Plasma proteomic profiles of pain subtypes in adolescents and young adults with endometriosis.

STUDY QUESTION: What are the similarities and differences in the systemic proteomic profiles by endometriosis-associated pain subtypes among adolescents and young adults with endometriosis? SUMMARY ANSWER: Endometriosis-associated pain subtypes exhibited distinct plasma proteomic profiles. WHAT IS KNOWN ALREADY: Endometriosis patients, especially those diagnosed in adolescents and young adults, are often plagued by various pain symptoms. However, it is not clear what biological processes underlie this heterogeneity. STUDY DESIGN, SIZE, DURATION: We conducted a cross-sectional analysis using data and plasma samples from 142 adolescent or young adult participants of the Women's Health Study: From Adolescence to Adulthood cohort with laparoscopically confirmed endometriosis. PARTICIPANTS/MATERIALS, SETTING, METHODS: We measured 1305 plasma protein levels by SomaScan. We classified self-reported endometriosis-associated pain into subtypes of dysmenorrhea, acyclic pelvic pain, life impacting pelvic pain, bladder pain, bowel pain, and widespread pain phenotype. We used logistic regression to calculate the odds ratios and 95% confidence intervals for differentially expressed proteins, adjusting for age, BMI, fasting status, and hormone use at blood draw. Ingenuity Pathway Analysis identified enriched biological pathways. MAIN RESULTS AND THE ROLE OF CHANCE: Our study population consisted mainly of adolescents and young adults (mean age at blood draw = 18 years), with nearly all (97%) scored as rASRM stage I/II at laparoscopic diagnosis of endometriosis, which is a common clinical presentation of endometriosis diagnosed at a younger age. Pain subtypes exhibited distinct plasma proteomic profiles. Multiple cell movement pathways were downregulated in cases with severe dysmenorrhea and life impacting pelvic pain compared to those without (P < 7.5×10-15). Endometriosis cases with acyclic pelvic pain had upregulation of immune cell adhesion pathways (P < 9.0×10-9), while those with bladder pain had upregulation of immune cell migration (P < 3.7×10-8) and those with bowel pain had downregulation (P < 6.5×10-7) of the immune cell migration pathways compared to those without. Having a wide-spread pain phenotype involved downregulation of multiple immune pathways (P < 8.0×10-10). LIMITATIONS, REASONS FOR CAUTION: Our study was limited by the lack of an independent validation cohort. We were also only able to explore any presence of a pain subtype and could not evaluate multiple combinations by pain subtypes. Further mechanistic studies are warranted to elucidate the differences in pathophysiology by endometriosis-pain subtype. WIDER IMPLICATIONS OF THE FINDINGS: The observed variation in plasma protein profiles by pain subtypes suggests different underlying molecular mechanisms, highlighting the need for potential consideration of pain subtypes for effectively treating endometriosis patients presenting with various pain symptoms. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Department of Defense W81XWH1910318 and the 2017 Boston Center for Endometriosis Trainee Award. Financial support for establishment of and data collection within the A2A cohort were provided by the J. Willard and Alice S. Marriott Foundation. N.S., A.F.V., S.A.M., and K.L.T. have received funding from the Marriott Family Foundation. C.B.S. is funded by an R35 MIRA Award from NIGMS (5R35GM142676). S.A.M. and K.L.T. are supported by NICHD R01HD094842. S.A.M. reports serving as an advisory board member for AbbVie and Roche, Field Chief Editor for Frontiers in Reproductive Health, personal fees from Abbott for roundtable participation; none of these are related to this study. Other authors report no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

The mediating effect of social functioning on the relationship between catastrophizing and pain among patients with chronic low back pain.

