Sensory organization at the spinal segment level is commonly inferred from dermatomal maps that assume a fixed correspondence between cutaneous regions and spinal segments. However, based on the complexities of spinal neuroanatomy and neurophysiology, the distribution of sensory signals within the cord may be broader and less segment-specific than dermatomal maps suggest, leaving the segment-level localization of sensory-evoked activity in humans uncertain. Spinal cord functional magnetic resonance imaging (fMRI) is currently the only technique capable of noninvasively mapping sensory activity with high spatial resolution in the human spinal cord. However, its application remains technically challenging and is limited by the uncertainty in segmental localization. In this study, we leveraged recent advancements in spinal cord fMRI, including spinal nerve rootlet-based spatial normalization, to investigate how sensory information is represented and distributed within the human spinal cord during electrocutaneous stimulation of the third digit of the right hand (i.e., C7 dermatome). Forty healthy adults were scanned with electrocutaneous stimulation at four individualized intensities across multiple runs to quantify (i) the rostrocaudal distribution of sensory-evoked activity, (ii) intensity-dependent changes in detectability and localization, and (iii) the effect of normalization strategy on segmental localization. Across participants, stimulation produced activation localized in the lower cervical cord (e.g., C6-C8), with the most consistent segmental localization near C7. Stronger stimulation increased detectability and produced more consistent segmental localization across participants. Importantly, normalization that incorporated nerve rootlet landmarks sharpened localization and improved sensitivity relative to conventional intervertebral disc-based alignment. This highlights the value of functionally relevant anatomical landmarks for group inference in the spinal cord. Responses were strongest in the initial run and attenuated with repetition, suggesting habituation or adaptation that can bias multi-run paradigms if unmodeled. Together, our results define practical acquisition and analysis conditions (e.g., stimulation strength, anatomical alignment strategy, and run structure) under which segment-level spinal sensory responses can be detected, thereby supporting more reliable studies of human spinal cord future basic and translational studies, including pain mechanisms, sensory function, and spinal injury.

OBJECTIVE:Chronic migraine (CM) is a condition marked by highly frequent, intense, and disabling headaches. However, less commonly examined symptoms, such as persistent fatigue, widespread non-cephalic pain, and post-traumatic stress disorder, may also play a key role in migraine-relevant clinical outcomes. METHODS:The current study utilized retrospective clinical registry data from 704 treatment-seeking patients with CM to examine longitudinal trajectories of pain intensity and pain-related life interference using linear growth modeling. RESULTS:High levels of co-occurring non-cephalic pain (71.9% of patients) were noted in this sample. Patients endorsing more widespread pain reported higher average levels of pain intensity over time (β = 0.189 [0.103-0.275], P < .001) and less improvement in pain interference over time (β = 0.328 [0.131-0.525], P = .001). Additional findings included greater reductions in pain interference among patients with higher baseline levels of pain intensity (β = -0.185 [-0.351 to -0.020], P = .028) and fatigue (β = -0.280 [-0.493 to -0.067], P = .010) and non-significant associations between post-traumatic stress symptoms and pain intensity and pain interference in all models. CONCLUSIONS:The current findings suggest that clinical factors sometimes overlooked in headache research, such as co-occurring non-cephalic pain and fatigue, may contribute to trajectories of treatment response and psychosocial function in CM. Future research may benefit from examining these factors in headache-specific treatment settings and in the context of examining the effects of multidisciplinary care on patients with complex symptom presentations.

