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The objective of this study was to determine physician perceptions regarding the importance of and comfort with the use of medical genetics and genomics in medical education and practice, as well as physician expectations for medical trainees.A retrospective survey was sent to physicians employed by a health system associated with a public medical school to assess their perceived training in medical genetics and genomics and their comfort level with ordering genetic testing.Despite reporting formal genetics training in medical schools, clinicians' comfort with and knowledge in this content area does not meet personal expectations of competency. Though physicians report some discomfort with the use of medical genetics and genomics, the majority also believe that its impact on practice will increase in the next five years. Survey recipients were also asked about their expectations for preparation in the same domains for medical students and incoming residents. The surveyed physicians expect a high level of competency for medical students and incoming residents.Our study revealed that practicing physicians feel current medical curricula do not produce physicians with the necessary competency in medical genetics and genomics. This is despite physicians' perceived importance of this domain in medical practice. Our findings suggest a need for re-evaluation of medical genetics and genomics education at all levels of training.

Identifying the genetic determinants of pain is a scientific imperative given the magnitude of the global health burden that pain causes. Here, we report a genetic screen for nociception, performed under the auspices of the International Mouse Phenotyping Consortium. A biased set of 110 single-gene knockout mouse strains was screened for 1 or more nociception and hypersensitivity assays, including chemical nociception (formalin) and mechanical and thermal nociception (von Frey filaments and Hargreaves tests, respectively), with or without an inflammatory agent (complete Freund's adjuvant). We identified 13 single-gene knockout strains with altered nocifensive behavior in 1 or more assays. All these novel mouse models are openly available to the scientific community to study gene function. Two of the 13 genes (Gria1 and Htr3a) have been previously reported with nociception-related phenotypes in genetically engineered mouse strains and represent useful benchmarking standards. One of the 13 genes (Cnrip1) is known from human studies to play a role in pain modulation and the knockout mouse reported herein can be used to explore this function further. The remaining 10 genes (Abhd13, Alg6, BC048562, Cgnl1, Cp, Mmp16, Oxa1l, Tecpr2, Trim14, and Trim2) reveal novel pathways involved in nociception and may provide new knowledge to better understand genetic mechanisms of inflammatory pain and to serve as models for therapeutic target validation and drug development.

Background Persistently high chronic stress can lead to maladaptive psychological, behavioral, and physiological stress responses and poor mental and physical health, highlighting the importance of identifying individuals at increased risk. Chronic health condition diagnosis and genetics are 2 characteristics that can influence stress, stress response, and health outcomes. Purpose Food allergy (FA) and celiac disease (CD) require constant vigilance in daily life and can lead to increased stress. The purpose of this exploratory analysis was to examine the association of variants in selected stress-related genes with stress exposures, stress, clinical measures of physiological stress response, and mental health symptoms in adults with and without FA or CD. Methods We compared stress exposures, symptoms of PTSD, depression, anxiety, and stress, BMI, and waist-hip ratio between cases and controls. We analyzed the association of SNPs in genes with known or hypothesized associations with stress-related measures in 124 cases and 124 matched controls: CRHBP (rs7718461, rs10474485), CRHR1 (rs242940) and OXTR (rs2268490). For this exploratory study, p-values ≤ 0.10 were considered suggestive. Results For cases and controls, rs7718461 was associated with stress symptoms, rs2268490 with symptoms of stress and PTSD, and rs242940 with symptoms of stress, PTSD, anxiety, and depression. Further analyses found that stress-related outcomes in individuals with FA or CD may be influenced by SNP genotype. Conclusions Given these suggestive findings, larger prospective studies should examine similar relationships in individuals with other chronic health conditions, incorporating factors such as environmental exposures, individual experiences, and epigenetic modifications.

Background:Nonpharmacologic stress reduction interventions provide an opportunity to modify chronic pain trajectories; however, the biological mechanisms underlying these interventions are poorly understood.Objectives:To examine clinical literature published in 2012–2018 with the goals of (1) identifying which biological mechanisms or biomarkers are currently being measured in nonpharmacologic stress reduction intervention studies for individuals with chronic pain and (2) evaluating the evidence to determine whether these stress reduction interventions lead to changes in (a) pain outcomes and/or (b) measured biomarkers.Data sources:Scientific articles in the electronic databases PubMed/Medline, Cumulative Index of Nursing and Allied Health Literature, PsychINFO, and SCOPUS following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.Study selection:Randomized controlled trials and quasi-experimental studies that recruited subjects with a chronic pain condition, examined a relationship between a nonpharmacologic stress reduction intervention and pain-related outcome(s), and included measurement of a biomarker.Results:The 13 articles that met inclusion criteria spanned four nonpharmacologic stress reduction categories: mindfulness-based stress reduction, physical exercise, manual therapies, and biofeedback. Methods for studying biomarkers included measuring biological samples, neurological function, and autonomic control. Although all studies investigated both biological measures and pain outcomes, only three demonstrated an association between the biomarker(s) and pain-related outcomes.Conclusions:The results of this review highlight the complex nature of stress–pain relationships and the lack of rigorous clinical research identifying specific stress-related biological factors that modulate pain outcomes. Stress reduction interventions remain a favorable method for symptom management in patients living with chronic pain, but consistency in study measures and design is needed for robust evaluation.

Objectives A number of factors, including heritability and the environment, contribute to risk of transition from acute low back pain to chronic low back pain (CLBP). The aim of this study was to (1) compare somatosensory function and pain ratings at low back pain (LBP) onset between the acute low back pain and CLBP conditions and (2) evaluate associations between BDNF and COMT polymorphisms and expression levels at LBP onset to acute and chronic pain burden and risk for transition to the chronic pain state. Methods In this longitudinal study, 220 participants were enrolled following recent onset of LBP and data were collected until the LBP resolved or until the end of the study at 6 months. Forty-two participants' pain resolved before 6 weeks from onset and 42 participants continued to have pain at 6 months. Patient-reported pain burden, somatosensory function (quantitative sensory testing), and blood samples were collected at each study visit. Results CLBP is associated with greater pain burden and somatosensory hypersensitivity at the time of LBP onset. COMT rs4680 genotype (GG) was associated with acute cold pain sensitivity and with the risk for transition to CLBP while COMT expression was independently associated with risk for transition. Discussion CLBP was characterized by higher reported pain burden and augmented hypersensitivity at LBP onset. COMT expression and genotype were associated with acute pain burden and likelihood of transition to CLBP.