OBJECTIVE: Pain catastrophizing can be characterized as an interpersonal form of coping used to elicit support or empathy from others. Despite intentions of increasing support, catastrophizing can impair social functioning. While considerable work has addressed the relationship between catastrophizing and pain, limited empirical work has examined this relationship within a social context. First, we examined the role of catastrophizing as a potential contributor to group differences (chronic low back pain [cLBP] vs pain-free controls) in social functioning. Then we conducted a follow-up, exploratory analysis to examine the relationships between catastrophizing, social functioning, and pain within the subgroup of participants with cLBP. METHODS: In this observational study, participants with cLBP (N = 62) and pain-free controls (N = 79) completed validated measures of pain, social functioning, and pain catastrophizing. A mediation analysis was conducted to examine whether catastrophizing mediated group differences (cLBP vs controls) in social functioning. A follow-up, exploratory mediation analysis then tested whether social functioning mediated the association between catastrophizing and pain within the subgroup of cLBP participants. RESULTS: Participants with cLBP reported higher levels of pain, impaired social functioning, and higher catastrophizing compared to pain-free controls. Catastrophizing partially mediated the group difference in impaired social functioning. Additionally, social functioning mediated the association between higher catastrophizing and greater pain within the subgroup of cLBP participants. CONCLUSIONS: We showed that impaired social functioning was driving the relationship between higher pain catastrophizing and worse pain among participants with cLBP. Interventions, such as cognitive behavioral therapy, should address catastrophizing in individuals with cLBP, while simultaneously improving social functioning.

Pilot Investigation of Somatosensory Functioning and Pain Catastrophizing in Pediatric Spinal Fusion Surgery.

PURPOSE: Chronic post-surgical pain (CPSP) is a significant concern and contributes to the opioid epidemic; however, little is known about CPSP in young people. DESIGN: This prospective study aimed to identify sensory, psychological, and demographic factors that may increase the risk of CPSP after spinal fusion surgery for children and adolescents with idiopathic scoliosis. METHODS: 32 children and adolescents from two children's hospitals completed quantitative sensory testing (QST) and the Pain Catastrophizing Scale Child (PCS-C) pre-and 4-6 months post spinal fusion surgery. Between-group differences were assessed using an independent samples t-test. Pearson's correlations and stepwise linear regression were used to assess the relationship between variables at both time points. RESULTS: 56% of patients endorsed pain post-surgery. They were more sensitive tomechanical detection on both a control non-pain site (r = -2.87, p = .004) and the back (r = -1.83, p = .04), as well as pressure pain (r=-2.37, p = .01) on the back. This group also reported worse pain scores pre-surgery. Pre-surgery helplessness positively correlated with preoperative pain (r = .67 p < .001), and age was negatively correlated with the post-surgical catastrophizing total score (r =-.39, p = .05), suggesting that younger patients endorsed more pain-related worry after surgery. CONCLUSIONS: Patients who present with pain during their preoperative appointment may need to be monitored with increased vigilance throughout the perioperative period, possibly with bedside QST and psychological questionnaires, which nurses could administer. Biobehavioral interventions targeting pain intensity and feelings of helplessness and anxiety during the preoperative period may alleviate the transition to CPSP.

Gender interactions on Twitter and medical education: how is nephrology doing?

Gender inequities negatively impact productivity and career advancement for women. Social media platforms like Twitter can be used to achieve greater parity and address underrepresentation by providing a medium for education, research and mentorship, however, it is unknown how it may contribute to gender inequity. Our aim was to examine gender interactions during a nephrology medical conference.

Alterations in the structure and function of the brain in adolescents with new daily persistent headache: A pilot MRI study.

OBJECTIVE: The purpose of this study was to explore brain morphological and functional connectivity alterations in adolescents with new daily persistent headache (NDPH) compared to pain-free, healthy controls. BACKGROUND: NDPH is one of the most disabling and least understood primary headache conditions. To date, no studies have considered the role of brain function and structure in pediatric patients with NDPH. METHODS: In this cross-sectional study, resting-state functional and structural images were acquired for 13 patients with NDPH (M age = 15.9, standard deviation [SD] ± 1.4) and 13 age- and sex-matched controls (M age = 16.2, SD ± 1.8) using magnetic resonance imaging. Participants were recruited from the Pediatric Headache Program at Boston Children's Hospital and from the Greater Boston area. In patients, clinical features of NDPH, including disease duration, pain intensity ratings, pain sensitivity, and functional disability were also assessed, and their associations with functional and structural brain alterations were explored. RESULTS: Compared to controls, patients with NDPH demonstrated reduced cortical thickness in the bilateral superior temporal gyrus, left superior, and middle frontal gyrus areas (p < 0.05, Monte Carlo corrected for multiple comparisons). Furthermore, reduced cortical thickness of the left superior frontal gyrus was related to elevated pain sensitivity in NDPH (r = -0.79, p = 0.006). Patients showed altered functional connectivity between regions involved in emotional and cognitive networks of pain, including the amygdala, insula, frontal regions, and cerebellar subregions. CONCLUSION: The present study provides the first preliminary evidence of functional and structural brain differences in pediatric patients with NDPH compared to controls. Identifying alterations in cortical thickness and resting-state connectivity between specific brain regions could provide characteristics of NDPH and probable mechanisms that may guide personalized therapeutic interventions.