Behavioral pain treatments are recommended as best practice for chronic pain management, yet remain understudied in people taking long-term opioids despite the critical need to develop effective non-pharmacological approaches for this vulnerable population. A randomized controlled trial tested whether a single-session, Zoom-delivered pain relief skills class (Empowered Relief; ER) lowers opioid use in adults with chronic pain receiving long-term opioid therapy. Two hundred thirteen participants (79 % women; median morphine equivalent daily dose 68 mg; 59% on disability; 26 % with prescription opioid misuse) were allocated 1:1 to one of two interventions: ER or an attention-matched health-education control- with both interventions taught by instructors involved in prior trials showing efficacy. Outcomes were assessed at baseline, 1, and 3 months. The primary endpoint, self-reported opioid dose at 3 months, showed no between-group difference (median change -2 mg vs -1 mg, P = 0.73) and no significant time effect. Pain interference likewise remained unchanged. Across groups, modest improvements appeared in pain intensity (mean -0.6/10, 95 % CI -0.9 to -0.3) and pain catastrophizing (-1.4/52, 95 % CI -2.4 to -0.4). The skills class produced greater gains in PROMIS Global Mental Health than control (group × time β = 1.2, P = 0.007), and participant satisfaction was higher (96 % vs 82 % rating ≥ 8/10). Attendance exceeded 85 %, and no adverse events occurred. ER is feasible and acceptable but insufficient to reduce opioid dose; integration with clinician-guided tapering protocols warrants study. ClinicalTrials.gov NCT03950791. PERSPECTIVE: Despite prior success in non-opioid and opioid samples, a two-hour telehealth pain relief skills class did not lessen opioid use in this complex opioid-treated cohort, though it modestly improved mental health. The findings suggest population-specific factors matter, and that brief behavioral training should be embedded within broader, taper-supportive care pathways, when opioid reduction is the goal.

Chronic pain affects nearly 70% of individuals following traumatic spinal cord injury (SCI) and is frequently reported as a disabling and undertreated complication. While disparities in SCI recovery are well-documented, evidence in chronic pain remains limited, with prior studies involving smaller cohorts and evaluating isolated social determinants rather than their intersectional contributions. We conducted a retrospective cohort study using the US Spinal Cord Injury Model Systems database, including 3514 adults with traumatic SCI. Exposures were race/ethnicity (non-Hispanic White, non-Hispanic Black), annual income (<$25,000 vs ≥$25,000), and education (high school or less vs higher). Outcomes were pain severity (0-10 numeric rating) and pain interference (SF-12; severe[3-4] vs minimal/moderate[0-2]). Models adjusted for demographic and injury characteristics. Intersectional analyses quantified the combined effects of multiple social disadvantages, and causal mediation analyses estimated average causal mediation effects (ACME). Non-Hispanic Black, lower-income, and lower-education participants had higher pain severity and more frequent severe pain interference than their counterparts (all p<0.0001). Non-Hispanic Black participants, low-income, low-education participants had +2.43 points (95%CI 2.06-2.79) higher pain severity and 2.96-fold (95%CI 2.15-4.07) higher odds of severe pain interference than non-Hispanic White, higher-income, higher-education participants (q<0.0001). Mobility scores, days out-of-the-house, private health insurance, and perceived health status significantly mediated disparities in pain severity (ACME 0.158-0.312) and pain interference (ACME 0.017-0.043; all q<0.001). Chronic pain after traumatic SCI disproportionately affects socially disadvantaged groups. These findings highlight intersectional disparities and identify modifiable mediators as targets for interventions to reduce inequitable pain outcomes following traumatic SCI. PERSPECTIVE: This retrospective multicenter cohort study quantified intersectional disparities in chronic pain one year following spinal cord injury and characterized modifiable individual and structural mediators that account for these inequities.