Thermal nociception involves the transmission of temperature-related noxious information from the periphery to the CNS and is a heritable trait that could predict transition to persistent pain. Rodent forward genetics complement human studies by controlling genetic complexity and environmental factors, analysis of end point tissue, and validation of variants on appropriate genetic backgrounds. Reduced complexity crosses between nearly identical inbred substrains with robust trait differences can greatly facilitate unbiased discovery of novel genes and variants. We found BALB/cByJ mice showed enhanced sensitivity on the 53.5°C hot plate and mechanical stimulation in the von Frey test compared to BALB/cJ mice and replicated decreased gross brain weight in BALB/cByJ versus BALB/cJ. We then identified a quantitative trait locus (QTL) on chromosome 13 for hot plate sensitivity (LOD = 10.7; p < 0.001; peak = 56 Mb) and a QTL for brain weight on chromosome 5 (LOD = 8.7; p < 0.001). Expression QTL mapping of brain tissues identified H2afy (56.07 Mb) as the top transcript with the strongest association at the hot plate locus (FDR = 0.0002) and spliceome analysis identified differential exon usage within H2afy associated with the same locus. Whole brain proteomics further supported decreased H2AFY expression could underlie enhanced hot plate sensitivity, and identified ACADS as a candidate for reduced brain weight. To summarize, a BALB/c reduced complexity cross combined with multiple-omics approaches facilitated identification of candidate genes underlying thermal nociception and brain weight. These substrains provide a powerful, reciprocal platform for future validation of candidate variants.

Background Despite the emphasis on exercise to reduce pain and improve function among people with chronic low back pain (cLBP), little is known about the underlying mechanism of the impact of exercise on the neurophysiological and gene transcription alterations that characterize cLBP. Objectives To present a study protocol to examine the feasibility, acceptability, and initial efficacy of Problem-Solving Pain to Enhance Living Well (PROPEL) with the support of nurse consultations and wearable activity-tracking technology on self-management (SM) knowledge, skills, physical activity, and pain and to examine the differential neurophysiological and gene expression profiles in cLBP participants from pre- to post-PROPEL. Methods A pretest and posttest study is employed on 40 adults ages 18-60 years with cLBP who do not have serious complications and/or comorbidities that affect sensorimotor function. Participants will receive video modules focused on SM and biweekly phone consultations to facilitate symptom monitoring and problem-solving while increasing physical activity frequency and duration. Participants will be assessed for outcomes including SM skills, physical activity, and pain every 2 weeks for 12 weeks. We will examine the participants' differential neurophysiological and gene expression profiles at 12 weeks postintervention and correlate these outcomes with the total duration of physical activity. Results The study began in September 2018. Of the 99 subjects that were screened, 23 were enrolled and 8 completed data collection. Discussion Comparing the neurophysiological and gene expression profiles of people with cLBP exposed to PROPEL could inform the development of interventions that offer personalized physical activity dosage along with general SM support. Web-based programs such as PROPEL have the potential to enhance accessibility of evidence-based interventions that improve functionality and quality of life among people living with cLBP.

Spinal cord injury (SCI) is a complex syndrome that has profound effects on patient well-being, including the development of medically-resistant chronic pain. The mechanisms underlying SCI pain have been the subject of thorough investigation but remain poorly understood. While the majority of the research has focused on changes occurring within and surrounding the site of injury in the spinal cord, there is now a consensus that alterations within the peripheral nervous system, namely sensitization of nociceptors, contribute to the development and maintenance of chronic SCI pain. Here we demonstrate that thoracic spinal contusion injury results in the emergence of autotomy and spasticity, both indicators of spontaneous pain, in areas below the level of the injury within 24 hr of SCI. These behaviors were associated with hindpaw edema and elevated cutaneous calcitonin gene-related peptide (CGRP) concentration. Electrophysiological recordings using an ex vivo skin/nerve/DRG/spinal cord preparation demonstrated that SCI increased mechanical and thermal sensitivity, as well as the incidence of spontaneous activity (SA) and afterdischarge (AD), in below-level C-fiber nociceptors 24 hr following injury. Interestingly, the distribution of nociceptors that exhibit SA and AD are not identical, and the development of SA was observed more frequently in nociceptors with low thermal thresholds, while AD was found more frequently in nociceptors with high thermal thresholds. These results demonstrate that SCI causes the rapid-onset of peripheral inflammation-like processes that sensitize nociceptors, which may contribute to the early emergence and persistence of chronic SCI pain.

Background There is often dissociation between inflammatory activity and abdominal pain in children with inflammatory bowel disease (IBD), suggesting other factors may play a role in the pain experience. Methods Patients (8 to 17 years) newly diagnosed with IBD were enrolled in the ALLAY Study: Assessing Risk Factors for Abdominal Pain in Children with Inflammatory Bowel Disease (NCT02984059). At diagnostic colonoscopy, 3 rectal biopsies were collected, and gene expression analysis was performed using Qiagen RT2 Profiler Neuropathic and Inflammatory Pain PCR Array. Relative fold difference in gene expression for 84 pain-associated genes was calculated using the 2-ΔΔ Cq method compared with pain-free controls. Factors affecting pain burden (Pain Burden Interview; PBI) were analyzed, including age, sex, rectal inflammation, and gene expression. Data were analyzed using multiple stepwise linear regression and 2-tailed t tests (P ≤ 0.05). Results Thirty-nine newly diagnosed IBD patients were included (65% male, mean age 12.75 years [SD 2.63], 23 Crohn’s disease, 16 ulcerative colitis), along with 3 controls. Mean PBI score was 7.73 (SD 6.4, range 0 to 23) for all patients. Age and sex were not predictive of pain burden, but disease activity score was (P = 0.03). Expression of TRPV3, OPRM1, P2X3, SCN9A, PTGS2, and MAPK14 were associated with PBI score. Subsequent 2-tailed t tests comparing patients with no pain (PBI score ≦ 2, N = 11) to those with pain (PBI > 2, N = 28) confirmed differential expression of TRPV3, PTGS2, and MAPK14 was in patients with pain (all P < 0.05). Conclusion Pain burden in newly diagnosed IBD patients may be linked to TRPV3, PTGS2, and MAPK14 expression, suggesting potential therapeutic targets for managing pain in IBD.

