Pub Date : 2023-12-05DOI: 10.3389/fpain.2023.1279420
Yi Lily Zhang, Jun J. Mao, Q. Li, Matthew Weitzman, Kevin T. Liou
Battlefield Acupuncture (BFA), a standardized auricular acupuncture protocol, is widely used for pain in the military but is not well-studied in oncology. This study examined cancer survivors who received BFA for pain.This is a secondary analysis of a randomized trial that compared the effectiveness of BFA and electroacupuncture vs. usual care for chronic musculoskeletal pain in cancer survivors. This study focused on participants randomized to BFA. Participants received 10 weekly treatments. Needles were placed until one of these stop conditions were satisfied: ten needles were administered; pain severity decreased to ≤1 out of 10; patient declined further needling, or vasovagal reaction was observed. Pain severity was assessed using Brief Pain Inventory. Responders were those with ≥30% pain severity reduction. We examined pain location, BFA stop reason, and pain reduction of participants during the first session. We also examined which factors predicted responder status after the first session (week 1) or the full treatment (week 12).Among 143 randomized to BFA, most common pain locations were lower back (30.8%) and knee/leg (18.2%). Of 138 who initiated treatment, 41 (30.0%) received ten needles; 81 (59.1%) achieved pain ≤1; 14 (10.2%) declined further needling; and 1 (0.7%) had vasovagal reaction. BFA reduced pain severity by 2.9 points (95% CI 2.6 to 3.2) after the first session (P < 0.001). After adjusting for baseline pain severity, responders at week 1 were 2.5 times more likely to be responders at week 12, compared to those who were non-responders at week 1 (AOR 2.5, 95% CI 1.02 to 6.11, P = 0.04). Among those who achieved pain ≤1, 74% were responders at week 12, a higher proportion compared to the proportion of responders among those who received ten needles (39.5%), those who declined further needling (50%), and those with vasovagal reaction (0.0%) (P = 0.001). Those with pain in proximal joints had a higher proportion of responders at week 12, compared to those with pain in distal joints (64.2% vs. 20%, P = 0.008).Specific factors may predict the likelihood of achieving meaningful pain reduction from BFA. Understanding these predictors could inform precision pain management and acupuncture delivery models.
战地针灸(BFA)是一种标准化的耳穴针灸治疗方案，在军队中广泛用于治疗疼痛，但在肿瘤学中尚未得到充分研究。这项研究调查了接受BFA治疗疼痛的癌症幸存者。这是对一项随机试验的二次分析，该试验比较了BFA和电针治疗癌症幸存者慢性肌肉骨骼疼痛与常规治疗的有效性。这项研究的重点是随机接受BFA治疗的参与者。参与者每周接受10次治疗。直到满足其中一个停止条件:注射10针;疼痛严重程度降至≤1 / 10;患者谢绝进一步针刺，或观察到血管迷走神经反应。使用简短疼痛量表评估疼痛严重程度。缓解者为疼痛严重程度减轻≥30%的患者。我们检查了疼痛部位、BFA停止原因和参与者在第一阶段的疼痛减轻。我们还检查了在第一次治疗(第1周)或完整治疗(第12周)后预测应答状态的因素。在143名随机接受BFA治疗的患者中，最常见的疼痛部位是下背部(30.8%)和膝盖/腿部(18.2%)。在138名开始治疗的患者中，41名(30.0%)接受了10支针头;81例(59.1%)达到疼痛≤1;14家(10.2%)减少了进一步的针刺;1例(0.7%)有血管迷走神经反应。在第一次治疗后，BFA使疼痛严重程度降低了2.9分(95% CI 2.6 - 3.2) (P < 0.001)。调整基线疼痛严重程度后，与第1周无反应者相比，第1周有反应者在第12周有反应者的可能性是无反应者的2.5倍(AOR 2.5, 95% CI 1.02至6.11,P = 0.04)。在疼痛≤1的患者中，74%的患者在第12周有反应，这一比例高于接受10针治疗的患者(39.5%)、不再针刺的患者(50%)和血管迷走神经反应的患者(0.0%)(P = 0.001)。与远端关节疼痛患者相比，近端关节疼痛患者在第12周的应答比例更高(64.2% vs. 20%， P = 0.008)。特定的因素可以预测从BFA中获得有意义的疼痛减轻的可能性。了解这些预测因素可以为精确的疼痛管理和针灸交付模型提供信息。
{"title":"Battlefield acupuncture for chronic musculoskeletal pain in cancer survivors: a novel care delivery model for oncology acupuncture","authors":"Yi Lily Zhang, Jun J. Mao, Q. Li, Matthew Weitzman, Kevin T. Liou","doi":"10.3389/fpain.2023.1279420","DOIUrl":"https://doi.org/10.3389/fpain.2023.1279420","url":null,"abstract":"Battlefield Acupuncture (BFA), a standardized auricular acupuncture protocol, is widely used for pain in the military but is not well-studied in oncology. This study examined cancer survivors who received BFA for pain.This is a secondary analysis of a randomized trial that compared the effectiveness of BFA and electroacupuncture vs. usual care for chronic musculoskeletal pain in cancer survivors. This study focused on participants randomized to BFA. Participants received 10 weekly treatments. Needles were placed until one of these stop conditions were satisfied: ten needles were administered; pain severity decreased to ≤1 out of 10; patient declined further needling, or vasovagal reaction was observed. Pain severity was assessed using Brief Pain Inventory. Responders were those with ≥30% pain severity reduction. We examined pain location, BFA stop reason, and pain reduction of participants during the first session. We also examined which factors predicted responder status after the first session (week 1) or the full treatment (week 12).Among 143 randomized to BFA, most common pain locations were lower back (30.8%) and knee/leg (18.2%). Of 138 who initiated treatment, 41 (30.0%) received ten needles; 81 (59.1%) achieved pain ≤1; 14 (10.2%) declined further needling; and 1 (0.7%) had vasovagal reaction. BFA reduced pain severity by 2.9 points (95% CI 2.6 to 3.2) after the first session (P < 0.001). After adjusting for baseline pain severity, responders at week 1 were 2.5 times more likely to be responders at week 12, compared to those who were non-responders at week 1 (AOR 2.5, 95% CI 1.02 to 6.11, P = 0.04). Among those who achieved pain ≤1, 74% were responders at week 12, a higher proportion compared to the proportion of responders among those who received ten needles (39.5%), those who declined further needling (50%), and those with vasovagal reaction (0.0%) (P = 0.001). Those with pain in proximal joints had a higher proportion of responders at week 12, compared to those with pain in distal joints (64.2% vs. 20%, P = 0.008).Specific factors may predict the likelihood of achieving meaningful pain reduction from BFA. Understanding these predictors could inform precision pain management and acupuncture delivery models.","PeriodicalId":12641,"journal":{"name":"Frontiers in Pain Research","volume":"69 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138600525","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}