Background Systemic lupus erythematosus (SLE) presents substantial life challenges, reflecting the complex and heterogeneous nature of the disease. Pain is common and often one of the earliest manifestations. Skill-based behavioral pain treatments are often inaccessible to patients with SLE, and no SLE-specific evidence exists to guide patient and clinician treatment choices. To fill a pressing evidence gap for SLE pain treatment, the Lupus PROGRESS (Pain Relief With Online Groups That Empower Skill-Based Symptom Reduction) trial will compare a lower-burden evidence-based behavioral pain treatment with online multisession cognitive behavioral therapy (CBT; the gold standard behavioral treatment for chronic pain) while also enhancing diversity and representativeness among patient advisors and study participants. Objective Lupus PROGRESS is a national, pragmatic, randomized noninferiority trial comparing the effectiveness of 2 evidence-based behavioral pain treatments (online 8-session CBT vs 1 session the Empowered Relief program; Stanford University) in adults with SLE and chronic pain in the United States for reducing pain intensity and pain interference at 3 months after treatment (multiple primary end points). Methods In total, 150 adults with SLE and pain (≥3 months, intensity of ≥3/10) will be enrolled from academic medicine, community health network, and insurance payer study sites. Participants are randomized 1:1 to either 1-session Empowered Relief or 8-session CBT, with both treatments delivered online to groups. Mixed-model repeated measures and intention-to-treat analytic approaches will be used to test comparative effectiveness aims from baseline to 3 months after treatment (the primary end point). Multiple primary outcomes are pain intensity and pain interference; priority secondary outcomes are sleep disturbance, pain catastrophizing, pain bothersomeness, and anxiety; and other secondary outcomes are satisfaction with roles and responsibilities and global impression of change, anger, fatigue, and depression. Durability of effects will be tested at 6 months after treatment. Empowered Relief is hypothesized to have superior treatment completion and adherence and lower treatment burden ratings than CBT. In exploratory analyses, we will compare health care use through medical record and claims data 3 months prior to enrollment to the last 3 study months, hypothesizing reduced noninferiority in reduced use. The study also incorporates a multilevel patient engagement infrastructure to improve accessibility, recruitment, and study relevance. Results As of May 2026, we have enrolled 130 participants. Enrollment is anticipated to end in November 2026, with treatments completed by April 2027 and full analyses completed by February 2028. Conclusions Lupus PROGRESS will provide real-world pragmatic evidence on whether a 1-session online group skill-based treatment is noninferior to 8-session CBT. Results from this patient-centered study will inform more accessible, equitable, and patient-centered chronic pain care for people living with lupus. Trial Registration ClinicalTrials.gov NCT05612750; https://clinicaltrials.gov/study/NCT05612750 International Registered Report Identifier (IRRID) DERR1-10.2196/100104

To estimate the prevalence of insomnia disorder and insomnia symptoms, explore risk factors for insomnia disorder, and characterize sleep at 6 weeks postpartum. Following IRB approval, adults who delivered a live infant at two academic US hospitals were prospectively recruited with a pre-specified cross-sectional analysis planned at 6 weeks postpartum, evaluating new sleep disturbance (SD) and sleep-related impairment (SRI) surveys. Participants were invited to complete surveys (Bergen Insomnia Scale (BIS), PROMIS SD, and SRI), and a structured clinical interview for sleep disorders (SCISD-R, the diagnostic standard), at 6 weeks postpartum, until 150 interviews were completed. Demographic and clinical variables were collected. Primary outcome was prevalence of insomnia disorder by SCISD-R; secondary outcomes were sleep characteristics and survey scores, clinical and sociodemographic factors associated with insomnia disorder, and exploratory evaluation of the diagnostic accuracy of BIS, PROMIS SD, and SRI for insomnia disorder identified by SCISD-R. Associations were assessed using univariate odds ratios and 95