BACKGROUND In children with functional dyspepsia (FD), genes involved in pain modulation may be differentially expressed contributing to chronic pain. METHODS Children with suspected FD (cases) and known eosinophilic esophagitis (controls) undergoing esophagogastroduodenoscopy completed the Rome IV Diagnostic, Pain Burden and Frequency Severity-Duration questionnaires. Two antral and two duodenal biopsies were collected and relative fold differences in gene expression for 84 pain-associated genes compared to pain-free controls were calculated. RESULTS Sixty-six subjects with FD (postprandial distress syndrome = 34, epigastric pain syndrome = 7, both = 25; 65% female; mean age 13.7 years) and 13 pain-free controls (8% female; mean age 12.7) were studied. There were no significant differences in antral and duodenal eosinophilic counts or distribution between the pain and pain-free groups. Pain severity and burden did not differ significantly between FD subgroups and neither measure significantly correlated with eosinophil counts in the antrum or duodenum. Analysis of 47 antral and 39 duodenal biospecimens revealed 5 candidate genes significantly associated with pain burden: antral EDN1, PTGES3 and duodenal HTR1A, P2Y1, SCN3A (p

PurposeTo evaluate associations among breast and nipple pain sensitivity and candidate pain sensitivity single-nucleotide polymorphisms [SNPs], (COMT rs6269, rs4633, rs4818, rs4680 and OXTR rs2254298, rs53576) in breastfeeding women.DesignA secondary analysis of sixty women participating in a pilot randomized controlled trial of a pain self-management intervention.MethodsAll participants underwent standardized mechanical somatosensory testing for an assessment of pain sensitivity and provided baseline buccal swabs for genetic analysis. At 1, 2, and 6 weeks postpartum, women self-reported breast and nipple pain severity using a visual analogue scale.ResultsWomen with the minor allele OXTR rs53576 reported 8.18-fold higher breast and nipple pain severity over time. For every 1-unit increase in mechanical detection threshold and windup ratio, women reported 16.51-fold and 4.82-fold higher breast and nipple pain severity respectively. Six women with the OXTR rs2254298 minor allele reported allodynia.DiscussionThe presence of OXTR alleles in women with enhanced pain sensitivity suggests a phenotype of genetic risk for ongoing breast and nipple with potential for pain-associated breastfeeding cessation. Somatosensory testing identified women who reported higher breast and nipple pain during the first weeks of breastfeeding.Clinical ImplicationsPain sensitivity testing can help to identify women at risk of intolerable and/or ongoing breastfeeding pain who may benefit from additional support to mitigate early breastfeeding cessation. Targeted interventions are needed to address breastfeeding pain, including management of infant latch, positioning, and infection as well as support for self-management of breastfeeding pain.

BACKGROUND: Thirty percent of women who seek professional breastfeeding support require assistance with ongoing breast and nipple pain and < 50% of women report resolution of their pain. It is unknown if there is a molecular risk for ongoing breast and nipple pain during breastfeeding. AIM –: To evaluate associations among breast and nipple pain sensitivity and candidate pain sensitivity single-nucleotide polymorphisms [SNPs], (COMT rs6269, rs4633, rs4818, rs4680 and OXTR rs2254298, rs53576) in breastfeeding women. DESIGN -: A secondary analysis of a pilot randomized controlled trial of a pain self-management intervention conducted over 6 weeks postpartum. Setting and Participants - Sixty women were recruited from two hospital settings after birth. METHODS –: All participants underwent standardized mechanical somatosensory testing for an assessment of pain sensitivity and provided baseline buccal swabs for genetic analysis. At 1, 2, and 6 weeks postpartum, women self-reported breast and nipple pain severity using a visual analogue scale. RESULTS -: Women with the minor allele OXTR rs53576 reported 8.18-fold higher breast and nipple pain severity over time. For every 1-unit increase in Mechanical detection threshold and windup ratio, women reported 16.51-fold and 4.82-fold higher breast and nipple pain severity respectively. Six women with the OXTR rs2254298 minor allele reported allodynia. CONCLUSION -: The presence of OXTR alleles in women with enhanced pain sensitivity suggests a phenotype of genetic risk for ongoing breast and nipple with potential for pain-associated breastfeeding cessation. Somatosensory testing identified women who reported higher breast and nipple pain during the first weeks of breastfeeding.

Aim To investigate the degree to which psychological stress, self-reported pain scores, and pain sensitivity during an acute state of low back pain (LBP) predict the development of persistent LBP trajectories. Background Identifying which factors influence LBP trajectories is critical to understand why some individuals experience persistent LBP and to illuminate areas for nursing intervention. Methods A secondary data analysis of a prospective study examining trajectories of LBP was conducted. The sample was comprised of 217 adults with acute-onset LBP recruited from the community and followed over 24 weeks. Variables of interest included demographic data, perceived stress scores, self-reported pain scores, and somatosensory characteristics collected within the first 4 weeks of LBP onset. The data were analyzed using non-parametric bivariate comparisons and a semi-parametric Cox proportional hazards model with interval-censoring. Results Individuals with higher psychological stress scores were less likely to experience pain resolution (Hazard ratio [HR] = 0.555, 95% confidence interval [CI] = 0.36–0.85, p = 0.02). After adjustment for covariates in the final model, the analysis revealed household income (HR = 2.79, 95% CI [1.63–4.67], p Conclusion Heightened psychological stress and pain severity as well as decreased pressure pain thresholds were indicated as influential factors of LBP trajectories. Household income was identified as the dominant predictor, demonstrating that individuals with a higher household income were more likely to resolve their pain. Strategies which integrate assessment of stress, self-reported pain scores, pain sensitivity, and social determinants for patients experiencing pain are needed to advance nursing care.

Background Childhood cancer survivorship can be described as a lifelong experience that requires vigilant follow-up care and continual support. Although there is growing qualitative and quantitative literature on this experience, articles focusing on qualitative synthesis are lacking. Qualitative metasynthesis can further facilitate the knowledge of survivorship experiences to inform care. Objective The aim of this qualitative metasynthesis was to investigate the experiences of childhood cancer survivors and develop an integrated understanding of the survivorship experience. Methods The method of qualitative meta-ethnography guided this research. Data extracted from the studies were directly compared through reciprocal translation. Results A total of 18 qualitative articles met the inclusion criteria. The authors identified 4 key metaphors, including Transcendence, Lingering Shadows, Fortifying Bonds, and Ongoing Acclimation. The metaphors are brought together by 3 essential concepts that drive the survivorship experience: (1) recognition of wisdom gained, (2) acknowledgment of vulnerabilities, and (3) actions taken to manage present and future. Together, these metaphors and essential concepts make up the global theme "Forced Enlightenment." Conclusion This metasynthesis illuminates the complex nature of the childhood cancer survivorship experience, in which survivors work to grow beyond their treatment experience while inevitably being tied to it. Next steps should include further exploration of individual metaphors and validation of forced enlightenment as an experience. Implications for practice Each of the metaphors may be used to guide the development of nursing interventions. Translation to clinical practice should focus on prioritizing coping and adaptation skills during cancer treatment, which can be carried through survivorship.

