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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Social Disparities of Pain and Pain Intensity Among Women Diagnosed With Early Stage Breast Cancer

Background: Breast cancer is one of the most commonly diagnosed cancers among women in the United States and pain is the most common side effect of breast cancer and its treatment. Yet, the relationships between social determinants of pain and pain experience/intensity remain under-investigated. We examined the associations between social determinants of pain both at the individual level and the neighborhood level to understand how social conditions are associated with pain perception among early stage breast cancer patients. Methods: We conducted integrated statistical analysis of 1,191 women with early stage breast cancer treated at a large cancer center in Memphis, Tennessee. Combining electronic health records, patient-reported data and census data regarding residential address at the time of first diagnosis, we evaluated the relationships between social determinants and pain perception. Pain responses were self-reported by a patient as a numerical rating scale score at the patient’s initial diagnosis and follow-up clinical visits. We implemented two sets of statistical analyses of the zero-inflated Poisson model and estimated the associations between neighborhood poverty prevalence and breast cancer pain intensity. After adjustment for demographic characteristics, cancer stage, and chemotherapy, pain perception was significantly associated with poverty and blight level of the neighborhood. Results: Among women living in the highest-poverty areas, the odds of reporting pain were 2.48 times higher than those in the lowest-poverty area. Women living in the highest-blight area had 5.43 times higher odds of reporting pain than those in the lowest-blight area. Neighborhood-level social determinants were significantly associated with pain intensity among women diagnosed with early-stage breast cancer. Conclusions: Distressed neighborhood conditions are significantly associated with higher pain perception. Breast cancer patients living in socio-economically disadvantaged neighborhoods and in poor environmental conditions reported higher pain severity compared to patients from less distressed neighborhoods. Therefore, post-diagnosis pain treatment design needs to be tailored to the social determinants of the breast cancer patients.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Multi-Site Observational Study to Assess Biomarkers for Susceptibility or Resilience to Chronic Pain: The Acute to Chronic Pain Signatures (A2CPS) Study Protocol

Chronic pain has become a global health problem contributing to years lived with disability and reduced quality of life. Advances in the clinical management of chronic pain have been limited due to incomplete understanding of the multiple risk factors and molecular mechanisms that contribute to the development of chronic pain. The Acute to Chronic Pain Signatures (A2CPS) Program aims to characterize the predictive nature of biomarkers (brain imaging, high-throughput molecular screening techniques, or “omics,” quantitative sensory testing, patient-reported outcome assessments and functional assessments) to identify individuals who will develop chronic pain following surgical intervention. The A2CPS is a multisite observational study investigating biomarkers and collective biosignatures (a combination of several individual biomarkers) that predict susceptibility or resilience to the development of chronic pain following knee arthroplasty and thoracic surgery. This manuscript provides an overview of data collection methods and procedures designed to standardize data collection across multiple clinical sites and institutions. Pain-related biomarkers are evaluated before surgery and up to 3 months after surgery for use as predictors of patient reported outcomes 6 months after surgery. The dataset from this prospective observational study will be available for researchers internal and external to the A2CPS Consortium to advance understanding of the transition from acute to chronic postsurgical pain.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

A novel methodology to integrate outcomes regarding perioperative pain experience into a composite score: Prediction model development and validation

Abstract Background An integrated score that globally assesses perioperative pain experience and rationally weights each component has not yet been developed. Methods A development dataset specific to adult Chinese patients undergoing orthopaedic surgery was obtained from PAIN OUT (1985 qualified patients of 2244). A more recent validation dataset obeying the same conditions was obtained from the Chinese Anaesthesia Shared‐database Platform (1004 qualified patients of 1032). Outcomes were assessed using the International Pain Outcomes Questionnaire (IPO‐Q), which comprises key patient‐level outcomes of perioperative pain management, including pain experience and perceptions of care. Using principal component analysis and regression models, a composite score (CS) was inferred to integrate pain experience. The discrimination of the CS for dissatisfaction and desire for more pain treatment was compared with that of the worst pain score. Results A CS was developed from the 12 items of the IPO‐Q regarding pain experience. The weight for calculating the CS was worst pain 11, least pain 17, time spent in severe pain 11, interference with activity in bed 9, interference with breathing deeply or coughing 10, interference with sleep 9, anxiety 12, helplessness 12, nausea 0, drowsiness 2, itch 5 and dizziness 2. In external validation, the CS indicated superior discrimination to the worst pain in predicting dissatisfaction ( p < 0.001) and desire for more pain treatment ( p < 0.001). Conclusions This study introduced a methodology to integrate outcomes regarding perioperative pain experience into a CS, which was based on the weight of each item. Significance This novel methodology sheds additional light on the riveting issue of carefully integrating several measures into a composite endpoint, which may be useful for quality improvement purposes when addressing the impact of a change in clinical practice.

