A Transcriptomics Analysis of the Regulation of Lens Fiber Cell Differentiation in the Absence of FGFRs and PTEN.

Adding 50% vitreous humor to the media surrounding lens explants induces fiber cell differentiation and a significant immune/inflammatory response. While Fgfr loss blocks differentiation in lens epithelial explants, this blockage is partially reversed by deleting Pten. To investigate the functions of the Fgfrs and Pten during lens fiber cell differentiation, we utilized a lens epithelial explant system and conducted RNA sequencing on vitreous humor-exposed explants lacking Fgfrs, or Pten or both Fgfrs and Pten. We found that Fgfr loss impairs both vitreous-induced differentiation and inflammation while the additional loss of Pten restores these responses. Furthermore, transcriptomic analysis suggested that PDGFR-signaling in FGFR-deficient explants is required to mediate the rescue of vitreous-induced fiber differentiation in explants lacking both Fgfrs and Pten. The blockage of ß-crystallin induction in explants lacking both Fgfrs and Pten in the presence of a PDGFR inhibitor supports this hypothesis. Our findings demonstrate that a wide array of genes associated with fiber cell differentiation are downstream of FGFR-signaling and that the vitreous-induced immune responses also depend on FGFR-signaling. Our data also demonstrate that many of the vitreous-induced gene-expression changes in Fgfr-deficient explants are rescued in explants lacking both Fgfrs and Pten.

AAV gene replacement therapy for treating MPS IIIC: Facilitating bystander effects via EV-mRNA cargo.

MPS IIIC is a lysosomal storage disease caused by mutations in heparan-α-glucosaminide N-acetyltransferase (HGSNAT), for which no treatment is available. Because HGSNAT is a trans-lysosomal-membrane protein, gene therapy for MPS IIIC needs to transduce as many cells as possible for maximal benefits. All cells continuously release extracellular vesicles (EVs) and communicate by exchanging biomolecules via EV trafficking. To address the unmet need, we developed a rAAV-hHGSNATEV vector with an EV-mRNA-packaging signal in the 3'UTR to facilitate bystander effects, and tested it in an in vitro MPS IIIC model. In human MPS IIIC cells, rAAV-hHGSNATEV enhanced HGSNAT mRNA and protein expression, EV-hHGSNAT-mRNA packaging, and cleared GAG storage. Importantly, incubation with EVs led to hHGSNAT protein expression and GAG contents clearance in recipient MPS IIIC cells. Further, rAAV-hHGSNATEV transduction led to the reduction of pathological EVs in MPS IIIC cells to normal levels, suggesting broader therapeutic benefits. These data demonstrate that incorporating the EV-mRNA-packaging signal into a rAAV-hHGSNAT vector enhances EV packaging of hHGSNAT-mRNA, which can be transported to non-transduced cells and translated into functional rHGSNAT protein, facilitating cross-correction of disease pathology. This study supports the therapeutic potential of rAAVEV for MPS IIIC, and broad diseases, without having to transduce every cell.

Using a Novel, Subconjunctival, Sustained-Release Mitomycin C Formulation in a Rabbit Model of Filtration Surgery with Gel Stent Implantation.

Purpose: To investigate gel stent implantation with and without intraoperative sustained-release mitomycin C (MMC SR) in a rabbit model for gel stent implantation, and to examine aqueous humor outflow (AHO) postimplantation. Methods: Four groups of rabbits were included. Group 1 was untreated (control). Groups 2, 3, and 4 received the gel stent without MMC, with MMC solution (subconjunctival injection), and with MMC SR (subconjunctival injection), respectively. Intraocular pressure (IOP) and AHO were assessed via tonometry and indocyanine green-based angiography, respectively. The main efficacy measure was change in IOP from baseline. Results: Following gel stent implantation, Groups 2, 3, and 4 maintained ≥20% IOP reduction (response) for a median duration of 1 week, 6.5 weeks, and 30 weeks, respectively. Angiography showed normal aqueous humor drainage (Group 1) beginning at the perilimbal trabecular plexus and continuing posteriorly to episcleral outflow vessels. Following implantation, drainage occurred preferentially and directly into the subconjunctival bleb. Conclusions: Gel stent implantation with MMC SR was most effective in achieving sustained, long-term IOP reduction in the rabbit model, compared with implantation with or without MMC solution. Bleb presence and the postimplantation aqueous angiography results indicated redirection of the AHO to the subconjunctival vasculature and presumed lymphatics, suggesting efficient glaucoma filtration to lower IOP in this model. This rabbit model and aqueous angiography may help refine understanding of the mechanism of action of minimally invasive glaucoma surgeries and ultimately translate to improved surgical devices and procedures for patients with glaucoma.