Pub Date : 2023-12-05DOI: 10.3389/fpain.2023.1284103
R. Staud, Melyssa M Godfrey, Patrick W. Stroman
Widespread pain and hyperalgesia are characteristics of chronic musculoskeletal pain conditions, including fibromyalgia syndrome (FM). Despite mixed evidence, there is increasing consensus that these characteristics depend on abnormal pain augmentation and dysfunctional pain inhibition. Our recent investigations of pain modulation with individually adjusted nociceptive stimuli have confirmed the mechanical and thermal hyperalgesia of FM patients but failed to detect abnormalities of pain summation or descending pain inhibition. Furthermore, our functional magnetic resonance imaging evaluations of spinal and brainstem pain processing during application of sensitivity-adjusted heat stimuli demonstrated similar temporal patterns of spinal cord activation in FM and HC participants. However, detailed modeling of brainstem activation showed that BOLD activity during “pain summation” was increased in FM subjects, suggesting differences in brain stem modulation of nociceptive stimuli compared to HC. Whereas these differences in brain stem activation are likely related to the hypersensitivity of FM patients, the overall central pain modulation of FM showed no significant abnormalities. These findings suggest that FM patients are hyperalgesic but modulate nociceptive input as effectively as HC.
{"title":"Fibromyalgia is associated with hypersensitivity but not with abnormal pain modulation: evidence from QST trials and spinal fMRI","authors":"R. Staud, Melyssa M Godfrey, Patrick W. Stroman","doi":"10.3389/fpain.2023.1284103","DOIUrl":"https://doi.org/10.3389/fpain.2023.1284103","url":null,"abstract":"Widespread pain and hyperalgesia are characteristics of chronic musculoskeletal pain conditions, including fibromyalgia syndrome (FM). Despite mixed evidence, there is increasing consensus that these characteristics depend on abnormal pain augmentation and dysfunctional pain inhibition. Our recent investigations of pain modulation with individually adjusted nociceptive stimuli have confirmed the mechanical and thermal hyperalgesia of FM patients but failed to detect abnormalities of pain summation or descending pain inhibition. Furthermore, our functional magnetic resonance imaging evaluations of spinal and brainstem pain processing during application of sensitivity-adjusted heat stimuli demonstrated similar temporal patterns of spinal cord activation in FM and HC participants. However, detailed modeling of brainstem activation showed that BOLD activity during “pain summation” was increased in FM subjects, suggesting differences in brain stem modulation of nociceptive stimuli compared to HC. Whereas these differences in brain stem activation are likely related to the hypersensitivity of FM patients, the overall central pain modulation of FM showed no significant abnormalities. These findings suggest that FM patients are hyperalgesic but modulate nociceptive input as effectively as HC.","PeriodicalId":12641,"journal":{"name":"Frontiers in Pain Research","volume":"103 25","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138599871","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}
Pub Date : 2023-11-14DOI: 10.3389/fpain.2023.1264355
Ulrika Wallbing, Stefan Nilsson, Mari Lundberg, Helena Wigert, Mike K. Kemani
Introduction and aims Chronic pain and symptoms of insomnia affect large numbers of adolescents and early interventions are prioritized. The aim of the current study was to evaluate potential secondary effects of the intervention, Help Overcoming Pain Early (HOPE), on symptoms of insomnia and self-rated health. Methods The study included non-randomized aggregated data from the active and control conditions in a previously conducted randomized controlled trial evaluating the efficacy of HOPE, after the participants in the control condition also had received the intervention. Symptoms of insomnia were assessed with the Minimal Insomnia Symptom Scale and self-rated health was assessed with one item, at the start of the intervention, post intervention, and at a six-month follow-up. Baseline variables included age, gender, pain localization, pain impact, school absence and symptoms of depression (assessed with the Center for Epidemiological Studies Depression Scale for Children). Inferential analyzes were performed using Linear Mixed Models (LMM). Effect sizes were evaluated by calculating Cohen's d . Results There were statistically significant improvements in symptoms of insomnia at the six-month follow-up, and statistically significant improvements in self-rated health at the end of the intervention and at the six-month follow-up. Effect sizes were small across outcomes and assessments. Discussion and conclusion Results illustrated significant but small improvements in symptoms of insomnia and self-rated health in adolescents with chronic pain following the HOPE intervention. Although caution is needed when assessing the findings, results illustrate the potential utility of an accessible brief early intervention in a school context.