Jiang, Bailin↗
DOE OSTI2021

Characterisation of motor cortex organisation in patients with different presentations of persistent low back pain

Abstract Persistence of low back pain is thought to be associated with different underlying pain mechanisms, including ongoing nociceptive input and central sensitisation. We hypothesised that primary motor cortex (M1) representations of back muscles (a measure of motor system adaptation) would differ between pain mechanisms, with more consistent observations in individuals presumed to have an ongoing contribution of nociceptive input consistently related to movement/posture. We tested 28 participants with low back pain sub‐grouped by the presumed underlying pain mechanisms: nociceptive pain, nociplastic pain and a mixed group with features consistent with both. Transcranial magnetic stimulation was used to study M1 organisation of back muscles. M1 maps of multifidus (deep and superficial) and longissimus erector spinae were recorded with fine‐wire electromyography and thoracic erector spinae with surface electromyography. The nociplastic pain group had greater variability in M1 map location (centre of gravity) than other groups ( p < .01), which may suggest less consistency, and perhaps relevance, of motor cortex adaptation for that group. The mixed group had greater overlap of M1 representations between deep/superficial muscles than nociceptive pain (deep multifidus/longissimus: p = .001, deep multifidus/thoracic erector spinae: p = .008) and nociplastic pain (deep multifidus/longissimus: p = .02, deep multifidus/thoracic erector spinae: p = .02) groups. This study provides preliminary evidence of differences in M1 organisation in subgroups of low back pain classified by likely underlying pain mechanisms. Despite the sample size, differences in cortical re‐organisation between subgroups were detected. Differences in M1 organisation in subgroups of low back pain supports tailoring of treatment based on pain mechanism and motor adaptation.

Elgueta‐Cancino, Edith↗
DOE OSTI2018

Intrathecal circHIPK3 shRNA alleviates neuropathic pain in diabetic rats

Highlights: • CircHIPK3 was associated with diabetic neuropathic pain. • Silencing circHIPK3 alleviated neuropathic pain via increasing miR-124. Neuropathic pain is one of the most common diabetic complications and significantly decrease the quality of life. The aetiology of the painful diabetic neuropathic pain is not fully clear. Circular RNAs (circRNAs) have been identified as miRNA sponges and involved in various biological processes, including pain. CircHIPK3 is a circRNA that have been shown to be an oncogene or tumor suppressor to regulate cancer cells growth by sponging multiple miRNAs. However, the role of circHIPK3 in diabetic neuropathic pain remains unknown. The aim of the present study was to elucidate the possible role of circHIPK3 in the control of diabetic neuropathic pain. We found that circHIPK3 are highly abundant in serum from diabetes patients who suffered from neuropathic pain and in dorsal root ganglion from STZ-induced diabetes rats. Upregulation of circHIPK3 was positively associated with grade neuropathic pain in patients with type 2 diabetes. Silencing circHIPK3 alleviated neuropathic pain in diabetic rats, which was involved in neuroinflammation. Further mechanistic investigation demonstrated that circHIPK3 interacted with miR-124 and negatively regulated its expression. MiR-124 inhibitor can reverse circHIPK3 knockdown-mediated alleviation of neuropathic pain and inhibition of neuroinflammation in diabetic rats. We present the first evidence that intrathecal circHIPK3 shRNA treatment can be used to treat neuropathic pain of diabetic rats.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Predicting chronic postsurgical pain: current evidence and a novel program to develop predictive biomarker signatures

Chronic pain affects more than 50 million Americans. Treatments remain inadequate, in large part, because the pathophysiological mechanisms underlying the development of chronic pain remain poorly understood. Pain biomarkers could potentially identify and measure biological pathways and phenotypical expressions that are altered by pain, provide insight into biological treatment targets, and help identify at-risk patients who might benefit from early intervention. Biomarkers are used to diagnose, track, and treat other diseases, but no validated clinical biomarkers exist yet for chronic pain. To address this problem, the National Institutes of Health Common Fund launched the Acute to Chronic Pain Signatures (A2CPS) program to evaluate candidate biomarkers, develop them into biosignatures, and discover novel biomarkers for chronification of pain after surgery. This article discusses candidate biomarkers identified by A2CPS for evaluation, including genomic, proteomic, metabolomic, lipidomic, neuroimaging, psychophysical, psychological, and behavioral measures. Acute to Chronic Pain Signatures will provide the most comprehensive investigation of biomarkers for the transition to chronic postsurgical pain undertaken to date. Data and analytic resources generatedby A2CPS will be shared with the scientific community in hopes that other investigators will extract valuable insights beyond A2CPS’s initial findings. This article will review the identified biomarkers and rationale for including them, the current state of the science on biomarkers of the transition from acute to chronic pain, gaps in the literature, and how A2CPS will address these gaps.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Corpus luteum with ovarian stromal edema is associated with pelvic pain and confusion for ovarian torsion