Attitudes and barriers towards deprescribing in older patients experiencing polypharmacy: a narrative review.

Polypharmacy, commonly defined as ≥5 medications, is a rising public health concern due to its many risks of harm. One commonly recommended strategy to address polypharmacy is medication reviews, with subsequent deprescription of inappropriate medications. In this review, we explore the intersection of older age, polypharmacy, and deprescribing in a contemporary context by appraising the published literature (2012-2022) to identify articles that included new primary data on deprescribing medications in patients aged ≥65 years currently taking ≥5 medications. We found 31 articles were found which describe the current perceptions of clinicians towards deprescribing, the identified barriers, key enabling factors, and future directions in approaching deprescribing. Currently, clinicians believe that deprescribing is a complex process, and despite the majority of clinicians reporting feeling comfortable in deprescribing, fewer engage with this process regularly. Common barriers cited include a lack of knowledge and training around the deprescribing process, a lack of time, a breakdown in communication, perceived 'abandonment of care', fear of adverse consequences, and resistance from patients and/or their carers. Common enabling factors of deprescribing include recognition of key opportunities to instigate this process, regular medication reviews, improving lines of communication, education of both patients and clinicians and a multidisciplinary approach towards patient care. Addressing polypharmacy requires a nuanced approach in a generally complex group of patients. Key strategies to reducing the risks of polypharmacy include education of patients and clinicians, in addition to improving communication between healthcare providers in a multidisciplinary approach.

Polypharmacy in older patients presenting to a tertiary regional health service: identifying correlations between demographics, presentations and length of stay.

This study aimed to describe hospital admissions in patients experiencing polypharmacy and evaluate the effects of demographic factors on length of stay (LOS) and polypharmacy. We found that increasing age is associated with increasing polypharmacy rates but decreasing LOS. Females were more likely to experience higher rates of polypharmacy, but males were more likely to have longer LOS. First Nations peoples had higher rates of polypharmacy and longer LOS. Future projects investigating deprescribing methods are critical.

Patient perspectives on the use of indwelling pleural catheters in malignant pleural effusions.

BACKGROUND: Indwelling pleural catheters are an effective treatment option for patients with malignant pleural effusions. Despite their popularity, there remains a paucity of data on the patient experience and key patient-centred outcomes. OBJECTIVE: To investigate the experience of patients receiving an indwelling pleural catheter to better inform and identify potential areas for improvement in care. METHODS: This was a multicentre survey study at three academic, tertiary-care centres in Canada. Patients with a diagnosis of malignant pleural effusion who had an indwelling pleural catheter inserted were included. An adapted questionnaire specific to indwelling pleural catheters was used with responses recorded on a 4-point Likert scale. Patients completed the questionnaire in-person or by phone at 2-week and 3-month follow-up appointments. RESULTS: A total of 105 patients were enrolled in the study with 84 patients included in the final analysis. At the 2-week follow-up, patient-reported improvements in dyspnoea and quality of life from indwelling pleural catheter were high at 93% and 87%, respectively. The predominant issues identified were discomfort at time of insertion (58%), itching (49%), difficulty with sleeping (39%), discomfort with home drainage (36%) and the pleural catheter reminding patients of their disease (63%). Avoiding hospitalisation for the management of dyspnoea was important to 95% of patients. Findings were similar at 3 months. CONCLUSIONS: Indwelling pleural catheters are an effective intervention to directly improve dyspnoea and quality of life but have important disadvantages for some; clinicians and patients should be aware of these when making an informed decision regarding treatment.

HPV Infection and Vaccination: A Question and Answer Guide for School Nurses.

School nurses frequently interact with school-age children and their parents/guardians regarding vaccinations. As a trusted source of information, the school nurse is in a unique position to share vaccine information with parents/guardians and school-age children that may dispel myths and, consequently, improve vaccination rates. Nevertheless, some parents/guardians are still reluctant to vaccinate their school-age children against Human Papilloma Virus (HPV) for a variety of reasons. Common barriers to HPV vaccination include a lack of understanding of the vaccine's purpose, concerns regarding the vaccine's safety, and insufficient recommendation from healthcare workers. However, school nurses have many duties in addition to ensuring vaccine compliance. School nurses may have difficulty remaining up-to-date on evidence-based answers to parents'/guardians' questions about HPV vaccine. Therefore, the purpose of this article is to provide school nurses with a quick reference question and answer guide to parents'/guardians' common HPV-related vaccination questions.