{"title":"Help overcoming pain early, a brief person-centred intervention for adolescents with chronic pain in a school setting, may improve symptoms of insomnia","authors":"Ulrika Wallbing, Stefan Nilsson, Mari Lundberg, Helena Wigert, Mike K. Kemani","doi":"10.3389/fpain.2023.1264355","DOIUrl":"https://doi.org/10.3389/fpain.2023.1264355","url":null,"abstract":"Introduction and aims Chronic pain and symptoms of insomnia affect large numbers of adolescents and early interventions are prioritized. The aim of the current study was to evaluate potential secondary effects of the intervention, Help Overcoming Pain Early (HOPE), on symptoms of insomnia and self-rated health. Methods The study included non-randomized aggregated data from the active and control conditions in a previously conducted randomized controlled trial evaluating the efficacy of HOPE, after the participants in the control condition also had received the intervention. Symptoms of insomnia were assessed with the Minimal Insomnia Symptom Scale and self-rated health was assessed with one item, at the start of the intervention, post intervention, and at a six-month follow-up. Baseline variables included age, gender, pain localization, pain impact, school absence and symptoms of depression (assessed with the Center for Epidemiological Studies Depression Scale for Children). Inferential analyzes were performed using Linear Mixed Models (LMM). Effect sizes were evaluated by calculating Cohen's d . Results There were statistically significant improvements in symptoms of insomnia at the six-month follow-up, and statistically significant improvements in self-rated health at the end of the intervention and at the six-month follow-up. Effect sizes were small across outcomes and assessments. Discussion and conclusion Results illustrated significant but small improvements in symptoms of insomnia and self-rated health in adolescents with chronic pain following the HOPE intervention. Although caution is needed when assessing the findings, results illustrate the potential utility of an accessible brief early intervention in a school context.","PeriodicalId":12641,"journal":{"name":"Frontiers in Pain Research","volume":"10 10","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134991131","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}
Pub Date : 2023-11-13DOI: 10.3389/fpain.2023.1239633
Ke Ren, Russel Vickers, Josue Murillo, Nikita B. Ruparel
Orofacial pain remains a significant health issue in the United States. Pain originating from the orofacial region can be composed of a complex array of unique target tissue that contributes to the varying success of pain management. Long-term use of analgesic drugs includes adverse effects such as physical dependence, gastrointestinal bleeding, and incomplete efficacy. The use of mesenchymal stem cells for their pain relieving properties has garnered increased attention. In addition to the preclinical and clinical results showing stem cell analgesia in non-orofacial pain, studies have also shown promising results for orofacial pain treatment. Here we discuss the outcomes of mesenchymal stem cell treatment for pain and compare the properties of stem cells from different tissues of origin. We also discuss the mechanism underlying these analgesic/anti-nociceptive properties, including the role of immune cells and the endogenous opioid system. Lastly, advancements in the methods and procedures to treat patients experiencing orofacial pain with mesenchymal stem cells are also discussed.
{"title":"Revolutionizing orofacial pain management: the promising potential of stem cell therapy","authors":"Ke Ren, Russel Vickers, Josue Murillo, Nikita B. Ruparel","doi":"10.3389/fpain.2023.1239633","DOIUrl":"https://doi.org/10.3389/fpain.2023.1239633","url":null,"abstract":"Orofacial pain remains a significant health issue in the United States. Pain originating from the orofacial region can be composed of a complex array of unique target tissue that contributes to the varying success of pain management. Long-term use of analgesic drugs includes adverse effects such as physical dependence, gastrointestinal bleeding, and incomplete efficacy. The use of mesenchymal stem cells for their pain relieving properties has garnered increased attention. In addition to the preclinical and clinical results showing stem cell analgesia in non-orofacial pain, studies have also shown promising results for orofacial pain treatment. Here we discuss the outcomes of mesenchymal stem cell treatment for pain and compare the properties of stem cells from different tissues of origin. We also discuss the mechanism underlying these analgesic/anti-nociceptive properties, including the role of immune cells and the endogenous opioid system. Lastly, advancements in the methods and procedures to treat patients experiencing orofacial pain with mesenchymal stem cells are also discussed.","PeriodicalId":12641,"journal":{"name":"Frontiers in Pain Research","volume":"54 7","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136283062","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}
Pub Date : 2023-11-09DOI: 10.3389/fpain.2023.1279361
Wally R. Smith, Cecelia R. Valrie, Cheedy Jaja, Martha O. Kenney
Sickle cell disease (SCD) is a prevalent and complex inherited pain disorder that can manifest as acute vaso-occlusive crises (VOC) and/or chronic pain. Despite their known risks, opioids are often prescribed routinely and indiscriminately in managing SCD pain, because it is so often severe and debilitating. Integrative medicine strategies, particularly non-opioid therapies, hold promise in safe and effective management of SCD pain. However, the lack of evidence-based methods for managing SCD pain hinders the widespread implementation of non-opioid therapies. In this review, we acknowledge that implementing personalized pain treatment strategies in SCD, which is a guideline-recommended strategy, is currently fraught with limitations. The full implementation of pharmacological and biobehavioral pain approaches targeting mechanistic pain pathways faces challenges due to limited knowledge and limited financial and personnel support. We recommend personalized medicine, pharmacogenomics, and integrative medicine as aspirational strategies for improving pain care in SCD. As an organizing model that is a comprehensive framework for classifying pain subphenotypes and mechanisms in SCD, and for guiding selection of specific strategies, we present evidence updating pain research pioneer Richard Melzack’s neuromatrix theory of pain. We advocate for using the updated neuromatrix model to subphenotype individuals with SCD, to better select personalized multimodal treatment strategies, and to identify research gaps fruitful for exploration. We present a fairly complete list of currently used pharmacologic and non-pharmacologic SCD pain therapies, classified by their mechanism of action and by their hypothesized targets in the updated neuromatrix model.
