C. Churchill, Cristina D. Peterson, K. Kitto, Kelsey R. Pflepsen, L. Belur, R. McIvor, L. Vulchanova, George L. Wilcox, C. Fairbanks
{"title":"Adeno-associated virus-mediated gene transfer of arginine decarboxylase to the central nervous system prevents opioid analgesic tolerance","authors":"C. Churchill, Cristina D. Peterson, K. Kitto, Kelsey R. Pflepsen, L. Belur, R. McIvor, L. Vulchanova, George L. Wilcox, C. Fairbanks","doi":"10.3389/fpain.2023.1269017","DOIUrl":"https://doi.org/10.3389/fpain.2023.1269017","url":null,"abstract":"Agmatine, a decarboxylated form of L-arginine, prevents opioid analgesic tolerance, dependence, and self-administration when given by both central and systemic routes of administration. Endogenous agmatine has been previously detected in the central nervous system. The presence of a biochemical pathway for agmatine synthesis offers the opportunity for site-specific overexpression of the presumptive synthetic enzyme for local therapeutic effects. In the present study, we evaluated the development of opioid analgesic tolerance in ICR-CD1 mice pre-treated with either vehicle control or intrathecally delivered adeno-associated viral vectors (AAV) carrying the gene for human arginine decarboxylase (hADC). Vehicle-treated or AAV-hADC-treated mice were each further divided into two groups which received repeated delivery over three days of either saline or systemically-delivered morphine intended to induce opioid analgesic tolerance. Morphine analgesic dose-response curves were constructed in all subjects on day four using the warm water tail flick assay as the dependent measure. We observed that pre-treatment with AAV-hADC prevented the development of analgesic tolerance to morphine. Peripheral and central nervous system tissues were collected and analyzed for presence of hADC mRNA. In a similar experiment, AAV-hADC pre-treatment prevented the development of analgesic tolerance to a high dose of the opioid neuropeptide endomorphin-2. Intrathecal delivery of anti-agmatine IgG (but not normal IgG) reversed the inhibition of endomorphin-2 analgesic tolerance in AAV-hADC-treated mice. To summarize, we report here the effects of AAV-mediated gene transfer of human ADC (hADC) in models of opioid-induced analgesic tolerance. This study suggests that gene therapy may contribute to reducing opioid analgesic tolerance.","PeriodicalId":12641,"journal":{"name":"Frontiers in Pain Research","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139848435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xinyue Liu, Maja R. Radojčić, Ziye Huang, Baoyi Shi, Ge Li, Lingxiao Chen
{"title":"Antidepressants for chronic pain management: considerations from predictive modeling and personalized medicine perspectives","authors":"Xinyue Liu, Maja R. Radojčić, Ziye Huang, Baoyi Shi, Ge Li, Lingxiao Chen","doi":"10.3389/fpain.2024.1359024","DOIUrl":"https://doi.org/10.3389/fpain.2024.1359024","url":null,"abstract":"","PeriodicalId":12641,"journal":{"name":"Frontiers in Pain Research","volume":"30 38","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139795147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xinyue Liu, Maja R. Radojčić, Ziye Huang, Baoyi Shi, Ge Li, Lingxiao Chen
{"title":"Antidepressants for chronic pain management: considerations from predictive modeling and personalized medicine perspectives","authors":"Xinyue Liu, Maja R. Radojčić, Ziye Huang, Baoyi Shi, Ge Li, Lingxiao Chen","doi":"10.3389/fpain.2024.1359024","DOIUrl":"https://doi.org/10.3389/fpain.2024.1359024","url":null,"abstract":"","PeriodicalId":12641,"journal":{"name":"Frontiers in Pain Research","volume":"23 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139855207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katherine Byrd, Makayla Lund, Yan Pan, Brandon H. Chung, Kaitlyn Child, Danny Fowler, Jared Burns-Martin, Mythili Sanikommu, Hallie Henderson, Caroline Gregory, Regina K. Fleming, Jennifer Yanhua Xie
{"title":"Potential mechanisms for osteopathic manipulative treatment to alleviate migraine-like pain in female rats","authors":"Katherine Byrd, Makayla Lund, Yan Pan, Brandon H. Chung, Kaitlyn Child, Danny Fowler, Jared Burns-Martin, Mythili Sanikommu, Hallie Henderson, Caroline Gregory, Regina K. Fleming, Jennifer Yanhua Xie","doi":"10.3389/fpain.2024.1280589","DOIUrl":"https://doi.org/10.3389/fpain.2024.1280589","url":null,"abstract":"Migraines are the leading cause of disability in the United States, and the use of non-pharmaceutical treatments like osteopathic manipulative treatment (OMT) has shown promise. Despite its potential, the lack of mechanistic understanding has hindered widespread adoption. This study aims to investigate the efficacy of OMT in treating acute migraines and unravel its underlying mechanisms of action.Female rats were subjected to a “two-hit” approach to induce migraine-like pain. This involved bilateral injections of Complete Freund's Adjuvant (CFA) into the trapezius muscle (1st hit) followed by exposure to Umbellulone, a human migraine trigger, on Day 6 post-CFA (2nd hit). Soft tissue and articulatory techniques were applied to the cervical region for acute abortive or repeated prophylactic treatment. Cutaneous allodynia and trigeminal system activation