Intercostal Lung Hernia Following Deep Inferior Epigastric Perforator Reconstruction.

Acquired lung hernias typically result from trauma or intra-thoracic surgery is defined as the protrusion of lung parenchyma beyond the anatomic boundaries of the thoracic wall. A 40-year-old woman underwent deep inferior epigastric perforator (DIEP) breast reconstruction following her mastectomies. Post-operatively, she returned to the emergency department with severe chest pain, shortness of breath, and localized chest swelling. CT angiography demonstrated intercostal right lung hernia with concern for incarceration. She returned emergently to the operating room. The lung was reduced, but the flap was ultimately determined to be nonviable and was removed. Post-operative course was uneventful and the patient recovered well. Intercostal lung hernia is an uncommon clinical entity that has not previously been described as a complication of DIEP breast reconstruction. Its development is associated with significant morbidity including flap loss in this case. Early recognition of this rare complication is essential to avoid more severe sequelae of tissue ischemia.

Association between underlying autoimmune disease and small aneurysm size at rupture.

OBJECTIVE: Although the role of inflammation in the development of aneurysms is established, less is known about the development of intracranial aneurysms in the setting of underlying autoimmune disease. The underlying systemic inflammatory characteristics of disorders such as systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome may influence the development of intracranial aneurysms through common inflammatory pathways. The authors hypothesized that there is an association between underlying autoimmune disease and aneurysm growth and rupture. METHODS: Medical records of patients who underwent cerebral angiography between August 2018 and August 2021 were manually reviewed. Autoimmune diseases as defined for this study are those known to have systemic inflammatory effects on the central nervous system or multiple other organ systems. Statistical analysis, including construction of multivariable linear and logistic regression models, was performed using R version 4.1.0. RESULTS: Chart review identified 190 patients with 469 ruptured and unruptured saccular intracranial aneurysms. There were 31 patients with 44 aneurysms identified as having an autoimmune disease. The mean size of a ruptured aneurysm was significantly smaller among patients with autoimmune disease compared with patients without autoimmune disease (4.14 mm vs 5.34 mm, p = 0.03). The multivariate logistic regression model did not identify any significant association between rupture and autoimmune disease when controlling for other variables (p = 0.49). In the multivariate linear regression model, autoimmune disease was still significantly associated with a smaller size at rupture (p = 0.04), and smoking was associated with a larger size at rupture (p = 0.03) when controlling for other variables. A second multivariate logistic regression model found autoimmune disease to be independently associated with rupture at a size smaller than 7 mm (p = 0.02), while smoking was independently associated with rupture at a size larger than 7 mm (p = 0.01). CONCLUSIONS: Autoimmune disease is associated with a smaller aneurysm size at rupture, although it is not associated with rupture itself. This association may be due to inflammatory pathways that are common to autoimmune diseases as well as aneurysm wall development. Although the authors were unable to identify any association between rupture status and the presence of autoimmune disease, the association between smaller size at rupture and autoimmune disease warrants further studies, as autoimmune disease may influence the trajectory of aneurysm development and the decision to treat.

Hand size estimates of fibromyalgia patients are associated with clinical and experimental pain.

INTRODUCTION: Simply inspecting one's own body can reduce clinical pain and magnification of body parts can increase analgesia. Thus, body perceptions seem to play an important role for analgesia. Conversely, pain may also affect bodily perceptions. Therefore, we evaluated the effects of clinical and/or experimental pain on perceived hand size in fibromyalgia patients (FM) and healthy controls (HC). METHODS: To investigate the effects of chronic and/or acute pain on size perception we compared hand size estimates of 35 HC and 32 FM patients at baseline and during tonic mechanical pain stimuli applied to one ear lobe. Mechanical stimuli were adjusted for each individual pain sensitivity to achieve a rating of 4 ± 1 VAS (0-10) units. Photographs of each subject's hands were digitally manipulated to produce a monotonic series of 5 images larger and 6 smaller than actual size which were then presented to the participants in ascending and descending order (total number of images: 12). RESULTS: FM and HC participants' clinical pain ratings at baseline were 3.3 (3.1) and .3 (.8) VAS units, respectively. At baseline, FM participants selected significantly smaller hand images than HC as representative of their actual size (p < .02). During application of tonic experimental pain, the image size chosen to represent their actual hand size decreased significantly in FM participants and HC (p < .001) but this decrease was not different between groups (p > .05). Hand size estimates of FM participants correlated negatively with their clinical pain ratings (p < .04). CONCLUSION: The decreased hand size perception of FM patients and HC was associated with their clinical and/or experimental pain, supporting the hypothesis that pain can result in visual body distortions.