Purpose: To distinguish the corpus luteum with adjacent ovarian stromal edema as an entity associated with pelvic pain, with confounding ultrasound features that may lead to false-positive diagnosis of ovarian torsion. Methods: This is a blinded, retrospective study of 243 corpora lutea on transvaginal ultrasound. Imaging parameters included ovarian and corpus luteum volumes, central cystic space within the corpus luteum, vascularity around the corpus luteum, peripherally displaced follicles, and complex free fluid. Residual volume (ovarian volume minus corpus luteum volume) was used as a surrogate for ovarian stromal edema. Clinical parameters included age, pregnancy, and location/acuity of pain if present. Concern for ovarian torsion in radiology reports was documented. Results: 51.0% (124/243) of patients presented with pain. Multivariate regression analysis of factors significantly associated with pain (including age, p = 0.001; larger corpus luteum volume, p = 0.002; larger residual volume, p < 0.001; complex free fluid, p = 0.002; and peripherally displaced follicles, p < 0.001) left only increased residual volume as significantly associated with pain [OR 1.02–1.16; p = 0.01]. False-positive concern for ovarian torsion on ultrasound was present in 12.9% (16/124) of patients with pain, associated with enlarged ovaries (p < 0.001) and peripherally displaced follicles (p < 0.001). High correlation between location of pain and side of the corpus luteum was demonstrated in patients with pain < 14 days duration (p < 0.001). Conclusion: Corpus luteum with ovarian stromal edema is associated with pelvic pain and can mimic ovarian torsion on ultrasound. Further research should explore diagnostically useful differences between cases of ovarian torsion and cases of ovarian edema related to corpora lutea.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2024

A multi-ancestry genetic study of pain intensity in 598,339 veterans

Chronic pain is a common problem, with more than one-fifth of adult Americans reporting pain daily or on most days. It adversely affects the quality of life and imposes substantial personal and economic costs. Efforts to treat chronic pain using opioids had a central role in precipitating the opioid crisis. Despite an estimated heritability of 25–50%, the genetic architecture of chronic pain is not well-characterized, in part because studies have largely been limited to samples of European ancestry. To help address this knowledge gap, we conducted a cross-ancestry meta-analysis of pain intensity in 598,339 participants in the Million Veteran Program, which identified 126 independent genetic loci, 69 of which are new. Pain intensity was genetically correlated with other pain phenotypes, level of substance use and substance use disorders, other psychiatric traits, education level and cognitive traits. Integration of the genome-wide association studies findings with functional genomics data shows enrichment for putatively causal genes (n = 142) and proteins (n = 14) expressed in brain tissues, specifically in GABAergic neurons. Drug repurposing analysis identified anticonvulsants, β-blockers and calcium-channel blockers, among other drug groups, as having potential analgesic effects. Our results provide insights into key molecular contributors to the experience of pain and highlight attractive drug targets.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Comparison of Sedoanalgesia Versus Ultrasound-Guided Supraclavicular Brachial Plexus Block for the Prevention of the Pain During Endovascular Treatment of Dysfunctional Hemodialysis Fistulas

Purpose: Although intravenous sedation and analgesia have been widely used as a first choice to relieve pain during treatment of dysfunctional hemodialysis fistulas by interventional radiology, the sedoanalgesic drugs have a considerable risk of respiratory depression, especially in hemodialysis patients. In this study, we compared the utility and efficiency of ultrasound-guided supraclavicular brachial plexus block versus sedoanalgesia for the prevention of pain during endovascular treatment of dysfunctional hemodialysis fistulas Materials and Methods: Patients were randomized into two groups: ultrasound-guided supraclavicular brachial plexus block (n = 34) or sedoanalgesia group (n = 34). A visual analogue scale from no pain (= 0) to worst pain possible (= 10) was used to assess the pain intensity. Patient and operator satisfaction were graded from 0 to 2: 0, not satisfied at all; 1, partially satisfied; 2, satisfied (very well or complete satisfaction). Both groups were compared in terms of pain scores, patient and operator satisfaction as well as complications. Results: The median pain score was significantly lower in the block group compared to the sedoanalgesia group, 0 (0–4) versus 6 (2–10), p = 0.0001. Patient satisfaction and operator satisfaction were significantly higher in the block group than in the sedoanalgesia group (p = 0.0001). Severe oxygen desaturation occurred in five (14.7%) patients following the administration of sedoanalgesia. No side effects or complications related to block procedure occurred in any patient. Conclusion: Ultrasound-guided supraclavicular brachial plexus block has advantages over the sedoanalgesia during endovascular treatment of dysfunctional hemodialysis fistulas. It can provide safe and efficient analgesia with excellent procedural satisfaction in adult hemodialysis patients. Level of Evidence: Level 1 (randomized controlled trial).