{"title":"Precision, integrative medicine for pain management in sickle cell disease","authors":"Wally R. Smith, Cecelia R. Valrie, Cheedy Jaja, Martha O. Kenney","doi":"10.3389/fpain.2023.1279361","DOIUrl":"https://doi.org/10.3389/fpain.2023.1279361","url":null,"abstract":"Sickle cell disease (SCD) is a prevalent and complex inherited pain disorder that can manifest as acute vaso-occlusive crises (VOC) and/or chronic pain. Despite their known risks, opioids are often prescribed routinely and indiscriminately in managing SCD pain, because it is so often severe and debilitating. Integrative medicine strategies, particularly non-opioid therapies, hold promise in safe and effective management of SCD pain. However, the lack of evidence-based methods for managing SCD pain hinders the widespread implementation of non-opioid therapies. In this review, we acknowledge that implementing personalized pain treatment strategies in SCD, which is a guideline-recommended strategy, is currently fraught with limitations. The full implementation of pharmacological and biobehavioral pain approaches targeting mechanistic pain pathways faces challenges due to limited knowledge and limited financial and personnel support. We recommend personalized medicine, pharmacogenomics, and integrative medicine as aspirational strategies for improving pain care in SCD. As an organizing model that is a comprehensive framework for classifying pain subphenotypes and mechanisms in SCD, and for guiding selection of specific strategies, we present evidence updating pain research pioneer Richard Melzack’s neuromatrix theory of pain. We advocate for using the updated neuromatrix model to subphenotype individuals with SCD, to better select personalized multimodal treatment strategies, and to identify research gaps fruitful for exploration. We present a fairly complete list of currently used pharmacologic and non-pharmacologic SCD pain therapies, classified by their mechanism of action and by their hypothesized targets in the updated neuromatrix model.","PeriodicalId":12641,"journal":{"name":"Frontiers in Pain Research","volume":" 14","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135293348","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}
Pub Date : 2023-11-06DOI: 10.3389/fpain.2023.1247313
Teshamae S. Monteith, Alit Stark-Inbar, Sharon Shmuely, Dagan Harris, Sandy Garas, Alon Ironi, Paige Kalika, Samantha L. Irwin
Introduction Migraine is a chronic neurological disease manifesting as attacks of disabling head pain and associated symptoms. Remote electrical neuromodulation (REN) is a non-pharmacological, prescribed, wearable device (Nerivio®). This device has been certified by the FDA for the acute and/or preventive treatment of migraine with or without aura in patients 12 years of age or older. The device is affixed to the user’s arm during 45-min treatment sessions and is operated using a smartphone app. This study (NCT05769322) aims to evaluate whether frequent use of REN for the acute treatment of migraine in adolescents resulted in a reduction in monthly migraine treatment days (MMTD), as previously demonstrated in adults through a dedicated prevention clinical trial (NCT04828707). Methods The study included real-world prospective data from adolescent patients who used REN on at least 10 days every 28-day month, following the REN migraine prevention guideline of an every-other-day pattern. Additional requirements were at least three REN treatment days in each of the two subsequent months. The number of MMTD was used as a proxy measure for the number of monthly migraine days (MMD). The change in MMTD from the first month, taken as a “baseline,” to each of the following months was used to evaluate the presence and size of potential migraine preventive benefits of REN in adolescents. Results A total of 83 adolescents were eligible for analysis. The users were 15.9 ± 1.3 years of age (mean ± SD), and 89% of them were female. The results demonstrated a substantial month-to-month reduction in the mean (±SD) number of REN treatment days from 12.6 (±3.2) MMTD in the first month to 9.0 (±4.8) MMTD in the second month ( p < 0.001), and a further decrease to 7.4 (±4.2) MMTD in the third month ( p < 0.001). This indicates an accumulative reduction of 5.2 (±4.8) mean REN MMTD from the first month to the third month of consecutive REN treatment. The users also reported consistent 2-h acute pain responses in at least 50% of their treated attacks, with 61.9% of the users reported experiencing pain relief, 24.5% reported pain freedom, 67.4% indicated relief in functional disability, and 41.3% reported complete freedom from functional disability. Conclusion The frequent use of REN among adolescents as an acute treatment for migraine attacks resulted in a decrease in the mean number of monthly treatment days in the subsequent months, suggesting that REN may have potential preventive benefits for migraine in this subpopulation.