Exclusively endoscopic management of complicated pineal cysts in young children: Definitive treatment through single burr-hole technique.

Background: The management of complicated symptomatic pineal cysts in the pediatric population is challenging and variable. Surgical management may include treatment of hydrocephalus alone, or direct treatment of the cyst with or without direct hydrocephalus management. This is typically done through craniotomy-based microsurgical approaches to the pineal region or an endoscopic transventricular approach. Methods: We present a stepwise minimally invasive technique to treat complicated pineal cysts in young children associated with an obstructive hydrocephalus in a single procedure through third ventriculostomy combined with an intraventricular marsupialization of the pineal cyst through a single burr-hole using stereotactic navigation. Results: Two young patients with over 2 years of follow-up have done well without complication using this technique. Other literature reports for complex pineal cysts in pediatric patients are reviewed and this technique is not previously described for this population. Conclusion: Endoscopic third ventriculostomy and cyst marsupialization using a single burr-hole and stereotactic navigation for symptomatic or enlarging pineal cysts in children allow for minimally invasive management, a rapid recovery, short hospital stay, and durable outcome owed to redundant CSF flow pathways.

Accrual and retention of diverse patients in psychosocial cancer clinical trials.

Background: Minority and older adult patients remain underrepresented in cancer clinical trials (CCTs). The current study sought to examine sociodemographic inequities in CCT interest, eligibility, enrollment, decline motivation, and attrition across two psychosocial CCTs for gynecologic, gastrointestinal, and thoracic cancers. Methods: Patients were approached for recruitment to one of two interventions: (1) a randomized control trial (RCT) examining effects of a cognitive-behavioral intervention targeting sleep, pain, mood, cytokines, and cortisol following surgery, or (2) a yoga intervention to determine its feasibility, acceptability, and effects on mitigating distress. Prospective RCT participants were queried about interest and screened for eligibility. All eligible patients across trials were offered enrollment. Patients who declined yoga intervention enrollment provided reasons for decline. Sociodemographic predictors of enrollment decisions and attrition were explored. Results: No sociodemographic differences in RCT interest were observed, and older patients were more likely to be ineligible. Eligible Hispanic patients across trials were significantly more likely to enroll than non-Hispanic patients. Sociodemographic factors predicted differences in decline motivation. In one trial, individuals originating from more urban areas were more likely to prematurely discontinue participation. Discussion: These results corroborate evidence of no significant differences in CCT interest across minority groups, with older adults less likely to fulfill eligibility criteria. While absolute Hispanic enrollment was modest, Hispanic patients were more likely to enroll relative to non-Hispanic patients. Additional sociodemographic trends were noted in decline motivation and geographical prediction of attrition. Further investigation is necessary to better understand inequities, barriers, and best recruitment practices for representative CCTs.

Intraocular Pressure-Lowering Efficacy of a Sustained-Release Bimatoprost Implant in Dog Eyes Pretreated with Selective Laser Trabeculoplasty.