Migraine: interactions between brain's trait and state.

It is well established that migraine is a multifactorial disorder. A deep understanding of migraine should be based upon both the underlying traits and the current states affected by different physiological, psychological, and environmental factors. At this point, there is no framework fully meeting these criteria. Here, we describe a broader view of the migraine disorder defined as a dysfunctional brain state and trait interaction. In this model, we consider events that may enhance or diminish migraine responsivity based on an individual's trait and state. This could provide an expanded view for considering how migraine attacks are sometimes precipitated by "triggers" and sometimes not, how these factors only lead to migraine attacks in migraine patients, or how individuals with an increased risk for migraine do not show any symptoms at all. Summarizing recent studies and evidence that support the concept of migraine as a brain state-trait interaction can also contribute to improving patient care by highlighting the importance of precision medicine and applying measures that are able to capture how different traits and states work together to determine migraine.

The Potential Role of Preoperative Pain, Catastrophizing, and Differential Gene Expression on Pain Outcomes after Pediatric Spinal Fusion.

BACKGROUND: Adolescent idiopathic scoliosis is one of the most common spinal deformities in children and adolescents requiring extensive surgical intervention. Due to the nature of surgery, spinal fusion increases their risk of experiencing persistent postsurgical pain. Up to 20% of adolescents report pain for months or years after corrective spinal fusion surgery. AIMS: To examine the influence of preoperative psychosocial factors and mRNA expression profiles on persistent postoperative pain in adolescents undergoing corrective spinal fusion surgery. DESIGN: Prospective, longitudinal cohort study. SETTING: Two freestanding academic children's hospitals. METHODS: Utilizing a longitudinal approach, adolescents were evaluated at baseline (preoperatively) and postoperatively at ±1 month and ±4-6 months. Self-report of pain scores, the Pain Catastrophizing Scale-Child, and whole blood for RNA sequencing analysis were obtained at each time point. RESULTS: Of the adolescents enrolled in the study, 36% experienced persistent pain at final postoperative follow-up. The most significant predictors of persistent pain included preoperative pain severity and helplessness. Gene expression analysis identified HLA-DRB3 as having increased expression in children who experienced persistent pain postoperatively, as opposed to those whose pain resolved. A prospective validation study with a larger sample size is needed to confirm these findings. CONCLUSIONS: While adolescent idiopathic scoliosis is not often classified as a painful condition, providers must be cognizant of pre-existing pain and anxiety that may precipitate a negative recovery trajectory. Policy and practice change are essential for early identification and subsequent intervention.

Changes in Maternal and Paternal Pain-Related Attitudes, Behaviors, and Perceptions across Pediatric Pain Rehabilitation Treatment: A Multilevel Modeling Approach.

Objectives: This prospective study compared paternal versus maternal factors and their impact on child outcomes in the context of an intensive pediatric pain rehabilitation program. Methods: One hundred four youth with treatment refractory chronic pain and their parents enrolled in an intensive pediatric pain rehabilitation program completed measures of pain, functional disability, and parent pain-related attitudes, perceptions, and behaviors at admission and discharge. Results: Linear mixed models were used. Controlling for significant demographic and clinical characteristics, mothers and fathers who were present for the program typically demonstrated significantly better improvement from admission to discharge compared with nonpresent fathers. Mothers made the most significant gains in protective parent responses. Children also had significant decreases in pain and improvements in functioning over time. Conclusions: Results indicate the efficacy of this treatment model for both children with chronic pain and their parents and highlights the importance of parental presence in treatment.