were assessed through behavioral tests and immunohistochemical staining.Following Umbellulone inhalation, CFA-primed rats exhibited periorbital and hind paw allodynia. Immediate application of OMT after Umbellulone inhalation as an abortive treatment partially alleviated cutaneous allodynia. With OMT applied thrice as a prophylactic measure, complete suppression of tactile hypersensitivity was observed. Prophylactic OMT also prevented the increase of c-fos signals in the trigeminal nucleus caudalis and the elevation of calcitonin gene-related peptide expression in trigeminal ganglia induced by CFA and Umbellulone exposure at 2 h post-inhalation.These findings provide mechanistic insights into OMT's migraine-relief potential and underscore its viability as a non-pharmacological avenue for managing migraines.","PeriodicalId":12641,"journal":{"name":"Frontiers in Pain Research","volume":"242 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139862442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katherine Byrd, Makayla Lund, Yan Pan, Brandon H. Chung, Kaitlyn Child, Danny Fowler, Jared Burns-Martin, Mythili Sanikommu, Hallie Henderson, Caroline Gregory, Regina K. Fleming, Jennifer Yanhua Xie
{"title":"Potential mechanisms for osteopathic manipulative treatment to alleviate migraine-like pain in female rats","authors":"Katherine Byrd, Makayla Lund, Yan Pan, Brandon H. Chung, Kaitlyn Child, Danny Fowler, Jared Burns-Martin, Mythili Sanikommu, Hallie Henderson, Caroline Gregory, Regina K. Fleming, Jennifer Yanhua Xie","doi":"10.3389/fpain.2024.1280589","DOIUrl":"https://doi.org/10.3389/fpain.2024.1280589","url":null,"abstract":"Migraines are the leading cause of disability in the United States, and the use of non-pharmaceutical treatments like osteopathic manipulative treatment (OMT) has shown promise. Despite its potential, the lack of mechanistic understanding has hindered widespread adoption. This study aims to investigate the efficacy of OMT in treating acute migraines and unravel its underlying mechanisms of action.Female rats were subjected to a “two-hit” approach to induce migraine-like pain. This involved bilateral injections of Complete Freund's Adjuvant (CFA) into the trapezius muscle (1st hit) followed by exposure to Umbellulone, a human migraine trigger, on Day 6 post-CFA (2nd hit). Soft tissue and articulatory techniques were applied to the cervical region for acute abortive or repeated prophylactic treatment. Cutaneous allodynia and trigeminal system activation were assessed through behavioral tests and immunohistochemical staining.Following Umbellulone inhalation, CFA-primed rats exhibited periorbital and hind paw allodynia. Immediate application of OMT after Umbellulone inhalation as an abortive treatment partially alleviated cutaneous allodynia. With OMT applied thrice as a prophylactic measure, complete suppression of tactile hypersensitivity was observed. Prophylactic OMT also prevented the increase of c-fos signals in the trigeminal nucleus caudalis and the elevation of calcitonin gene-related peptide expression in trigeminal ganglia induced by CFA and Umbellulone exposure at 2 h post-inhalation.These findings provide mechanistic insights into OMT's migraine-relief potential and underscore its viability as a non-pharmacological avenue for managing migraines.","PeriodicalId":12641,"journal":{"name":"Frontiers in Pain Research","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139802532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H. Coslett, Jared Medina, Daria Kliot Goodman, Yuchao Wang, Adam Burkey
{"title":"Can they touch? A novel mental motor imagery task for the assessment of back pain","authors":"H. Coslett, Jared Medina, Daria Kliot Goodman, Yuchao Wang, Adam Burkey","doi":"10.3389/fpain.2023.1189695","DOIUrl":"https://doi.org/10.3389/fpain.2023.1189695","url":null,"abstract":"As motor imagery is informed by the anticipated sensory consequences of action, including pain, we reasoned that motor imagery could provide a useful indicator of chronic back pain. We tested the hypothesis that mental motor imagery regarding body movements can provide a reliable assessment of low back pain.Eighty-five subjects with back pain and forty-five age-matched controls were shown two names of body parts and asked to indicate if they could imagine moving so that the named body parts touched. Three types of imagined movements were interrogated: movements of arms, movements of legs and movements requiring flexion and/or rotation of the low back.Accuracy and reaction times were measured. Subjects with back pain were less likely to indicate that they could touch body parts than age-matched controls. The effect was observed only for those movements that required movement of the low back or legs, suggesting that the effect was not attributable to task difficulty or non-specific effects. There was an effect of pain severity. Compared to subjects with mild pain, subjects with severe pain were significantly less likely to indicate that they could move so that named body parts touched. There was a correlation between pain ratings and impaired performance for stimuli that involved the lower but not upper body.As the Can They Touch task is quick, easy to administer and does not require an explicit judgment of pain severity, it may provide useful information to supplement the assessment of subjects with chronic pain.","PeriodicalId":12641,"journal":{"name":"Frontiers in Pain Research","volume":"59 1-2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139863700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H. Coslett, Jared Medina, Daria Kliot Goodman, Yuchao Wang, Adam Burkey