Irritable bowel syndrome (IBS) is a functional gut disorder that typically manifests in early adult years. IBS patients report that pain is the most distressing symptom with the greatest impact on quality of life. Pain-sensitivity genes and the gut microbiome may influence severity of symptoms as well as response to self-management (SM) interventions. Based on current understanding of the science of SM, pain neurophysiology, and the gut-brain axis, our team developed a pain SM intervention to be added to evidence-based self-management instruction to increase the individual's SM knowledge and skills (self-efficacy, self-regulation, and goal-setting). The purpose of this randomized controlled longitudinal pilot study is to examine the feasibility, acceptability, and preliminary effectiveness of the IBS-pain SM intervention on IBS-pain SM behaviors and related health outcomes. A sample of 80 young adults (age 18–29 years old) will be recruited and randomly assigned to the experimental or control group. Both groups will receive 10 electronic video modules focused on IBS-pain SM knowledge and skills. The experimental group also will receive nurse-led one-on-one phone consultations to facilitate monitoring and problem-solving. All participants will be followed over 12 weeks. Primary outcomes will be measured at baseline, 6 weeks, and 12 weeks, including IBS-pain SM behaviors, quality of life, and well-being. The influence of pain-sensitivity genes and the gut microbiome on IBS-pain SM behaviors and health outcomes also will be assessed.

Problem Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity among children and adolescents and the most frequent reason for corrective spinal fusion (SF). Of the children and adolescents who undergo SF, a significant number will experience persistent postoperative pain (PPP). This integrative literature review was conducted to identify and synthesize perioperative factors that may contribute to risk of developing PPP. Eligibility Criteria Articles which addressed PPP within the last 10 years and primary research on postoperative pain outcomes in adolescents after SF were selected for review. Sample 15 articles which met eligibility criteria were included. Results Preoperative pain intensity was the most significant factor identified in the development of PPP and increased postoperative pain. Social function and psychological factors also have role in the development of PPP. There were no theoretical models or frameworks for evaluating PPP incidence in adolescent with AIS after SF. Conclusions Perioperative factors such as, preoperative pain, correction magnitude, pain coping, anxiety and social functioning are vital to understanding a child's risk of PPP following SF. There is a need for theoretically-based studies to assess PPP among children and adolescents with AIS after SF surgery. Implications The Biobehavioral Pain Network (BPN) model was proposed, to encompass biological, social and psychological domains which may be responsible for incidence of PPP in children undergoing SF. Such a model can be used to systematically develop and evaluate personalized postoperative pain management strategies for this patient population.

Breast milk stem cells are hypothesized to be involved in infant health and development. Our research team is the first known team to enroll mothers of hospitalized preterm infants during the first few weeks of lactation and compare stem cell phenotypes and gene expression to mothers of healthy full-term infants.Participants were recruited from a Level IV Neonatal Intensive Care Unit (preterm dyads) and the community (full-term dyads) in the northeastern United States.Mothers of hospitalized preterm infants (37 weeks gestational age at birth) and mothers of healthy full-term infants (39 weeks gestational age at birth).Breast milk stem-like cell populations were identified in both preterm and full-term breast milk samples. The data suggest variability in the proportion of stem cell phenotypes present, as well as statistically significant differential expression (both over- and underexpression) of stem cell-specific genetic markers when comparing mothers' milk for preterm and full-term births.Our findings indicate that (1) stem cells are present in preterm breast milk; (2) differential expression of stem cell-specific markers can be detected in preterm and full-term breast milk samples; and (3) the percentage of cells expressing the various stem cell-specific markers differs when preterm and full-term breast milk samples are compared.

Infants who begin early life in the medicalized environment of the neonatal intensive care unit (NICU) experience disruption to numerous fundamental expectancies. In the NICU, infants are exposed to chronic, extreme stressors that include painful medical procedures and parental separation. Due to their preverbal stage of development, infants are unable to fully express these experiences, and linking these experiences to long-term outcomes has been difficult. This clinical article proposes the terminology Infant Medical Trauma in the NICU (IMTN) to describe the infant experience. Following a discussion of the NICU as an adverse childhood event, the article has three sections: (a) the unique and critical factors that define the newborn period, (b) a review of the IMTN conceptual model, and (c) recommendations for supportive neuroprotective strategies to moderate the intensity of adverse NICU infant experiences.

Women with breast cancer frequently report distressing symptoms during and after treatment that can significantly erode quality of life (QOL). Symptom burden among women with breast cancer is of complex etiology and is likely influenced by disease, treatment, and environmental factors as well as individual genetic differences. The purpose of the present study was to examine the relationships between genetic polymorphisms within Neurotrophic tyrosine kinase receptor 1 (NTRK1), Neurotrophic tyrosine kinase receptor 2 (NTRK2), and catechol-O-methyltransferase ( COMT) and patient symptom burden of QOL, pain, fatigue, anxiety, depression, and sleep disturbance before, during, and after treatment for breast cancer in a subset of participants ( N = 51) in a randomized clinical trial of a novel symptom-management modality for women with breast cancer undergoing chemotherapy. Patients were recruited at the time of initial breast cancer diagnosis and completed all survey measures at the time of recruitment, after the initiation of treatment (surgery and/or chemotherapy), and then following treatment conclusion. Multiple linear regression analyses revealed significant associations between NTRK2 and COMT single nucleotide polymorphism (SNP) genotype and symptom burden. Two COMT variants were associated with the specific symptoms of anxiety and QOL measures prior to the initiation of chemotherapy as well as pain interference and severity during and after treatment. Genotype at the NTRK2 SNP rs1212171 was associated with both sleep disturbance and fatigue. These findings, while exploratory, indicate that the genotypes of NTRK2 and COMT may contribute to relative risk for symptom burden during and shortly after the period of chemotherapy in women with early stage breast cancer.

