 2024., Main Outcomes and Measures: Weighted sample data estimated outpatient and ED eye pain presentations including patient and clinician characteristics, diagnoses (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10]), and disposition., Results: From 2008 through 2019, 4.6 million (95% CI, 3.9 million to 5.3 million) outpatient and 1.0 million (95% CI, 0.8 million to 1.1 million) ED eye pain visits occurred annually. Patients were predominantly women (63.2% [95% CI, 59.4%-67.0%]) and older than 60 years (46.6% [95% CI, 42.4%-51.0%]) in the outpatient setting. Patients presenting to the ED were more often men (51.8% [95% CI, 48.7%-55.0%]) and aged younger than 45 years (aged <15 years: 16.4% [95% CI, 13.9%-18.8%]; 15-24 years: 19.2% [95% CI, 16.6%-21.7%]; and 25-44 years: 35.6% [95% CI, 32.7%-38.5%]). In nearly half of outpatient eye pain visits, the major problem was classified as nonacute (2.0 million [95% CI, 1.6 million to 2.3 million]). Eye pain was the primary reason for the visit (RFV) in 42.0% (95% CI, 37.8%-46.2%) of outpatient visits and 66.9% (95% CI, 62.9%-70.9%) of ED eye pain visits. It was the only RFV in 18.3% (95% CI, 15.0%-21.7%) of outpatient and 32.7% (95% CI, 29.0%-36.4%) of ED eye pain encounters. Ophthalmologists evaluated the largest number of outpatient visits (45.3% [95% CI, 38.8%-51.7%). The primary diagnosis was non-vision threatening for most outpatient (78.5% [95% CI, 56.8%-100%]) and ED (69.9% [95% CI, 62.1%-77.7%]) visits when eye pain was the primary RFV. Additional follow-up was scheduled in 89.4% (95% CI, 86.2%-92.6%) of visits., Conclusions and Relevance: More than 5 million eye pain visits occur annually; the largest percentage are outpatient with ophthalmologists. Most diagnoses were non-vision threatening in both the outpatient and ED setting and resulted in additional care. Expanding therapeutic approaches to treat the causes of eye pain may reduce the burden on the health care system and optimize outcomes.

Background: Chronic pain affects over 100 million Americans, with a disproportionately high number being Veterans. Chronic pain is often difficult to treat and responds variably to medications, with many providing minimal relief or having adverse side effects that preclude use. Cannabidiol (CBD) has emerged as a potential treatment for chronic pain, yet research in this area remains limited, with few studies examining CBD's analgesic potential. Because Veterans have a high need for improved pain care, we designed a clinical trial to investigate CBD's effectiveness in managing chronic pain symptoms among Veterans. We aim to determine whether CBD oral solution compared to placebo study medication is associated with greater improvement in the Patient Global Impression of Change (PGIC)., Methods: We designed a randomized, double-blind, placebo-controlled, pragmatic clinical trial with 468 participants. Participants will be randomly assigned in a 1:1 ratio to receive either placebo or a CBD oral solution over a 4-week period. The trial is remote via a smartphone app and by shipping study materials, including study medication, to participants. We will compare the difference in PGIC between the CBD and placebo group after four weeks and impacts on secondary outcomes (e.g., pain severity, pain interference, anxiety, suicide ideation, and sleep disturbance)., Discussion: Once complete, this trial will be among the largest to date investigating the efficacy of CBD for chronic pain. Findings from this clinical trial will contribute to a greater knowledge of CBD's analgesic potential and guide further research. Given the relative availability of CBD, our findings will help elucidate the potential of an accessible option for helping to manage chronic pain among Veterans., Trial Registration: This protocol is registered at clinicaltrials.gov under study number NCT06213233., (© 2024. The Author(s).)