{"title":"Can they touch? A novel mental motor imagery task for the assessment of back pain","authors":"H. Coslett, Jared Medina, Daria Kliot Goodman, Yuchao Wang, Adam Burkey","doi":"10.3389/fpain.2023.1189695","DOIUrl":"https://doi.org/10.3389/fpain.2023.1189695","url":null,"abstract":"As motor imagery is informed by the anticipated sensory consequences of action, including pain, we reasoned that motor imagery could provide a useful indicator of chronic back pain. We tested the hypothesis that mental motor imagery regarding body movements can provide a reliable assessment of low back pain.Eighty-five subjects with back pain and forty-five age-matched controls were shown two names of body parts and asked to indicate if they could imagine moving so that the named body parts touched. Three types of imagined movements were interrogated: movements of arms, movements of legs and movements requiring flexion and/or rotation of the low back.Accuracy and reaction times were measured. Subjects with back pain were less likely to indicate that they could touch body parts than age-matched controls. The effect was observed only for those movements that required movement of the low back or legs, suggesting that the effect was not attributable to task difficulty or non-specific effects. There was an effect of pain severity. Compared to subjects with mild pain, subjects with severe pain were significantly less likely to indicate that they could move so that named body parts touched. There was a correlation between pain ratings and impaired performance for stimuli that involved the lower but not upper body.As the Can They Touch task is quick, easy to administer and does not require an explicit judgment of pain severity, it may provide useful information to supplement the assessment of subjects with chronic pain.","PeriodicalId":12641,"journal":{"name":"Frontiers in Pain Research","volume":"5 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139803787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melanie Fu, Joanna Shen, Cheryl Gu, Ellina Oliveira, Ellisha Shinchuk, Hannah Isaac, Zacharia Isaac, Danielle L. Sarno, Jennifer L. Kurz, David A. Silbersweig, J. Onnela, Daniel S. Barron
{"title":"The Pain Intervention & Digital Research Program: an operational report on combining digital research with outpatient chronic disease management","authors":"Melanie Fu, Joanna Shen, Cheryl Gu, Ellina Oliveira, Ellisha Shinchuk, Hannah Isaac, Zacharia Isaac, Danielle L. Sarno, Jennifer L. Kurz, David A. Silbersweig, J. Onnela, Daniel S. Barron","doi":"10.3389/fpain.2024.1327859","DOIUrl":"https://doi.org/10.3389/fpain.2024.1327859","url":null,"abstract":"Chronic pain affects up to 28% of U.S. adults, costing ∼$560 billion each year. Chronic pain is an instantiation of the perennial complexity of how to best assess and treat chronic diseases over time, especially in populations where age, medical comorbidities, and socioeconomic barriers may limit access to care. Chronic disease management poses a particular challenge for the healthcare system's transition from fee-for-service to value and risk-based reimbursement models. Remote, passive real-time data from smartphones could enable more timely interventions and simultaneously manage risk and promote better patient outcomes through predicting and preventing costly adverse outcomes; however, there is limited evidence whether remote monitoring is feasible, especially in the case of older patients with chronic pain. Here, we introduce the Pain Intervention and Digital Research (Pain-IDR) Program as a pilot initiative launched in 2022 that combines outpatient clinical care and digital health research. The Pain-IDR seeks to test whether functional status can be assessed passively, through a smartphone application, in older patients with chronic pain. We discuss two perspectives—a narrative approach that describes the clinical settings and rationale behind changes to the operational design, and a quantitative approach that measures patient recruitment, patient experience, and HERMES data characteristics. Since launch, we have had 77 participants with a mean age of 55.52, of which n = 38 have fully completed the 6 months of data collection necessitated to be considered in the study, with an active data collection rate of 51% and passive data rate of 78%. We further present preliminary operational strategies that we have adopted as we have learned to adapt the Pain-IDR to a productive clinical service. Overall, the Pain-IDR has successfully engaged older patients with chronic pain and presents useful insights for others seeking to implement digital phenotyping in other chronic disease settings.","PeriodicalId":12641,"journal":{"name":"Frontiers in Pain Research","volume":"121 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139810095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melanie Fu, Joanna Shen, Cheryl Gu, Ellina Oliveira, Ellisha Shinchuk, Hannah Isaac, Zacharia Isaac, Danielle L. Sarno, Jennifer L. Kurz, David A. Silbersweig, J. Onnela, Daniel S. Barron