Predicting Postsurgical Satisfaction in Adolescents With Idiopathic Scoliosis: The Role of Presurgical Functioning and Expectations.

BACKGROUND: There is a need to better assess patient satisfaction and surgical outcomes. The purpose of the current study is to identify how preoperative expectations can impact postsurgical satisfaction among youth with adolescent idiopathic scoliosis undergoing spinal fusion surgery. METHODS: The present study includes patients with adolescent idiopathic scoliosis undergoing spinal fusion surgery enrolled in a prospective, multicentered registry examining postsurgical outcomes. The Scoliosis Research Society Questionnaire-Version 30, which assesses pain, self-image, mental health, and satisfaction with management, along with the Spinal Appearance Questionnaire, which measures surgical expectations was administered to 190 patients before surgery and 1 and 2 years postoperatively. Regression analyses with bootstrapping (with n=5000 bootstrap samples) were conducted with 99% bias-corrected confidence intervals to examine the extent to which preoperative expectations for spinal appearance mediated the relationship between presurgical mental health and pain and 2-year postsurgical satisfaction. RESULTS: Results indicate that preoperative mental health, pain, and expectations are predictive of postsurgical satisfaction. CONCLUSIONS: With the shifting health care system, physicians may want to consider patient mental health, pain, and expectations before surgery to optimize satisfaction and ultimately improve clinical care and patient outcomes. LEVEL OF EVIDENCE: Level I-prognostic study.

Changes in sleep habits in adolescents during intensive interdisciplinary pediatric pain rehabilitation.

Sleep behaviors play an important role in the experience of chronic pain in adolescence; less well known is the effect of improved sleep in the context of pain rehabilitation. This study examined changes in sleep habits and their association with pain and functioning following day-hospital interdisciplinary pediatric pain rehabilitation. Participants (84% female) were a cohort of 274 youth (ages 10-18, mean age 14.6 years) with neuropathic or musculoskeletal pain and associated disability who completed measures at admission, discharge, and short term (1-3 month) follow-up. Parents reported on the child's sleep habits; participants reported on pain, functional disability, and school functioning. Results show that sleep habits improved over the course of intensive pain rehabilitation treatment, with continued improvements at follow-up. Sleep habits at discharge correlated with concurrent measures of functional disability and mood symptoms, with healthier sleep habits being associated with less disability and fewer mood symptoms. Furthermore, greater sleep duration, less sleep onset delay, and fewer night wakings correlated with lower pain intensity ratings at discharge. Controlling for change in pain with treatment, baseline sleep habits, age, and concurrent depressive symptoms, sleep habits at discharge predicted global functioning and school functioning measured at follow-up. There was modest support for changes in sleep habits over the course of treatment predicting pain reduction at follow-up, with decreased night wakings significantly predicting reduced pain intensity at follow-up. Improvements in sleep habits may be one mechanism of efficacy for intensive pediatric pain rehabilitation.

Pelvic pain symptoms and endometriosis characteristics in relation to oxidative stress among adolescents and adults with and without surgically-confirmed endometriosis.