Sensory neurons are chemically and functionally heterogeneous, and this heterogeneity has been examined extensively over the last several decades. These studies have employed a variety of different methodologies, including anatomical, electrophysiological, and molecular approaches. Recent studies using next-generation sequencing techniques have examined the transcriptome of single sensory neurons. Although these reports have provided a wealth of exciting new information on the heterogeneity of sensory neurons, correlation with functional types is lacking. Here, we employed retrograde tracing of cutaneous and muscle afferents to examine the variety of mRNA expression profiles of individual, target-specific sensory neurons. In addition, we used an ex vivo skin/nerve/dorsal root ganglion/spinal cord preparation to record and characterize the functional response properties of individual cutaneous sensory neurons that were then intracellularly labeled with fluorescent dyes, recovered from dissociated cultures, and analyzed for gene expression. We found that by using single-cell quantitative polymerase chain reaction techniques and a set of 28 genes, we can identify transcriptionally distinct groups. We have also used calcium imaging and single-cell quantitative polymerase chain reaction to determine the correlation between levels of mRNA expression and functional protein expression and how functional properties correlated with the different transcriptional groups. These studies show that although transcriptomics does map to functional types, within any one functional subgroup, there are highly variable patterns of gene expression. Thus, studies that rely on the expression pattern of one or a few genes as a stand in for physiological experiments, runs a high risk of data misinterpretation with respect to function.

Identification of genetic variants that influence susceptibility to pain is key to identifying molecular mechanisms and targets for effective and safe therapeutic alternatives to opioids. To identify genes and variants associated with persistent pain, we measured late-phase response to formalin injection in 275 male and female Diversity Outbred mice genotyped for over 70,000 single nucleotide polymorphisms. One quantitative trait locus reached genome-wide significance on chromosome 1 with a support interval of 3.1 Mb. This locus, Nociq4 (nociceptive sensitivity quantitative trait locus 4; MGI: 5661503), harbors the well-known pain gene Trpa1 (transient receptor potential cation channel, subfamily A, member 1). Trpa1 is a cation channel known to play an important role in acute and chronic pain in both humans and mice. Analysis of Diversity Outbred founder strain allele effects revealed a significant effect of the CAST/EiJ allele at Trpa1, with CAST/EiJ carrier mice showing an early, but not late, response to formalin relative to carriers of the 7 other inbred founder alleles (A/J, C57BL/6J, 129S1/SvImJ, NOD/ShiLtJ, NZO/HlLtJ, PWK/PhJ, and WSB/EiJ). We characterized possible functional consequences of sequence variants in Trpa1 by assessing channel conductance, TRPA1-TRPV1 interactions, and isoform expression. The phenotypic differences observed in CAST/EiJ relative to C57BL/6J carriers were best explained by Trpa1 isoform expression differences, implicating a splice junction variant as the causal functional variant. This study demonstrates the utility of advanced, high-precision genetic mapping populations in resolving specific molecular mechanisms of variation in pain sensitivity.

The majority of women experience pain during breastfeeding initiation with few strategies to manage breast and nipple pain. In fact, women cite breast and nipple pain as among the most common reasons for breastfeeding cessation. In order to address this important issue, we developed a Breastfeeding Self-Management (BSM) intervention, based on the Individual and Family Self-Management Theory Framework. In this framework, self-management is conceptualized as a process in which women use knowledge, beliefs, and social facilitation to achieve breastfeeding goals. The purpose of this longitudinal pilot randomized controlled trial was to test the feasibility, acceptability, and preliminary efficacy of the BSM intervention with women initiating breastfeeding. Recruitment of 60 women intending to breastfeed occurred within 48 hours of delivery, and women were randomized to either the intervention or usual care group. The BSM intervention group received breastfeeding SM education modules that included information of how to manage breast and nipple pain and self-management support through bi-weekly texting from the study nurse, and were asked to complete a daily breastfeeding journal. Primary outcomes measured at baseline, 1, 2, and 6 weeks will be used to 1) evaluate feasibility, acceptability, and preliminary efficacy of the BSM intervention, and 2) assess the influence of protective and risk factors of breastfeeding pain (including individual genetic polymorphisms related to pain sensitivity) on process variables for self-management of breastfeeding and breastfeeding pain, and on proximal (breastfeeding pain severity and interference, breastfeeding frequency) and distal outcomes (breastfeeding exclusivity and duration and general well-being).

Sensory neurons are chemically and functionally heterogeneous and this heterogeneity has been examined extensively over the last several decades. These studies have employed a variety of different methodologies, including anatomical, electrophysiological and molecular approaches. Recent studies using next generation sequencing techniques have examined the transcriptome of single sensory neurons. Although, these reports have provided a wealth of exciting new information on the heterogeneity of sensory neurons, correlation with functional types is lacking. Here, we employed retrograde tracing of cutaneous and muscle afferents to examine the variety of mRNA expression profiles of individual, target-specific sensory neurons. In addition, we used an ex vivo skin/nerve/DRG/ spinal cord preparation to record and characterize the functional response properties of individual cutaneous sensory neurons that were then intracellularly labeled with fluorescent dyes, recovered from dissociated cultures and analyzed for gene expression. We found that by using single cell qPCR techniques and a limited set of genes, we can identify transcriptionally distinct groups. We have also used calcium imaging and single cell qPCR to determine the correlation between levels of mRNA expression and functional protein expression and how functional properties correlated with the different transcriptional groups. These studies show that although transcriptomics does map to functional types, within any one functional subgroup, there are highly variable patterns of gene expression. Thus, studies that rely on the expression pattern of one or a few genes as a stand in for physiological experiments, runs a high risk of data misinterpretation with respect to function.Significance statementExpression profiles of unidentified sensory neurons have been recently studied using RNASeq techniques. Here, we utilize a multifactorial approach to target identified cutaneous and muscle afferents to examine expression and functional levels of specific high priority candidate genes using ex vivo electrophysiology, Ca2+ imaging, and single cell qPCR. Using this methodology, we were able to identify specific groups of neurons with distinct functional properties that corresponded to unique transcriptional profiles. This represents the first attempt to relate neuronal phenotype with levels of gene expression in single identified afferents and highlights the importance of combining functional analysis with transcriptomics.