Purpose: To assess the intraocular pressure (IOP)-lowering effect of a biodegradable bimatoprost implant following selective laser trabeculoplasty (SLT) in a canine model. Methods: Unilateral SLT was performed in 11 normotensive, treatment-naive beagle dogs. IOP was measured at baseline (pre-SLT) and weekly post-SLT (≤10 weeks). After IOP returned to baseline or at 10 weeks (whichever occurred first), a sustained-release bimatoprost implant was administered bilaterally in the anterior chamber of each animal. IOP was measured weekly for 4 weeks and then every 2 weeks up to week 42. Results: The main outcomes included the IOP change (%) from baseline, calculated in both eyes in the overall population, SLT responder subgroup (defined by peak IOP reduction from baseline ≥3 mmHg or ≥15% for >1 week post-SLT), and SLT nonresponder subgroup (defined by peak IOP reduction from baseline <3 mmHg or <15%). The bimatoprost implant lowered IOP similarly in both the SLT-treated and fellow SLT-naive eyes. Following bimatoprost implant administration, the mean (standard deviation [SD]) peak IOP reduction from baseline was 34.4% (8.5%) in SLT-treated eyes and 35.7% (5.9%) in fellow SLT-naive eyes. The bimatoprost implant lowered IOP comparably (P > 0.17) in eyes that responded to SLT (mean [SD] peak IOP reduction, 34.6% [10.7%]; n = 6) and those that did not (mean [SD] peak IOP reduction, 34.1% [6.1%]; n = 5). Conclusion: The bimatoprost implant effectively lowered IOP in eyes pretreated with SLT, regardless of response to SLT. The current data suggest that eyes previously treated with SLT can still benefit from the intracameral bimatoprost implant.

Neural activation changes in response to pain following cognitive behavioral therapy for patients with comorbid fibromyalgia and insomnia: a pilot study.

STUDY OBJECTIVES: To examine whether cognitive behavioral treatments for insomnia (CBT-I) and pain (CBT-P) lead to neural activation changes in response to pain in fibromyalgia. METHODS: Thirty-two patients with fibromyalgia (mean age = 55.9, standard deviation = 12.2) underwent an experimental pain protocol during functional magnetic resonance imaging and completed 14-day diaries assessing total wake time, total sleep time, and pain intensity before and after CBT-I, CBT-P, or waitlist control. Random effects analysis of covariance identified regions with significant group (CBT-I, CBT-P, waitlist control) by time (baseline, post-treatment) interactions in blood oxygen level-dependent response to pain. Linear regressions using residualized change scores examined how changes in total wake time, total sleep time, and pain intensity were related to activation (blood oxygen level-dependent) changes. RESULTS: Twelve regions exhibited small to moderate effects with significant interactions Ps < .00; right hemisphere: inferior frontal, middle occipital, and superior temporal gyri, insula, lentiform nucleus; left hemisphere: angular, superior temporal, midfrontal, inferior occipital, midtemporal, and inferior frontal gyri. Blood oxygen level-dependent response to pain decreased in 8 regions following CBT-I, and in 3 regions following CBT-P (CBT-I effects > CBT-P). Blood oxygen level-dependent response also increased in 3 regions following CBT-P and in 6 regions following waitlist control. Improved total wake time and/or total sleep time, not pain intensity, predicted decreased blood oxygen level-dependence in 7 regions (Ps < .05), accounting for 18%-47% of the variance. CONCLUSIONS: CBT-I prompted greater decreases in neural activation in response to pain across more regions associated with pain and sleep processing than CBT-P. Reported sleep improvements may underlie those decreases. Future research examining the longer-term impact of CBT-I and improved sleep on central pain and sleep mechanisms is warranted. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Title: Sleep and Pain Interventions in Fibromyalgia (SPIN); Identifier: NCT02001077; URL: https://clinicaltrials.gov/ct2/show/NCT02001077. CITATION: McCrae CS, Craggs JG, Curtis AF, et al. Neural activation changes in response to pain following cognitive behavioral therapy for patients with comorbid fibromyalgia and insomnia: a pilot study. J Clin Sleep Med. 2022;18(1):203-215.

Impacts of Cognitive Behavioral Therapy for Insomnia and Pain on Sleep in Women with Gynecologic Malignancies: A Randomized Controlled Trial.