{"title":"Remote electrical neuromodulation (REN) wearable device for adolescents with migraine: a real-world study of high-frequency abortive treatment suggests preventive effects","authors":"Teshamae S. Monteith, Alit Stark-Inbar, Sharon Shmuely, Dagan Harris, Sandy Garas, Alon Ironi, Paige Kalika, Samantha L. Irwin","doi":"10.3389/fpain.2023.1247313","DOIUrl":"https://doi.org/10.3389/fpain.2023.1247313","url":null,"abstract":"Introduction Migraine is a chronic neurological disease manifesting as attacks of disabling head pain and associated symptoms. Remote electrical neuromodulation (REN) is a non-pharmacological, prescribed, wearable device (Nerivio®). This device has been certified by the FDA for the acute and/or preventive treatment of migraine with or without aura in patients 12 years of age or older. The device is affixed to the user’s arm during 45-min treatment sessions and is operated using a smartphone app. This study (NCT05769322) aims to evaluate whether frequent use of REN for the acute treatment of migraine in adolescents resulted in a reduction in monthly migraine treatment days (MMTD), as previously demonstrated in adults through a dedicated prevention clinical trial (NCT04828707). Methods The study included real-world prospective data from adolescent patients who used REN on at least 10 days every 28-day month, following the REN migraine prevention guideline of an every-other-day pattern. Additional requirements were at least three REN treatment days in each of the two subsequent months. The number of MMTD was used as a proxy measure for the number of monthly migraine days (MMD). The change in MMTD from the first month, taken as a “baseline,” to each of the following months was used to evaluate the presence and size of potential migraine preventive benefits of REN in adolescents. Results A total of 83 adolescents were eligible for analysis. The users were 15.9 ± 1.3 years of age (mean ± SD), and 89% of them were female. The results demonstrated a substantial month-to-month reduction in the mean (±SD) number of REN treatment days from 12.6 (±3.2) MMTD in the first month to 9.0 (±4.8) MMTD in the second month ( p &lt; 0.001), and a further decrease to 7.4 (±4.2) MMTD in the third month ( p &lt; 0.001). This indicates an accumulative reduction of 5.2 (±4.8) mean REN MMTD from the first month to the third month of consecutive REN treatment. The users also reported consistent 2-h acute pain responses in at least 50% of their treated attacks, with 61.9% of the users reported experiencing pain relief, 24.5% reported pain freedom, 67.4% indicated relief in functional disability, and 41.3% reported complete freedom from functional disability. Conclusion The frequent use of REN among adolescents as an acute treatment for migraine attacks resulted in a decrease in the mean number of monthly treatment days in the subsequent months, suggesting that REN may have potential preventive benefits for migraine in this subpopulation.","PeriodicalId":12641,"journal":{"name":"Frontiers in Pain Research","volume":"2020 35","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135637235","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}
Pub Date : 2023-11-02DOI: 10.3389/fpain.2023.1173675
Lisa Isaac, Brittany N. Rosenbloom, Jennifer Tyrrell, Danielle A. Ruskin, Kathryn A. Birnie
The prevention of chronic pain is a key priority in North America and around the world. A novel pediatric Transitional Pain Service (pTPS) at the Hospital for Sick Children was established to address four main areas of need, which the authors will describe in more detail: (1) provide comprehensive multi-modal pain management and prevention techniques to children at-risk for the development of chronic pain, (2) provide opioid stewardship for children at-risk for chronic pain and their families at home after discharge, (3) facilitate continuity of pain care for children across transitions between inpatient and outpatient care settings, and (4) support caregivers to manage their child's pain at home. The pTPS works with healthcare providers, patients, and their families to address these areas of need and improve quality of life. Furthermore the service fills the gap between inpatient acute pain services and outpatient chronic pain services (accessible only once pain has persisted for >3 months). In pediatric patients who experience pain in hospital and who have been prescribed opioids, discharge to home or rehabilitation may represent a vulnerable time in which pain may persist and during which analgesic requirements may change. This offers an important opportunity to address and prevent the development of chronic pain, and to monitor opioids while ensuring alternative pain therapy is available. The authors will outline risk factors for persistent postsurgical pain, the development and implementation of a pTPS, present initial clinical outcomes andsuggest areas for future research in this evolving area of care.
{"title":"Development and expansion of a pediatric transitional pain service to prevent complex chronic pain","authors":"Lisa Isaac, Brittany N. Rosenbloom, Jennifer Tyrrell, Danielle A. Ruskin, Kathryn A. Birnie","doi":"10.3389/fpain.2023.1173675","DOIUrl":"https://doi.org/10.3389/fpain.2023.1173675","url":null,"abstract":"The prevention of chronic pain is a key priority in North America and around the world. A novel pediatric Transitional Pain Service (pTPS) at the Hospital for Sick Children was established to address four main areas of need, which the authors will describe in more detail: (1) provide comprehensive multi-modal pain management and prevention techniques to children at-risk for the development of chronic pain, (2) provide opioid stewardship for children at-risk for chronic pain and their families at home after discharge, (3) facilitate continuity of pain care for children across transitions between inpatient and outpatient care settings, and (4) support caregivers to manage their child's pain at home. The pTPS works with healthcare providers, patients, and their families to address these areas of need and improve quality of life. Furthermore the service fills the gap between inpatient acute pain services and outpatient chronic pain services (accessible only once pain has persisted for &gt;3 months). In pediatric patients who experience pain in hospital and who have been prescribed opioids, discharge to home or rehabilitation may represent a vulnerable time in which pain may persist and during which analgesic requirements may change. This offers an important opportunity to address and prevent the development of chronic pain, and to monitor opioids while ensuring alternative pain therapy is available. The authors will outline risk factors for persistent postsurgical pain, the development and implementation of a pTPS, present initial clinical outcomes andsuggest areas for future research in this evolving area of care.","PeriodicalId":12641,"journal":{"name":"Frontiers in Pain Research","volume":"28 4","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135933930","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}
Immersive virtual reality (VR) is a promising tool to reduce pain in clinical setting. Digital scripts displayed by VR disposals can be enriched by several analgesic interventions, which are widely used to reduce pain. One of these techniques is hypnosis induced through the VR script (VRH) which is facilitated by immersive environment and particularly efficient even for low hypnotizable patients. The aim of this study is to assess the efficacy of a VRH script on experimentally induced cold pain perception (intensity and unpleasantness) and physiological expression. 41 healthy volunteers had been recruited in this within-subjects study. They received 9 stimulations of 20 s (3 non-nociceptive cold; 3 low nociceptive cold and 3 highly nociceptive cold) during a VRH session of 20 min (VRH condition) or without VRH (noVRH condition). Physiological monitoring during the cold pain stimulation protocol consisted of recording heart rate, heart rate variability and respiratory frequency. Maximum cold pain intensity perception, measured through the visual analog scale (VAS) on 10, was of 3.66 ± 1.84 (VAS score/10) in noVRH condition and 2.46 ± 1.54 in VRH (Wilcoxon, p < 0.0001). Considering pain unpleasantness perception, 3.68 ± 2.06 in noVRH and 2.21 ± 1.63 in VRH (Wilcoxon, p < 0.0001). Hypnotizability negatively correlated with the decrease in VAS intensity from noVRH to VRH (Spearman r = −0.45; p = 0.0038). In our sample, we found that 31/41 volunteers (75.6%) displayed a reduction of more than 10% of their VAS pain intensity and unpleasantness scores. Trait anxiety was the best predictor of the VRH responders, as well as heart rate variability. In addition, respiratory rate was diminished under VRH in every subgroup. VRH is an effective tool to reduced pain intensity and unpleasantness in a vast majority of healthy subjects. We further indicate in this study that heart rate variability parameter RMSSD (root mean square of successive differences) is a good predictor of this effect, as well as anxiety as a personality trait (but not state anxiety). Further studies are expected to determine more precisely to whom it will be the most useful to offer tailored, non-pharmacological pain management solutions to patients.