Unresolved inflammation is a significant predictor for developing chronic pain, and targeting the mechanisms underlying inflammation offers opportunities for therapeutic intervention. During inflammation, matrix metalloproteinase (MMP) activity contributes to tissue remodeling and inflammatory signaling through proteolytic maturation of cytokines. MMP activity is regulated by tissue inhibitors of metalloproteinases (TIMPs) 1-4. TIMP-1 and −2 have known roles in pain, but only in the context of MMP inhibition. However, TIMP-1 also has receptor-mediated cell signaling functions that are not well understood. Here, we examined how TIMP-1-dependent cell signaling impacted inflammatory hypersensitivity and ongoing pain. We found that hindpaw injection of complete Freund’s adjuvant (CFA) increased keratinocyte-derived TIMP-1 that peaked 3 days following inflammation, when mechanical hypersensitivity began to emerge in WT mice. These data suggest that TIMP-1 expression inhibits the development of inflammatory hypersensitivity. To examine this possibility, we injected TIMP-1 knockout (T1KO) mice with a diluted CFA mixture to examine how subtle cutaneous inflammation affected behavioral hypersensitivity. T1KO mice exhibited rapid onset thermal and mechanical hypersensitivity at the site of inflammation that was absent or attenuated in WT controls. We also found that T1KO mice exhibited hypersensitivity in adjacent tissues innervated by different sets of afferents, and skin contralateral to the site of inflammation. Replacement of recombinant murine (rm)TIMP-1 alleviated hypersensitivity when administered at the site and time of inflammation. To examine the MMP-dependent and -independent mechanisms of rmTIMP-1, T1KO mice were administered full-length rmTIMP-1, the N-terminal region (TIMP-1(N)) with MMP-inhibitory properties, or the C-terminal region (TIMP-1(C)) that retains receptor signaling function. Each of the peptides prevented inflammatory hypersensitivity, suggesting that rmTIMP-1 acts through mechanisms that also include receptor-mediated cell signaling. We also found that hypersensitivity was neither due to genotype-specific differences in MMP-9 activity or expression, nor to differences in cytokine expression. Finally, to evaluate the potential clinical utility of TIMP-1, we administered rmTIMP-1 to WT mice and found that rmTIMP-1 prevented clonidine-induced conditioned place preference (e.g., ongoing pain) and inflammatory mechanical hypersensitivity. Collectively, our data suggest a novel role for TIMP-1 in the attenuation of inflammatory pain that occurs through previously uncharacterized cell signaling mechanisms.

BACKGROUND: Over 90% of women experience pain during breastfeeding initiation and lack strategies to self-manage breast and nipple pain. Guided by the Individual and Family Self-Management Theory (IFSMT), a Breastfeeding Self-Management (BSM) intervention targeted women’s knowledge, beliefs, and social facilitation to manage their breast and nipple pain and achieve their breastfeeding goals. OBJECTIVES: The purpose of this longitudinal pilot randomized control trial (RCT) was to test the preliminary efficacy of the BSM intervention on general and specific pain related to breastfeeding. METHOD: Sixty women intending to breastfeed were approached within 48 hours of delivery to participate in this pilot RCT (30 randomized to BSM intervention and 30 to control group). All participants provided baseline data before discharge, and pain and breastfeeding measures at 1, 2, and 6 weeks. Participants in the BSM intervention group received educational modules addressing breast and nipple pain, biweekly, text-based, nurse coaching, and completed a daily breastfeeding journal. RESULTS: Women in the BSM intervention group reported significantly less breast and nipple pain at 1 and 2 weeks using a visual analogue scale (VAS), p < 0.014, and p < 0.006, and at 2 weeks using the Brief Pain Inventory intensity scale, p < .029, but no difference in breastfeeding duration. DISCUSSION: The BSM intervention pilot demonstrates a positive effect on breastfeeding specific and overall generalized pain. Future investigation is needed to identify at-risk women of ongoing breastfeeding pain, and develop precision interventions to sustain this beneficial health behavior for mothers and infants.

Chronic prostatitis/chronic pelvic pain syndrome causes symptoms that include the frequent and urgent need to urinate, pain or burning during urination and pain radiating to the back, abdomen and/or colorectum. These bladder symptoms suggest that chronic prostatitis/chronic pelvic pain syndrome is associated with sensitization of adjacent organs, termed cross-organ sensitization. The objective of this study was to determine the extent of 1) changes in immunomodulatory mediators in the prostate and bladder after inflammation of the prostate and 2) bladder function and bladder afferent sensitization.Prostate and bladder histology, immunohistochemistry and expression of immunomodulatory targets were examined weekly after zymosan or vehicle was injected in the dorsal lobe of the mouse prostate. Cystometry, bladder and bladder afferent sensitivity were also assessed weekly.Prostate inflammation induced significant up-regulation in proinflammatory and anti-inflammatory cytokines TNF-α (tumor necrosis factor-α) and IL-10 (interleukin-10), growth factor NGF (nerve growth factor), and T-lymphocyte markers FoxP3, CD4 and CD8 in the prostate and the bladder. Notably, prostatitis significantly increased urinary voiding frequency, induced hypersensitivity to bladder distension and sensitized bladder afferents. We also examined sensory (afferent) co-innervation by injecting retrograde tracers DiI and Fast Blue in the bladder wall and the prostate, respectively. This showed that a significant proportion (approximately 17%) of dorsal root ganglion afferent somata contained tracers from the bladder and the prostate.These observations support an afferent contribution to chronic prostatitis/chronic pelvic pain syndrome and cross-organ sensitization from prostate to bladder.

Mechanical sensitivity is commonly affected in chronic pain and other neurological disorders. To discover mechanisms of individual differences in punctate mechanosensation, we performed quantitative trait locus (QTL) mapping of the response to von Frey monofilament stimulation in BXD recombinant inbred (BXD) mice. Significant loci were detected on mouse chromosome (Chr) 5 and 15, indicating the location of underlying polymorphisms that cause heritable variation in von Frey response. Convergent evidence from public gene expression data implicates candidate genes within the loci: von Frey thresholds were strongly correlated with baseline expression of Cacna2d1, Ift27 and Csnk1e in multiple brain regions of BXD strains. Systemic gabapentin and PF-670462, which target the protein products of Cacna2d1 and Csnk1e, respectively, significantly increased von Frey thresholds in a genotype-dependent manner in progenitors and BXD strains. Real-time polymerase chain reaction confirmed differential expression of Cacna2d1 and Csnk1e in multiple brain regions in progenitors and showed differential expression of Cacna2d1 and Csnk1e in the dorsal root ganglia of the progenitors and BXD strains grouped by QTL genotype. Thus, linkage mapping, transcript covariance and pharmacological testing suggest that genetic variation affecting Cacna2d1 and Csnk1e may contribute to individual differences in von Frey filament response. This study implicates Cacna2d1 and Ift27 in basal mechanosensation in line with their previously suspected role in mechanical hypersensitivity. Csnk1e is implicated for von Frey response for the first time. Further investigation is warranted to identify the specific polymorphisms involved and assess the relevance of these findings to clinical conditions of disturbed mechanosensation.