Insomnia is an adverse cancer outcome impacting mood, pain, quality of life, and mortality in cancer patients. Cognitive Behavioral Therapy (CBT) is an evidence-based treatment for diverse psychophysiological disorders, including pain and insomnia. Primarily studied in breast cancer, there is limited research on CBT within gynecology oncology. This study examined CBT effects on subjective and behavioral sleep outcomes: Sleep Efficiency (SE), Sleep Quality (SQ), Total Wake Time (TWT), Sleep Onset Latency (SOL), and Wake After Sleep Onset (WASO). Thirty-five women with insomnia status/post-surgery for gynecologic cancer were randomized to CBT for insomnia and pain (CBTi.p., N = 18) or Psychoeducation (N = 17). Sleep was assessed via sleep diaries and wrist-worn actigraphy at baseline (T1), post-intervention (T2), and two-month follow-up (T3). Intent-to-treat analyses utilizing mixed linear modeling examined longitudinal group differences on sleep controlling for age and advanced cancer. All participants demonstrated improved (1) subjective SE (0.5, p < .01), SOL (-1.2, p < .01), TWT (-1.2, p < .01), and (2) behavioral SE (0.1, p = .02), TWT (-1.2, p = .03), WASO (-0.8, p < .01) across time. Group-level time trends were indicative of higher subjective SE (6.8, p = .02), lower TWT (-40.3, p = .01), and lower SOL (-13.0, p = .05) in CBTi.p. compared to Psychoeducation. Supplemental analyses examining clinical significance and acute treatment effects demonstrated clinical improvements in SE (T1), TWT (T2, T3), and SOL (T3). Remaining effects were not significant. Despite lacking power to detect interaction effects, CBTi.p. clinically improved sleep in women with gynecologic cancers and insomnia during the active treatment phase. Future research will focus on developing larger trials within underserved populations.

Transcriptomic analysis of human skin wound healing and rejuvenation following ablative fractional laser treatment.

Ablative fractional laser treatment is considered the gold standard for skin rejuvenation. In order to understand how fractional laser works to rejuvenate skin, we performed microarray profiling on skin biopsies to identify temporal and dose-response changes in gene expression following fractional laser treatment. The backs of 14 women were treated with ablative fractional laser (Fraxel®) and 4 mm punch biopsies were collected from an untreated site and at the treated sites 1, 3, 7, 14, 21 and 28 days after the single treatment. In addition, in order to understand the effect that multiple fractional laser treatments have on skin rejuvenation, several sites were treated sequentially with either 1, 2, 3, or 4 treatments (with 28 days between treatments) followed by the collection of 4 mm punch biopsies. RNA was extracted from the biopsies, analyzed using Affymetrix U219 chips and gene expression was compared between untreated and treated sites. We observed dramatic changes in gene expression as early as 1 day after fractional laser treatment with changes remaining elevated even after 1 month. Analysis of individual genes demonstrated significant and time related changes in inflammatory, epidermal, and dermal genes, with dermal genes linked to extracellular matrix formation changing at later time points following fractional laser treatment. When comparing the age-related changes in skin gene expression to those induced by fractional laser, it was observed that fractional laser treatment reverses many of the changes in the aging gene expression. Finally, multiple fractional laser treatments, which cover different regions of a treatment area, resulted in a sustained or increased dermal remodeling response, with many genes either differentially regulated or continuously upregulated, supporting previous observations that maximal skin rejuvenation requires multiple fractional laser treatments. In conclusion, fractional laser treatment of human skin activates a number of biological processes involved in wound healing and tissue regeneration.

Fibromyalgia Patients Are Not Only Hypersensitive to Painful Stimuli But Also to Acoustic Stimuli.

Fibromyalgia is a chronic widespread pain syndrome associated with hypersensitivity to nociceptive stimuli. This increased sensitivity of FM patients has been associated with central sensitization of dorsal horn neurons. Increasing evidence, however, suggests that the mechanisms of FM hypersensitivity not only affect pain but include light, smell, and sound. We hypothesized that supraspinal augmentation of sensory input including sound represent a hallmark of FM. We tested 23 FM patients and 28 healthy controls (HC) for sensory augmentation of nociceptive and non-nociceptive sensations: For assessment of nociceptive augmentation we used sensitivity adjusted mechanical and heat ramp & hold stimuli and for assessment of sound augmentation, we applied wideband noise stimuli using a random-staircase design. Quantitative sensory testing demonstrated increased heat and mechanical pain sensitivity in FM participants (P < .001). The sound pressures needed to report mild, moderate, and intense sound levels were significantly lower in FM compared to HC (P < .001), consistent with auditory augmentation. FM patients are not only augmenting noxious sensations but also sound, suggesting that FM augmentation mechanisms are not only operant in the spinal cord but also in the brain. Whether the central nervous system mechanisms for auditory and nociceptive augmentation are similar, needs to be determined in future studies. PERSPECTIVE: This study presents QST evidence that the hypersensitivity of FM patients is not limited to painful stimuli but also to innocuous stimuli like sound. Our results suggest that abnormal brain mechanisms may be responsible for the increased sensitivity of FM patients.