Background:Chronic pain is associated with impaired muscle health, but whether these changes reflect site-specific factors, broader systemic factors, or both remains unclear. The purpose of this study is to determine whether normative markers of muscle health derived from MRI show site-specific patterns in chronic pain. Methods:UK Biobank participants who underwent whole-body MRI from 2006 to 2010 were included in this retrospective cross-sectional study. The MuscleMap Toolbox quantified volume and intramuscular fat (IMF) in 42 muscles of the abdomen, pelvis, and thigh. Normative models trained on a no pain group generated muscle-specific deviations from normal (i.e., Z-scores) for single- and multi-site chronic and acute pain. Results:Of 17,843 participants, the primary site-specific analysis included 9,704 no pain, 885 single-site chronic back pain (CBP), 438 single-site chronic hip pain (CHP), and 1,315 single-site chronic knee pain (CKP) participants (n=12,342; mean age 63.7±7.5 years; 52.7% female). Additional analyses included single-site chronic neck/shoulder pain, acute pain, and multi-site chronic pain groups. In CBP, deviations were localized to abdominal muscles, with decreased volume in 6/8 and increased IMF in 6/8. In CHP, deviations were broad, with decreased volume in 3/8 of the abdominal and 14/26 of the thigh muscles, and increased IMF in 6/8 of the abdominal, 5/8 of the pelvic, and 4/26 of the thigh muscles. In CKP, deviations were localized to thigh muscles, with decreased volume in 8/26 and increased IMF in 6/26. Acute pain groups showed no significant differences except for decreased volume in one thigh muscle in acute knee pain. With each additional chronic pain site, volume decreased (β=-.078;IQR:-0.100-0.051), and IMF increased (β=.085;IQR:0.066-0.101). Combined Z-scores classified chronic pain groups better than chance (accuracy: 48.6%;p<.001), but not acute pain groups (accuracy: 39.0%;p=.20). Conclusions:Whole-body MRI combined with AI-driven muscle segmentation and normative modeling revealed site-specific patterns of muscle health in single-site chronic pain.

Postpartum sleep is a unique construct, and existing sleep patient-reported outcome measures (PROMs) do not adequately address some of its fundamental domains. We aimed to develop postpartum-specific extension items to the PROMIS Sleep Disturbance (SD) and Sleep Related Impairment (SRI) item banks. The postpartum-specific SD and SRI items were developed to add to the existing PROMIS SD and SRI item banks. Postpartum-specific PROMIS items were generated based on findings from literature characterizing postpartum sleep, including systematic reviews and qualitative interviews with patients and experts from diverse specialties. The candidate items were subsequently iteratively adapted and selected through a modified Delphi process involving a panel of 21 stakeholders including experts in obstetrics, sleep, psychiatry, patients and partner representatives. Items achieving consensus with ≥ 70

Exogenous opioids that activate μ-opioid receptors (MORs) in nociceptive circuits mediate transient pain relief lasting minutes to hours but have more limited utility for treating chronic pain. By comparison, electrical or magnetic stimulation of the motor cortex can induce pain relief lasting weeks, for which the underlying mechanisms have remained unclear. Here we report an unconventional role for endogenous opioidergic signaling in the rapid induction of long-lasting analgesia from motor cortical stimulation, which triggers opioid-peptide-dependent neural plasticity in the rostral ventromedial medulla (RVM), a key node in the brain's descending pain control pathways. To dissect the circuit and cellular bases for these effects, we created a miniaturized, millimeter-sized device allowing focal, non-invasive transcranial magnetic stimulation (TMS) of the mouse motor cortex. In mice with chronic neuropathic pain, reflexive and affective pain behaviors diminished for 1-2 weeks after one session of TMS treatment. Chemogenetic and optogenetic manipulations showed that motor cortical layer 5 pyramidal neurons with axonal projections to the RVM mediated TMS-induced pain relief. High-density electrophysiological recordings revealed that TMS treatment shifted the balance of RVM activity between pain-ON and pain-OFF neurons to a state promoting greater suppression of pain. Genetic and neuropharmacological manipulations revealed that NMDA-receptor-dependent signaling and MOR activation by endogenous opioid peptides in the RVM jointly mediate the long-lasting analgesia induced by a transient bout of TMS. Strikingly, enkephalinase inhibition in the RVM during TMS treatment enhanced the amplitude and duration of analgesia, showing that transiently boosting endogenous opioidergic signaling during TMS increases analgesia-conferring plasticity. In accord, re-analyses of data from human subjects with chronic pain support the idea that opioid administration amplifies analgesia from motor cortical TMS. Overall, our results showcase miniaturized TMS devices as versatile tools for basic and translational neuroscience and detail a hybrid, long-range neural network and NMDA- and opioid-receptor-dependent plasticity mechanism for durable pain relief. These findings point the way to mechanistically grounded, synergistic neurostimulation and drug therapies for brain diseases and disorders that jointly target neural circuit and molecular signaling pathways.