Sunflower seeds are used to produce oil for human consumption, but its protein meal by-product has long been used as animal feed. Formation of green-colored complexes through oxidized chlorogenic acid(CGA)-protein interactions is a primary reason why defatted sunflower protein has not been widely utilized by the food industry. Sunflower protein possesses many properties that make it an appealing alternative protein source from both a marketing and formulation perspective, including its low cost, absence of major allergens, low antitrypsin inhibitors, and its status as both vegan and "clean" label friendly. With the global demand for sunflower oil and novel protein sources expected to increase and waste recovery a concern for many, providing uses for the sunflower meal and its fiber and polyphenol components would provide added value to by-products from sunflower oil processing. This review addresses the unique green pigmentation associated with the interaction of sunflower protein and oxidized CGA by outlining the sunflower oil and protein meal market, CGA reactions contributing to greening, methods for CGA extraction, and the effect of processing on sunflower protein quality and the greening reaction. This review also addresses potential food applications of sunflower protein-based ingredients, such as addition of texturized protein to food products; a microencapsulation matrix for antioxidants; edible, flexible biodegradable films; and even use of sunflower butter as an alternative to peanut butter where the green color is not considered undesirable. Continued studies are needed to make sunflower-based products and CGA-extraction processes available across the global marketplace.

Objective Pain disability is a complex and challenging problem that impacts the daily lives of individuals living with persistent pain. Although this concept is measured throughout pain populations, conceptual clarity is needed to identify the defining characteristics and further understand what comprises this experience for clinical translation. Design We completed a concept analysis to identify major attributes and provide a broad framework of pain disability for improved recognition throughout the discipline of nursing. Data Sources Literature searches in PubMed, CINAHL, PsychINFO, and Scopus identified 39 relevant cross-disciplinary articles published between January 1990 and November 2017. Review/Analysis Methods We implemented Avant and Walker's method of concept analysis to establish the attributes, antecedents, and consequences of pain disability. Results Two major attributes of pain disability are discussed, including (1) physical and/or psychological responses leading to a functional loss; and (2) the degree of ability to fulfill role expectations. The antecedent to the development of pain disability is a painful trigger. Three leading consequences are identified as suffering, pain reactivity, and secondary loss. Conclusions Pain disability is a fluid concept that is characterized by the subjective experiences of the individual. A new conceptualization of pain disability is offered as the inability to maintain role expectations due to the result of a painful trigger and subsequent physical and/or psychosocial dysfunction.

Objectives Chronic postsurgical pain is pain that develops and persists for at least 3 months after a surgical procedure. The purpose of this review was to discover what evidence exists regarding the influence of race and ethnicity on postoperative pain intensity and what evidence exists regarding the influence of genetic polymorphisms on postoperative pain intensity. Design Integrative literature review. Data sources CINAHL, PsychInfo, SCOPUS, and PubMed/Medline databases were searched for entries within the last 10 years. Sources included primary research investigating the relationship among race, ethnicity, and genetics in postoperative pain outcomes. Review/analysis methods Studies adhered to a strict inclusion and exclusion criteria. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were utilized to evaluate and assess manuscripts for inclusion. Results Twelve manuscripts were included for final review. There are significantly higher preoperative and postoperative pain intensity scores reported between African American and Hispanic individuals compared with non-Hispanic whites. Although some studies identified that non-Hispanic whites consumed more opioids and reported increased pain, there were no significant differences in opioid requirements in Hispanic and non-Hispanic individuals. COMT and OPRM1 were the most identified genetic polymorphisms associated with postoperative pain intensity. Conclusions The literature varies with respect to race, ethnicity, and postoperative pain perception. Perioperative pain intensity has been suggested as a significant predictor of chronic postsurgical pain. COMT and OPRM1 may be associated with higher pain perception after surgical procedures.

Objective: To examine changes that occur in infant and parent salivary oxytocin (OT) and salivary cortisol (SC) levels during skin-to-skin contact (SSC) and whether SSC alleviates parental stress and anxiety while also supporting mother–father–infant relationships. Methods: This randomized crossover study was conducted in the neonatal intensive care unit (NICU) with a sample of 28 stable preterm infants and their parents. Saliva samples were collected from infants, mothers, and fathers on Days 1 and 2 (1/parent) for OT and cortisol measurement pre-SSC, during a 60-min SSC session, and a 45-min post-SSC. Parental anxiety was measured at the same time points. Parent–infant interaction was examined prior to discharge on Day 3 via video for synchrony and responsiveness using Dyadic Mutuality Coding. Results: Salivary OT levels increased significantly during SSC for mothers ( p < .001), fathers ( p < .002), and infants ( p < .002). Infant SC levels decreased significantly ( p < .001) during SSC as compared to before and after SSC. Parent anxiety scores were significantly related to parent OT and SC levels. Parents with higher OT levels exhibited more synchrony and responsiveness ( p < .001) in their infant interactions. Conclusion: This study addresses a gap in understanding the mechanisms linking parent–infant contact to biobehavioral responses. SSC activated OT release and decreased infant SC levels. Facilitation of SSC may be an effective intervention to reduce parent and infant stress in the NICU. Findings advance the exploration of OT as a potential moderator for improving responsiveness and synchrony in parent–infant interactions.

As healthcare teams have worked to improve infant survival rates, the management of painful events experienced by these hospitalized neonates has increased and yet pain management remains highly variable between healthcare institutions. At the same time, emerging evidence suggests that these early painful experiences may alter the trajectory of development for pain-processing pathways both peripherally and centrally. This concise review highlights findings from both the basic and clinical science literature supporting the hypothesis that early painful experiences can have long-lasting negative effects on biological, psychological, and socioemotional functions. Implications for pain management in neonates and considerations for evidence-based practice change are discussed.