{"title":"The Pain Intervention & Digital Research Program: an operational report on combining digital research with outpatient chronic disease management","authors":"Melanie Fu, Joanna Shen, Cheryl Gu, Ellina Oliveira, Ellisha Shinchuk, Hannah Isaac, Zacharia Isaac, Danielle L. Sarno, Jennifer L. Kurz, David A. Silbersweig, J. Onnela, Daniel S. Barron","doi":"10.3389/fpain.2024.1327859","DOIUrl":"https://doi.org/10.3389/fpain.2024.1327859","url":null,"abstract":"Chronic pain affects up to 28% of U.S. adults, costing ∼$560 billion each year. Chronic pain is an instantiation of the perennial complexity of how to best assess and treat chronic diseases over time, especially in populations where age, medical comorbidities, and socioeconomic barriers may limit access to care. Chronic disease management poses a particular challenge for the healthcare system's transition from fee-for-service to value and risk-based reimbursement models. Remote, passive real-time data from smartphones could enable more timely interventions and simultaneously manage risk and promote better patient outcomes through predicting and preventing costly adverse outcomes; however, there is limited evidence whether remote monitoring is feasible, especially in the case of older patients with chronic pain. Here, we introduce the Pain Intervention and Digital Research (Pain-IDR) Program as a pilot initiative launched in 2022 that combines outpatient clinical care and digital health research. The Pain-IDR seeks to test whether functional status can be assessed passively, through a smartphone application, in older patients with chronic pain. We discuss two perspectives—a narrative approach that describes the clinical settings and rationale behind changes to the operational design, and a quantitative approach that measures patient recruitment, patient experience, and HERMES data characteristics. Since launch, we have had 77 participants with a mean age of 55.52, of which n = 38 have fully completed the 6 months of data collection necessitated to be considered in the study, with an active data collection rate of 51% and passive data rate of 78%. We further present preliminary operational strategies that we have adopted as we have learned to adapt the Pain-IDR to a productive clinical service. Overall, the Pain-IDR has successfully engaged older patients with chronic pain and presents useful insights for others seeking to implement digital phenotyping in other chronic disease settings.","PeriodicalId":12641,"journal":{"name":"Frontiers in Pain Research","volume":"47 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139869990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ayurvedic protocols of chronic pain management: spatiotemporality as present moment awareness and embodied time","authors":"Vinita Agarwal","doi":"10.3389/fpain.2024.1327393","DOIUrl":"https://doi.org/10.3389/fpain.2024.1327393","url":null,"abstract":"Temporality is understood as the subjective perception of the flow of chronological time and is a central component of contemporary and integrative medicine approaches. Although temporal dynamics are recognized as central to the processes associated with chronic pain (CP), the temporal management of CP is inadequately understood in pain research.How is temporality conceptualized in Ayurvedic protocols of CP management?.Ayurvedic physicians (N = 10) from India were recruited through purposive and snowball sampling. A semi-structured interview protocol was employed to gather qualitative data focusing on the Ayurvedic protocol employed to treat CP patients. The interviews were audio-recorded, professionally transcribed, and thematically analyzed. Member validation, participant voice, and researcher self-awareness were employed to strengthen reliability and validity.An ontologically grounded thematic exploration of Ayurvedic protocols illustrates that temporality is conceptualized in CP as spatiotemporal present moment awareness (PMA) and embodied time (ET). Spatiotemporality as PMA references an awareness of the relationality of cognitive temporal movement, dosha operations, and their pathophysiological expression in the body. Spatiotemporality as ET is conceptualized as awareness of the expression of time in embodied emotional and psychosocial processes as in the movement of the breath through the body, the movement of body sensations over time, and in their intersection with consciousness.The study findings present an experiential and relational framework situating spatiotemporality ontologically as an organizing principle in CP management. While temporality focuses on the representation of experiences and relations over time, spatiotemporality foregrounds a constructionist approach by centering the embodied spatial cognitive expression of time, consciousness, and subjective experience.","PeriodicalId":12641,"journal":{"name":"Frontiers in Pain Research","volume":"47 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139594984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}