沉浸式虚拟现实(VR)是一种很有前途的减轻临床疼痛的工具。虚拟现实处置器显示的数字脚本可以通过多种镇痛干预来丰富，这些干预被广泛用于减轻疼痛。其中一种技术是通过虚拟现实脚本(VRH)诱导催眠，这种技术在沉浸式环境的促进下，即使对低催眠程度的患者也特别有效。本研究的目的是评估VRH脚本对实验诱导的冷痛感知(强度和不愉快)和生理表达的功效。41名健康志愿者参与了这项研究。受试者接受9次20秒的刺激(3次非伤害性冷刺激;3例低伤害性寒冷和3例高伤害性寒冷)在VRH期间20分钟(VRH条件)或不VRH (noVRH条件)。冷痛刺激期间的生理监测包括记录心率、心率变异性和呼吸频率。10日通过视觉模拟量表(VAS)测量的最大冷痛强度感知，noVRH组为3.66±1.84 (VAS评分/10)，VRH组为2.46±1.54 (Wilcoxon, p <0.0001)。考虑疼痛不愉快感觉，noVRH组为3.68±2.06,VRH组为2.21±1.63 (Wilcoxon, p <0.0001)。可催眠性与从noVRH到VRH的VAS强度下降呈负相关(Spearman r = - 0.45;P = 0.0038)。在我们的样本中，我们发现31/41名志愿者(75.6%)的VAS疼痛强度和不愉快评分降低了10%以上。特质焦虑是VRH应答者以及心率变异性的最佳预测因子。此外，各亚组在VRH下呼吸频率均降低。在绝大多数健康受试者中，VRH是减少疼痛强度和不愉快的有效工具。在这项研究中，我们进一步指出，心率变异性参数RMSSD(连续差异的均方根)是这种影响的一个很好的预测指标，以及焦虑作为一种人格特质(但不是状态焦虑)。进一步的研究有望更准确地确定为患者提供量身定制的非药物疼痛管理解决方案对谁最有用。
{"title":"Virtual reality hypnosis diminishes experimental cold pain and alters autonomic responses","authors":"Claire Terzulli, Chloé Chauvin, Cédric Champagnol Di-Liberti, Sylvain Faisan, Laurent Goffin, Coralie Gianesini, Denis Graff, André Dufour, Edouard Laroche, Eric Salvat, Pierrick Poisbeau","doi":"10.3389/fpain.2023.1237090","DOIUrl":"https://doi.org/10.3389/fpain.2023.1237090","url":null,"abstract":"Immersive virtual reality (VR) is a promising tool to reduce pain in clinical setting. Digital scripts displayed by VR disposals can be enriched by several analgesic interventions, which are widely used to reduce pain. One of these techniques is hypnosis induced through the VR script (VRH) which is facilitated by immersive environment and particularly efficient even for low hypnotizable patients. The aim of this study is to assess the efficacy of a VRH script on experimentally induced cold pain perception (intensity and unpleasantness) and physiological expression. 41 healthy volunteers had been recruited in this within-subjects study. They received 9 stimulations of 20 s (3 non-nociceptive cold; 3 low nociceptive cold and 3 highly nociceptive cold) during a VRH session of 20 min (VRH condition) or without VRH (noVRH condition). Physiological monitoring during the cold pain stimulation protocol consisted of recording heart rate, heart rate variability and respiratory frequency. Maximum cold pain intensity perception, measured through the visual analog scale (VAS) on 10, was of 3.66 ± 1.84 (VAS score/10) in noVRH condition and 2.46 ± 1.54 in VRH (Wilcoxon, p &lt; 0.0001). Considering pain unpleasantness perception, 3.68 ± 2.06 in noVRH and 2.21 ± 1.63 in VRH (Wilcoxon, p &lt; 0.0001). Hypnotizability negatively correlated with the decrease in VAS intensity from noVRH to VRH (Spearman r = −0.45; p = 0.0038). In our sample, we found that 31/41 volunteers (75.6%) displayed a reduction of more than 10% of their VAS pain intensity and unpleasantness scores. Trait anxiety was the best predictor of the VRH responders, as well as heart rate variability. In addition, respiratory rate was diminished under VRH in every subgroup. VRH is an effective tool to reduced pain intensity and unpleasantness in a vast majority of healthy subjects. We further indicate in this study that heart rate variability parameter RMSSD (root mean square of successive differences) is a good predictor of this effect, as well as anxiety as a personality trait (but not state anxiety). Further studies are expected to determine more precisely to whom it will be the most useful to offer tailored, non-pharmacological pain management solutions to patients.","PeriodicalId":12641,"journal":{"name":"Frontiers in Pain Research","volume":"26 4","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135934853","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}
Pub Date : 2023-11-01DOI: 10.3389/fpain.2023.960389
Carolyn A. Fairbanks, Cristina D. Peterson
Throughout history humanity has searched for an optimal approach to the use of opioids that maximizes analgesia while minimizing side effects. This review reflects upon the conceptualization of the opioid receptor and the critical role that the pharmaceutical sciences played in its revelation. Opium-containing formulations have been delivered by various routes of administration for analgesia and other therapeutic indications for millennia. The concept of a distinct site of opium action evolved as practitioners developed innovative delivery methods, such as intravenous administration, to improve therapeutic outcomes. The introduction of morphine and synthetic opioids engendered the prevalent assumption of a common opioid receptor. Through consideration of structure-activity relationships, spatial geometry, and pharmacological differences of known ligands, the idea of multiple opioid receptors emerged. By accessing the high-affinity property of naloxone, the opioid receptor was identified in central and peripheral nervous system tissue. The endogenous opioid neuropeptides were subsequently discovered. Application of mu-, delta-, and kappa- opioid receptor-selective ligands facilitated the pharmacological characterization and distinctions between the three receptors, which were later cloned and sequenced. Opioid receptor signal transduction pathways were described and attributed to specific physiological outcomes. The crystal structures of mu, delta, kappa, and nociceptin/orphanin FQ receptors bound to receptor-selective ligands have been elucidated. Comparison of these structures reveal locations of ligand binding and engagement of signal transduction pathways. Expanding knowledge regarding the structure and actions of the opioid receptor fuels contemporary strategies for driving the activity of opioid receptors toward maximizing therapeutic and minimizing adverse outcomes.