Infants who begin early life in the medicalized environment of the neonatal intensive care unit (NICU) experience disruption to numerous fundamental expectancies. In the NICU, infants are exposed to chronic, extreme stressors that include painful medical procedures and parental separation. Due to their preverbal stage of development, infants are unable to fully express these experiences, and linking these experiences to long-term outcomes has been difficult. This clinical article proposes the terminology Infant Medical Trauma in the NICU (IMTN) to describe the infant experience. Following a discussion of the NICU as an adverse childhood event, the article has three sections: (a) the unique and critical factors that define the newborn period, (b) a review of the IMTN conceptual model, and (c) recommendations for supportive neuroprotective strategies to moderate the intensity of adverse NICU infant experiences.

Tissue damage results in the release of molecules that aid in tissue repair and produce hypersensitivity. Tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), a protease inhibitor involved in extracellular matrix remodeling, contributes to neuropathic pain, but its role in modulating hypersensitivity during inflammatory conditions remains to be elucidated. To determine how inflammation regulates TIMP-1 expression in the skin we injected complete Freund's adjuvant (CFA) subcutaneously (s.c.) into the dorsal hindpaw of WT mice and found that TIMP-1 protein was significantly increased 1- and 3-dayspost-injection, a time when behavioral hypersensitivity is not observed. Therefore, we hypothesized that the release of TIMP-1 following inflammation attenuates the onset of hypersensitivity. To test this, we used global TIMP-1 knockout (T1KO) mice to examine the development of inflammatory hypersensitivity in the absence of TIMP-1. We found that T1KO mice developed hypersensitivity within 24 hours of inflammation and remained sensitive for 7 days, while WT controls developed hypersensitivity 3 days following inflammation that resolved by day 7. Ex vivo electrophysiological recordings of cutaneous sensory neurons demonstrated that T1KO afferents exhibited greater sensitivity that WT afferents. Analysis of WT and T1KO skin did not detect any genotype-specific differences in MMP-9 activity or inflammatory cytokine expression. Given that the C terminal region of TIMP-1 binds to the CD63/beta 1 Integrin receptor complex, our results suggest that TIMP-1 may attenuate hypersensitivity through a receptor-mediated signaling pathway. To explore this possibility, we injected T1KO mice with a beta 1 integrin inhibitor (Ha2/5) at the time of inflammation. We found that antagonizing beta 1 integrin reversed inflammatory hypersensitivity. Thus, our data suggest that in the absence of TIMP-1 activation of beta 1 integrin contributes to inflammatory hypersensitivity.

Primary afferent nociceptors have been extensively characterized. However, like central neurons, they do not function in isolation. Within the dorsal root ganglia, satellite glial cells (SGCs) ensheath the cell bodies of primary afferents, allowing for bidirectional communication between neurons and SGCs. The mechanisms underlying this bidirectional communication and how SGCs can augment nociceptive signaling are not well understood. Ultimately, to understand the role of SGCs in nociceptive processing we have started developing a cellular profile of SGC-related markers during naive and inflamed states using flow cytometry (FC). To do this, female C57BL/6 mice received subcutaneous injections of Complete Freund's Adjuvant (CFA) or saline vehicle into the hairy skin of the right hind paw of. Behavioral sensitivity to mechanical stimulation was assessed using von Frey filaments at baseline, 2, 7, 14, 21, and 28 days following injection. We found that mice developed hypersensitivity at 7 days compared to vehicle controls. Next, we isolated L1-L3 DRGs at baseline, 2- and 7-days post-CFA for FC. We found that inflamed mice showed increased expression of glial fibrillary acidic protein (GFAP), and the calcium sensing protein, S100, 2 days following inflammation relative to naive controls. Seven days following inflammation we observed a decrease in GFAP, while S100 remained elevated. We also observed upregulation of glutamate converting enzyme, glutamine synthetase (GS), but not until 7 days following inflammation. These data suggest that peripheral inflammation may alter SGC-related markers in a temporally-specific manner that may contribute to hypersensitivity. Ongoing experiments are examining how inflammation impacts the expression of additional SGC-related proteins and genes, as well as the effect of anti-inflammatory administration on SGCs. We expect that our approach will provide an in-depth analysis of SGCs heterogeneity, and identify specific targets that are critical for driving SGC response to inflammation.

Trauma is an innately subjective experience ensuing from a deeply distressing event. Research has demonstrated that while the environment of the neonatal intensive care unit (NICU) is capable of providing extraordinary lifesaving measures following birth, the experience may be disruptive to several key aspects of early development, placing infants at risk for adverse behavioral, cognitive, and emotional outcomes.This article provides rationale for the concept of Infant Medical Trauma in the NICU (IMTN) as a means of describing this unique stress experience. A triad of cumulative early life NICU experiences (stress, parental separation, and pain) is proposed to influence an infant's swinging neurodevelopmental pendulum amid the potential outcomes of risk and resilience.Creating language that describes the infant experience brings meaning and calls caregivers and parents to action to consider strategies that may improve long-term health. Actively seeking opportunities to decrease the allostatic load of at-risk infants may support an infant's pendulum to swing toward a path of resilience, thereby moderating his or her early life adverse experience.

Sunflower seeds are used to produce oil for human consumption, but its protein meal by-product has long been used as animal feed. Formation of green-colored complexes through oxidized chlorogenic acid(CGA)-protein interactions is a primary reason why defatted sunflower protein has not been widely utilized by the food industry. Sunflower protein possesses many properties that make it an appealing alternative protein source from both a marketing and formulation perspective, including its low cost, absence of major allergens, low antitrypsin inhibitors, and its status as both vegan and "clean" label friendly. With the global demand for sunflower oil and novel protein sources expected to increase and waste recovery a concern for many, providing uses for the sunflower meal and its fiber and polyphenol components would provide added value to by-products from sunflower oil processing. This review addresses the unique green pigmentation associated with the interaction of sunflower protein and oxidized CGA by outlining the sunflower oil and protein meal market, CGA reactions contributing to greening, methods for CGA extraction, and the effect of processing on sunflower protein quality and the greening reaction. This review also addresses potential food applications of sunflower protein-based ingredients, such as addition of texturized protein to food products; a microencapsulation matrix for antioxidants; edible, flexible biodegradable films; and even use of sunflower butter as an alternative to peanut butter where the green color is not considered undesirable. Continued studies are needed to make sunflower-based products and CGA-extraction processes available across the global marketplace.