Background: While the majority of reproductive-aged females will experience pelvic pain during their lives, biological mechanisms underlying pelvic pain are not well understood. We investigated associations between pelvic pain symptoms and oxidative stress among people with and without surgically-confirmed endometriosis. Methods: Using an enzyme-linked immunosorbent assay, we measured 8-Hydroxy-2'-deoxyguanosine (8-OHdG) in urine samples and corrected for creatinine levels in 434 surgically-confirmed endometriosis participants compared to 605 participants never diagnosed with endometriosis. At enrollment, participants reported details of their pelvic pain symptoms. Linear regression was used to compute geometric mean (GM) creatinine-corrected 8-OHdG levels with 95% confidence intervals (CI) among all participants and those with and without endometriosis separately, adjusting for potential confounders. Interactions by surgically-confirmed endometriosis status were tested by Wald statistics. Results: No trends in 8-OHdG were observed among those with or without endometriosis for severity or frequency of dysmenorrhea, acyclic pelvic pain, dyspareunia or pain with bowel movements. Among endometriosis participants, lower 8-OHdG levels were observed for participants with any white, blue/black, or brown lesions (GM=76.7 versus 82.9 ng/mg; p=0.10), which was primarily driven by lower levels of 8-OHdG for any blue/black lesions (GM=72.8 versus 81.6 ng/mg; p=0.05). Conclusion: While no associations were observed between 8-OHdG and pelvic pain symptoms, future research is needed to assess how other pathways of oxidative damage, e.g. through proteins or lipids, may affect endometriosis-associated symptoms. Additionally, further research is needed to understand differences in oxidative stress among endometriosis lesion sub-phenotypes.

Quantitative somatosensory testing of the abdomen: establishing initial reference values across developmental age and biological sex.

ABSTRACT: Abdominal pain is a common symptom of several debilitating conditions (eg, inflammatory bowel disease, irritable bowel syndrome, and endometriosis) and affects individuals throughout their lifespan. Quantitative sensory testing (QST) reference values exist for many body sites but not the abdomen. Using a QST battery adapted from the German Research Network on Neuropathic Pain, we collected QST data on the upper and lower abdomen in 181 pain-free participants, ages 12 to 50 years, to establish reference values by age and biological sex. The normative values are presented as medians for each QST measure by sex (male, n = 63; female, n = 118) and across 3 age categories (adolescents: 12-19 years, n = 48; young adults: 20-30 years, n = 87; and adults: 31-50 years, n = 46). Evaluating the sensory functioning of the abdomen and characterizing ranges of QST measures is an essential first step in understanding and monitoring the clinical course of sensory abnormalities in patients with underlying diseases affecting the abdomen and pelvis. The impact of age and development on sensory functioning is necessary, given age-related changes in pain perception and modulation.

The long-term impact of cerebellar tumor resection on executive functioning, anxiety, and fear of pain: A mixed methodology pilot study.

This pilot study investigated the long-term impact of a surgery-only treatment (no exposure to other treatments, such as chemotherapy and radiation) for pediatric cerebellar low-grade gliomas on executive function, anxiety, and fear of pain (FOP) beliefs. Twelve patients who underwent surgical glioma resection during childhood (surgery age was 4-16 years, study visit age was 10-28 years), and 12 pain-free controls matched for age, sex, race, and handedness were tested. The spatial extent of resection was precisely mapped using magnetic resonance imaging (MRI). Executive function, anxiety, and FOP were assessed using validated self-report age-appropriate questionnaires for children and adults. Structured clinical interviews at a post-surgery follow-up visit were completed (average: 89 months, range: 20-99). No significant differences in FOP (FOPQ-C t[14 = 1.81, p = 0.09; FOPQ-III t[4] = 0.29, p = 0.79), executive function scores (BRIEF t[20] = 0.30, p = 0.28), or anxiety scores (MASC t[16] = 0.19, p = 0.85; MAQ t[4] = 1.80, p = 0.15) were found in pediatric or adult patients compared to pain-free controls. Clinical interviews mainly categorized pediatric patients as not anxious. One participant reported mild/subclinical anxiety, and one had moderate clinical anxiety. Neither psychologists nor patients endorsed impairments to executive functioning, anxiety, or FOP. Our pilot results suggest that pediatric cerebellar tumor survivors treated with surgery-only have favorable long-term functioning related to these themes. While these results are promising, they will need to be replicated in a larger patient sample.

A preliminary examination of the effects of childhood abuse and resilience on pain and physical functioning in patients with knee osteoarthritis.