{"title":"The opioid receptor: emergence through millennia of pharmaceutical sciences","authors":"Carolyn A. Fairbanks, Cristina D. Peterson","doi":"10.3389/fpain.2023.960389","DOIUrl":"https://doi.org/10.3389/fpain.2023.960389","url":null,"abstract":"Throughout history humanity has searched for an optimal approach to the use of opioids that maximizes analgesia while minimizing side effects. This review reflects upon the conceptualization of the opioid receptor and the critical role that the pharmaceutical sciences played in its revelation. Opium-containing formulations have been delivered by various routes of administration for analgesia and other therapeutic indications for millennia. The concept of a distinct site of opium action evolved as practitioners developed innovative delivery methods, such as intravenous administration, to improve therapeutic outcomes. The introduction of morphine and synthetic opioids engendered the prevalent assumption of a common opioid receptor. Through consideration of structure-activity relationships, spatial geometry, and pharmacological differences of known ligands, the idea of multiple opioid receptors emerged. By accessing the high-affinity property of naloxone, the opioid receptor was identified in central and peripheral nervous system tissue. The endogenous opioid neuropeptides were subsequently discovered. Application of mu-, delta-, and kappa- opioid receptor-selective ligands facilitated the pharmacological characterization and distinctions between the three receptors, which were later cloned and sequenced. Opioid receptor signal transduction pathways were described and attributed to specific physiological outcomes. The crystal structures of mu, delta, kappa, and nociceptin/orphanin FQ receptors bound to receptor-selective ligands have been elucidated. Comparison of these structures reveal locations of ligand binding and engagement of signal transduction pathways. Expanding knowledge regarding the structure and actions of the opioid receptor fuels contemporary strategies for driving the activity of opioid receptors toward maximizing therapeutic and minimizing adverse outcomes.","PeriodicalId":12641,"journal":{"name":"Frontiers in Pain Research","volume":"2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135325869","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}
Pub Date : 2023-10-31DOI: 10.3389/fpain.2023.1274811
Jennifer Mecklenburg, Sergey A. Shein, Mostafa Malmir, Anahit H. Hovhannisyan, Korri Weldon, Yi Zou, Zhao Lai, Yu-Fang Jin, Shivani Ruparel, Alexei V. Tumanov, Armen N. Akopian
Non-neuronal cells constitute 90%–95% of sensory ganglia. These cells, especially glial and immune cells, play critical roles in the modulation of sensory neurons. This study aimed to identify, profile, and summarize the types of trigeminal ganglion (TG) non-neuronal cells in naïve male mice using published and our own data generated by single-cell RNA sequencing, flow cytometry, and immunohistochemistry. TG has five types of non-neuronal cells, namely, glial, fibroblasts, smooth muscle, endothelial, and immune cells. There is an agreement among publications for glial, fibroblasts, smooth muscle, and endothelial cells. Based on gene profiles, glial cells were classified as myelinated and non-myelinated Schwann cells and satellite glial cells. Mpz has dominant expression in Schwann cells, and Fabp7 is specific for SCG. Two types of Col1a2 + fibroblasts located throughout TG were distinguished. TG smooth muscle and endothelial cells in the blood vessels were detected using well-defined markers. Our study reported three types of macrophages (Mph) and four types of neutrophils (Neu) in TG. Mph were located in the neuronal bodies and nerve fibers and were sub-grouped by unique transcriptomic profiles with Ccr2 , Cx3cr1 , and Iba1 as markers. A comparison of databases showed that type 1 Mph is similar to choroid plexus-low (CP lo ) border-associated Mph (BAMs). Type 2 Mph has the highest prediction score with CP hi BAMs, while type 3 Mph is distinct. S100a8 + Neu were located in the dura surrounding TG and were sub-grouped by clustering and expressions of Csf3r , Ly6G , Ngp , Elane , and Mpo . Integrative analysis of published datasets indicated that Neu-1, Neu-2, and Neu-3 are similar to the brain Neu-1 group, while Neu-4 has a resemblance to the monocyte-derived cells. Overall, the generated and summarized datasets on non-neuronal TG cells showed a unique composition of myeloid cell types in TG and could provide essential and fundamental information for studies on cell plasticity, interactomic networks between neurons and non-neuronal cells, and function during a variety of pain conditions in the head and neck regions.