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2025

Nanoparticle-mediated antagonism of sustained endosomal signaling of the calcitonin receptor-like receptor provides enhanced and persistent relief of oral cancer pain

By improving the delivery and tumor retention of chemotherapeutics, nanomedicines hold potential for cancer treatment. The usefulness of nanoparticle (NP)-encapsulated analgesics for the cancer pain treatment is comparatively unexplored. We investigated whether NPs encapsulating olcegepant (OCP), an antagonist of the calcitonin receptor-like receptor (CLR) for the calcitonin gene-related peptide (CGRP), effectively relieved oral cancer pain in mice. Because persistent endosomal CLR signaling in Schwann cells mediates craniofacial pain, we reasoned that the predisposition of NPs to accumulate in endosomes could be leveraged to effectively relieve oral cancer pain. By expressing biosensors for activated CLR, Gα proteins and β-arrestins in HEK293T and Schwann cells, we found that CGRP activates CLR signaling first at the plasma membrane and then in early, late and recycling endosomes and the cis- and trans-Golgi apparatus. We synthesized biocompatible NPs encapsulating OCP and fluorophores by integrating hydrophobic ion pairing nanoformulation with Flash NanoPrecipitation. NPs slowly released OCP and accumulated in early endosomes, leading to sustained inhibition of endosomal CLR signaling in HEK293T and Schwann cells. Oral cancers were established in mice, which led to heightened pain-like responses. After intra-tumoral injection, NPs were retained in tumors for at least one week. OCP-loaded NPs almost completely reversed allodynia and hyperalgesia for a prolonged period, whereas unencapsulated OCP had small and transient effects. The NP accumulation in endosomal sites of pain signaling, the sustained release of antagonist, and the retention of NPs in tumors explain their beneficial actions. Thus, NP-encapsulation holds promise for the relief of painful cancers that are inadequately treated by opioids.

Calcitonin gene-related peptide↗
DOE OSTI2018

miR-32-5p-mediated Dusp5 downregulation contributes to neuropathic pain

Highlights: • SNL enhanced miR-32-5p expression. • Downregulation of miR-32-5p suppressed neuropathic pain development in vivo. • miR-32-5p promoted inflammatory cytokines levels in microglial cells in vitro. • Dusp5 is a target gene of miR-32-5p. • The effect of miR-32-5p on neuropathic pain is reversed by Dusp5. Previous studies have demonstrated that microRNAs (miRNAs) play important roles in the pathogenesis of neuropathic pain. In the present study, we found that miR-32-5p was significantly upregulated in rats after spinal nerve ligation (SNL), specifically in the spinal microglia of rats with SNL. Functional assays showed that knockdown of miR-32-5p greatly suppressed mechanical allodynia and heat hyperalgesia, and decreased inflammatory cytokine (IL-1β, TNF-α and IL-6) protein expression in rats after SNL. Similarly, miR-32-5p knockdown alleviated cytokine production in lipopolysaccharide (LPS)-treated spinal microglial cells, whereas its overexpression had the opposite effect. Mechanistic investigations revealed Dual-specificity phosphatase 5 (Dusp5) as a direct target of miR-32-5p, which is involved in the miR-32-5p-mediated effects on neuropathic pain and neuroinflammation. We demonstrated for the first time that miR-32-5p promotes neuroinflammation and neuropathic pain development through regulation of Dusp5. Our findings highlight a novel contribution of miR-32-5p to the process of neuropathic pain, and suggest possibilities for the development of novel therapeutic options for neuropathic pain.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Evidence for lack of direct causality between pain and affective disturbances in a rat peripheral neuropathy model