OBJECTIVES: We examined associations of a self-reported history of childhood abuse with pain and physical functioning in patients with knee osteoarthritis (KOA) awaiting total knee arthroplasty (TKA). We also explored the potential moderating effects of positive childhood experiences (PCEs), an index of resilience, on these associations. METHODS: Prior to TKA, participants with KOA awaiting surgery (N = 239) completed self-report measures of adverse childhood experiences (ACEs), PCEs, pain, and physical functioning. We evaluated associations of pain and physical functioning (Brief Pain Inventory [BPI] and Western Ontario and McMaster University of Osteoarthritis Index [WOMAC]) based on the experience of ACEs (childhood abuse), with PCEs (childhood happiness and supportive parental care) as potential moderators. RESULTS: Greater exposure to childhood abuse was positively correlated with BPI pain interference as well as WOMAC pain and functioning scores. Additionally, childhood happiness and supportive parental care moderated the positive associations of childhood abuse with pain and physical functioning; though, surprisingly, the adverse effects of childhood abuse on these outcomes were more pronounced among participants with high levels of childhood happiness and supportive parental care. CONCLUSION: Overall, results show an association between a self-reported history of childhood abuse and pain and functioning in patients with KOA awaiting TKA. However, PCEs did not protect against the negative consequences of childhood abuse in our cohort. Further research is needed to validate these associations and gain a more comprehensive understanding of the complex interplay between childhood abuse and PCEs and their potential influences on pain experiences in adults with chronic pain conditions, including KOA.

Subgroups of pelvic pain are differentially associated with endometriosis and inflammatory comorbidities: a latent class analysis.

ABSTRACT: Chronic pelvic pain is heterogeneous with potentially clinically informative subgroups. We aimed to identify subgroups of pelvic pain based on symptom patterns and investigate their associations with inflammatory and chronic pain-related comorbidities. Latent class analysis (LCA) identified subgroups of participants (n = 1255) from the Adolescence to Adulthood (A2A) cohort. Six participant characteristics were included in the LCA: severity, frequency, and impact on daily activities of both menstruation-associated (cyclic) and non-menstruation-associated (acyclic) pelvic pain. Three-step LCA quantified associations between LC subgroups, demographic and clinical variables, and 18 comorbidities (10 with prevalence ≥10%). Five subgroups were identified: none or minimal (23%), moderate cyclic only (28%), severe cyclic only (20%), moderate or severe acyclic plus moderate cyclic (9%), and severe acyclic plus severe cyclic (21%). Endometriosis prevalence within these 5 LCA-pelvic pain-defined subgroups ranged in size from 4% in "none or minimal pelvic pain" to 24%, 72%, 70%, and 94%, respectively, in the 4 pain subgroups, with statistically significant odds of membership only for the latter 3 subgroups. Migraines were associated with significant odds of membership in all 4 pelvic pain subgroups relative to those with no pelvic pain (adjusted odds ratios = 2.92-7.78), whereas back, joint, or leg pain each had significantly greater odds of membership in the latter 3 subgroups. Asthma or allergies had three times the odds of membership in the most severe pain group. Subgroups with elevated levels of cyclic or acyclic pain are associated with greater frequency of chronic overlapping pain conditions, suggesting an important role for central inflammatory and immunological mechanisms.

What does it take? Comparing intensive rehabilitation to outpatient treatment for children with significant pain-related disability.

OBJECTIVES: This study compared outcomes between day hospital pain rehabilitation patients and patients engaged in outpatient multidisciplinary pain treatment. METHODS: This study included 100 children who presented for an initial tertiary care pain clinic evaluation. 50 patients enrolled in intensive day hospital pain rehabilitation and 50 patients pursued outpatient multidisciplinary treatment. Across 2 time points, children completed measures of functional disability, pain-related fear, and readiness to change and parents completed measures of pain-related fear and readiness to change. RESULTS: Across both treatment modalities, patients and parents reported improvements. Patients enrolled in intensive pain rehabilitation had significantly larger improvements in functional disability, pain-related fear, and readiness to change. Parents of day hospital patients reported larger declines in child pain-related fear and increased readiness to change compared with their outpatient counterparts. Discussion For patients with high levels of pain-related disability and distress, intensive pain rehabilitation provides rapid, dramatic improvements in functioning.

Exploring Comorbidities in Adolescent and Young Adults with Hypermobile Ehlers-Danlos Syndrome with and without a Surgical History: A Preliminary Investigation.