非神经元细胞占感觉神经节的90%-95%。这些细胞，尤其是神经胶质细胞和免疫细胞，在感觉神经元的调节中起着关键作用。本研究旨在利用已发表的单细胞RNA测序、流式细胞术和免疫组织化学产生的数据和我们自己的数据，鉴定、分析和总结naïve雄性小鼠三叉神经节(TG)非神经元细胞的类型。TG有五种非神经元细胞，即胶质细胞、成纤维细胞、平滑肌细胞、内皮细胞和免疫细胞。在关于神经胶质细胞、成纤维细胞、平滑肌细胞和内皮细胞的出版物中有一致的结论。根据基因谱，将神经胶质细胞分为有髓鞘雪旺细胞和无髓鞘雪旺细胞以及卫星神经胶质细胞。Mpz在雪旺细胞中占主导地位，而Fabp7对SCG具有特异性。两种类型的Col1a2 +成纤维细胞分布在TG。使用明确的标记物检测血管中的TG、平滑肌和内皮细胞。本研究报道TG中存在三种巨噬细胞(Mph)和四种中性粒细胞(Neu)。Mph位于神经元体和神经纤维中，并以Ccr2、Cx3cr1和Iba1作为标记物，通过独特的转录组谱进行亚组。数据库的比较表明，1型Mph与脉络膜丛低(CP lo)边界相关Mph (BAMs)相似。2型Mph对CP hi BAMs的预测得分最高，而3型Mph的预测得分明显。S100a8 + Neu位于TG周围硬脑膜，通过聚类和Csf3r、Ly6G、Ngp、Elane、Mpo的表达进行亚组。对已发表数据集的综合分析表明，neu1、neu2和neu3与脑neu1组相似，而neu4与单核细胞来源的细胞相似。总的来说，生成和总结的非神经元TG细胞数据集显示了TG中髓系细胞类型的独特组成，可以为研究细胞可塑性、神经元和非神经元细胞之间的相互作用网络以及头颈部各种疼痛状况下的功能提供必要和基础的信息。
{"title":"Transcriptional profiles of non-neuronal and immune cells in mouse trigeminal ganglia","authors":"Jennifer Mecklenburg, Sergey A. Shein, Mostafa Malmir, Anahit H. Hovhannisyan, Korri Weldon, Yi Zou, Zhao Lai, Yu-Fang Jin, Shivani Ruparel, Alexei V. Tumanov, Armen N. Akopian","doi":"10.3389/fpain.2023.1274811","DOIUrl":"https://doi.org/10.3389/fpain.2023.1274811","url":null,"abstract":"Non-neuronal cells constitute 90%–95% of sensory ganglia. These cells, especially glial and immune cells, play critical roles in the modulation of sensory neurons. This study aimed to identify, profile, and summarize the types of trigeminal ganglion (TG) non-neuronal cells in naïve male mice using published and our own data generated by single-cell RNA sequencing, flow cytometry, and immunohistochemistry. TG has five types of non-neuronal cells, namely, glial, fibroblasts, smooth muscle, endothelial, and immune cells. There is an agreement among publications for glial, fibroblasts, smooth muscle, and endothelial cells. Based on gene profiles, glial cells were classified as myelinated and non-myelinated Schwann cells and satellite glial cells. Mpz has dominant expression in Schwann cells, and Fabp7 is specific for SCG. Two types of Col1a2 + fibroblasts located throughout TG were distinguished. TG smooth muscle and endothelial cells in the blood vessels were detected using well-defined markers. Our study reported three types of macrophages (Mph) and four types of neutrophils (Neu) in TG. Mph were located in the neuronal bodies and nerve fibers and were sub-grouped by unique transcriptomic profiles with Ccr2 , Cx3cr1 , and Iba1 as markers. A comparison of databases showed that type 1 Mph is similar to choroid plexus-low (CP lo ) border-associated Mph (BAMs). Type 2 Mph has the highest prediction score with CP hi BAMs, while type 3 Mph is distinct. S100a8 + Neu were located in the dura surrounding TG and were sub-grouped by clustering and expressions of Csf3r , Ly6G , Ngp , Elane , and Mpo . Integrative analysis of published datasets indicated that Neu-1, Neu-2, and Neu-3 are similar to the brain Neu-1 group, while Neu-4 has a resemblance to the monocyte-derived cells. Overall, the generated and summarized datasets on non-neuronal TG cells showed a unique composition of myeloid cell types in TG and could provide essential and fundamental information for studies on cell plasticity, interactomic networks between neurons and non-neuronal cells, and function during a variety of pain conditions in the head and neck regions.","PeriodicalId":12641,"journal":{"name":"Frontiers in Pain Research","volume":"232 ","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135870485","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}
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