Chronic pain is frequently accompanied by the manifestation of emotional disturbances and cognitive deficits. While a causality relation between pain and emotional/cognitive disturbances is generally assumed, several observations suggest a temporal dissociation and independent mechanisms. We therefore studied Sprague‐Dawley rats that presented a natural resistance to pain manifestation in a neuropathy model (spared nerve injury [SNI]) and compared their performance in a battery of behavioral paradigms—anxiety, depression and fear memory—with animals that presented a pain phenotype. Afterward, we performed an extensive volumetric analysis across prefrontal, orbitofrontal and insular cortical areas. The majority of SNI animals manifested mechanical allodynia (low threshold [LT]), but 13% were similar to Sham controls (high threshold [HT]). Readouts of spontaneous hypersensivity (paw flinches) were also significantly reduced in HT and correlated with allodynia. To increase the specificity of our findings, we segregated the SNI animals in those with left (SNI‐L) and right (SNI‐R) lesions and the lack of association between pain and behavior still remains. Left‐lesioned animals, independent of the LT or HT phenotype, presented increased anxiety‐like behaviors and decreased well‐being. In contrast, we found that the insular cortex (agranular division) was significantly smaller in HT than in LT. To conclude, pain and emotional disturbances observed following nerve injury are to some extent segregated phenomena. Also, HT and LT SNI presented differences in insular volumes, an area vastly implicated in pain perception, suggesting a supraspinal involvement in the manifestation of these phenotypes.

Guimarães, Marco R.↗
DOE OSTI2019

Pain in percutaneous liver core-needle biopsy: a randomized trial comparing the intercostal and subcostal approaches

Purpose: Effective pain control during and after percutaneous core needle liver biopsy is important with regard to ethical considerations and patient comfort. In this randomized double-blind study, we compared post-biopsy pain in the patients undergoing liver core-needle biopsy using either subcostal or intercostal approaches. Methods: All patients referred for ultrasound-guided CNLB between July 2017 and January 2018 to our interventional radiology department were randomized into two groups. Biopsy was performed through intercostal approach in the first group and through subcostal approach in the second group. The intensity of pain 0, 2, and 4 h after the procedure was compared in two groups using a 100-mm visual analogue scale. All biopsies were performed without procedural IV sedation. If patients’ discomfort demanded administration of IV analgesics during or after the procedure, then the patients were excluded from the study. Results: In patients without routine procedural IV sedation, there was no significant difference in the pain level between the intercostal and subcostal groups immediately after the procedure (p = 0.055), but we found a significant difference in the pain level between the two groups 2 (7.5 mm, p = 0.001) and 4 (2 mm, p = 0.001) h after the procedure. Conclusion: The minimum amount of change in the VAS score that is considered clinically important is 13 mm on a 100-mm scale. Pain differences at 2 and 4 h in the two groups in this study were statistically but not clinically significant. Therefore, the authors suggest the use of subcostal route for ultrasound-guided liver biopsy whenever possible, but the results do not warrant the routine use of post-procedure analgesics in whom biopsy is performed via intercostal route.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Effect of Transcatheter Arterial Microembolization on Phantom Limb Pain Persisting for 17 Years

Phantom limb pain is a frequent consequence of the amputation; currently available treatments are far from satisfactory. The present report describes a case in which transcatheter arterial microembolization had a remarkable curative effect on phantom limb pain persisting for 17 years. The patient began feeling phantom limb sensations and brief intermittent pain following lower limb amputation above the knee in 2001. The frequency, intensity, and duration of the pain increased over time, and it was resistant to conservative treatments. Following transcatheter arterial microembolization in 2018, patient immediately experienced marked improvement. The pain has been infrequent, much less intense, and did not interfere with daily life 6 months posttreatment. Transcatheter arterial microembolization could be an alternative treatment option for phantom limb pain. Level of Evidence: IV, Case Report.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Percutaneous Neurolysis for Pain Management in Oncological Patients

Cancer pain is most commonly classified as nociceptive (somatic or visceral) or neuropathic. Different types of pain or pain syndromes are present in all phases of cancer (early and metastatic) and are inadequately treated in 56% to 82.3% of patients. Percutaneous neurolysis and neuromodulation are feasible and reproducible, efficient (70–80% success rate) and safe (≈ 0.5% mean complication rate) palliative therapies for pain reduction in oncologic patients with refractory pain. Percutaneous neurolysis can be performed either by injection of a chemical agent (phenol or alcohol) or by application of continuous radiofrequency or cryoablation. During chemical neurolysis nerve damage is achieved by means of Wallerian degeneration. A thorough knowledge of neural anatomy and pain transmission pathways is fundamental to appropriate patient and technique selection. Imaging guidance and strict asepsis are prerequisites. The purpose of this article is to describe the basic concepts of percutaneous neurolysis in oncologic patients. Controversies concerning techniques and products will be addressed. Finally, the necessity for an individually tailored approach for the selection of the different techniques and targets will be emphasized.

62 RADIOLOGY AND NUCLEAR MEDICINE↗