Ehlers-Danlos Syndrome (EDS) is a rare disease affecting the skin, joints, vasculature, and internal organs. Approximately 85% of those affected are categorized as the hypermobile type (hEDS), which is associated with numerous medical and psychiatric comorbidities, including chronic pain. Additionally, approximately 71% of patients with hEDS undergo at least one surgical procedure; however, indicators for surgery and pain outcomes after surgery are poorly understood. This preliminary study used a medical chart review to identify the frequency and nature of comorbidities in a cohort of adolescents and young adult patients with hEDS and a surgical history compared to those without a surgical history. Results showed that patients diagnosed with hEDS who underwent surgery reported significantly more comorbidities (e.g., CRPS, IBS, Fibromyalgia, POTS, hypothyroidism, etc.) than those who did not have surgery. Seventy percent of individuals who presented for surgery fell within the categories of orthopedic, gastrointestinal, or laparoscopic/endometriosis-related surgeries. Identifying patients with hEDS who are at risk for needing surgery will help identify the mechanisms contributing to risk factors for poor surgical outcomes. The results of this study may be instructive in the management and care of hEDS patients undergoing surgery.

Can pain under anesthesia be measured? Pain-related brain function using functional near-infrared spectroscopy during knee surgery.

Significance: Quantitative measurement of perisurgical brain function may provide insights into the processes contributing to acute and chronic postsurgical pain. Aim: We evaluate the hemodynamic changes in the prefrontal cortex (medial frontopolar cortex/mFPC and lateral prefrontal cortex) and the primary somatosensory cortex/S1 using functional near-infrared spectroscopy (fNIRS) in 18 patients (18.2±3.3 years, 11 females) undergoing knee arthroscopy. Approach: We examined the (a) hemodynamic response to surgery and (b) the relationship between surgery-modulated cortical connectivity (using beta-series correlation) and acute postoperative pain levels using Pearson's r correlation with 10,000 permutations. Results: We show a functional dissociation between mFPC and S1 in response to surgery, where mFPC deactivates, and S1 activates following a procedure. Furthermore, the connectivity between (a) left mFPC and right S1 (original r=-0.683, ppermutation=0.001), (b) right mFPC and right S1 (original r=-0.633, ppermutation=0.002), and (c) left mFPC and right S1 (original r=-0.695, ppermutation=0.0002) during surgery were negatively associated with acute postoperative pain levels. Conclusions: Our findings suggest that greater functional dissociation between mFPC and S1 is likely the result of inadequately controlled nociceptive barrage during surgery leading to more significant postoperative pain. It also supports the utility of fNIRS during the perioperative state for pain monitoring and patient risk assessment for chronic pain.

Quantitative sensory testing in a magnetic resonance environment: considerations for thermal sensitivity and patient safety.

Introduction: Quantitative sensory testing (QST) is often used to understand the perceptual basis of acute and chronic conditions, including pain. As the need grows for developing a mechanistic understanding of neurological pathways underlying perception in the basic and clinical sciences, there is a greater need to adapt techniques such as QST to the magnetic resonance (MR) environment. No studies have yet evaluated the impact of the MR environment on the perception of thermal stimuli. This study aimed to evaluate the differences in temperature sensitivity outside an MR environment and during an MRI scanning session. We hypothesized that there would be a difference in how participants reported their pain sensitivity between the two environments. Methods: Healthy participants underwent thermal QST outside the MR scanning environment, where they were asked to rate the temperature of a noxious stimulus at which they perceived their pain to be 7/10, using a Likert scale ranging from 0 to 10. Participants repeated this procedure inside a 3.0 T MRI approximately 30 min later. We repeated our investigation in a clinical cohort of participants with a chronic pain condition. Results: There were statistically significant changes of 1.1°C in thermal sensitivity between environments. This increase in pain threshold was found in healthy participants and replicated in the clinical cohort. Discussion: Findings can be applied toward improving MR safety, the resolution of brain pathways underlying pain mechanisms, and to more broadly comment on the impact of the MR environment on investigations that integrate perception-influenced processes.