Pub Date : 2024-08-21eCollection Date: 2024-01-01DOI: 10.3389/fpain.2024.1394131
Satoshi Kasahara, Miwako Takahashi, Kaori Takahashi, Taito Morita, Ko Matsudaira, Naoko Sato, Toshimitsu Momose, Shin-Ichi Niwa, Kanji Uchida
Introduction: Nociplastic pain (NP), classified as a third type of pain alongside nociceptive and neuropathic pain, is chronic pain arising from the amplification of nociceptive stimuli through central sensitization, despite the absence of tissue damage, sensory nerve damage, or disease. An important clinical feature of NP is that it is not only associated with pain but also with sensory hypersensitivity to sound and light and cognitive dysfunction, including mood and attention disorders. Recent studies have suggested that depression and developmental disorders, such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), coexist with NP at high frequency. Additionally, cognitive impairment in individuals with NP may be associated with these psychiatric comorbidities. However, to our knowledge, there are no reports on (1) multidimensional evaluation and diagnostic details of abdominal NP in adults with ADHD/ASD; (2) how ADHD drugs and antidepressants are administered when ADHD and depression coexist with NP; and (3) how central sensitization, brain function, and family relationship problems underlying NP are altered by treatments of ADHD and depression.
Case presentation: Herein, we present the case of a 51-year-old woman with abdominal NP. She developed severe right lower abdominal pain and underwent a thorough medical examination; however, the physical, medical cause remained unknown, making treatment challenging. Additionally, she took time off work as she began to complain of insomnia and anxiety. She was referred to our pain center, where a diagnosis of depression, ADHD, and ASD was confirmed, and treatment with ADHD medication was initiated. While ADHD medications alone did not yield sufficient improvement, a combination of methylphenidate and the antidepressant venlafaxine eventually led to improvements in abdominal NP, depression, ADHD symptoms, central sensitization, and family relationship issues. During treatment, cerebral blood flow in the anterior cingulate, prefrontal, and parietal cortices also improved.
Conclusion: The treatment of comorbid depression is important while treating NP, and venlafaxine may be effective, especially in cases of comorbid ADHD/ASD. Screening for developmental disorders and depression is required in patients with abdominal NP.
{"title":"Case Report: Methylphenidate and venlafaxine improved abdominal nociplastic pain in an adult patient with attention deficit hyperactivity disorder, autism spectrum disorder, and comorbid major depression.","authors":"Satoshi Kasahara, Miwako Takahashi, Kaori Takahashi, Taito Morita, Ko Matsudaira, Naoko Sato, Toshimitsu Momose, Shin-Ichi Niwa, Kanji Uchida","doi":"10.3389/fpain.2024.1394131","DOIUrl":"10.3389/fpain.2024.1394131","url":null,"abstract":"<p><strong>Introduction: </strong>Nociplastic pain (NP), classified as a third type of pain alongside nociceptive and neuropathic pain, is chronic pain arising from the amplification of nociceptive stimuli through central sensitization, despite the absence of tissue damage, sensory nerve damage, or disease. An important clinical feature of NP is that it is not only associated with pain but also with sensory hypersensitivity to sound and light and cognitive dysfunction, including mood and attention disorders. Recent studies have suggested that depression and developmental disorders, such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), coexist with NP at high frequency. Additionally, cognitive impairment in individuals with NP may be associated with these psychiatric comorbidities. However, to our knowledge, there are no reports on (1) multidimensional evaluation and diagnostic details of abdominal NP in adults with ADHD/ASD; (2) how ADHD drugs and antidepressants are administered when ADHD and depression coexist with NP; and (3) how central sensitization, brain function, and family relationship problems underlying NP are altered by treatments of ADHD and depression.</p><p><strong>Case presentation: </strong>Herein, we present the case of a 51-year-old woman with abdominal NP. She developed severe right lower abdominal pain and underwent a thorough medical examination; however, the physical, medical cause remained unknown, making treatment challenging. Additionally, she took time off work as she began to complain of insomnia and anxiety. She was referred to our pain center, where a diagnosis of depression, ADHD, and ASD was confirmed, and treatment with ADHD medication was initiated. While ADHD medications alone did not yield sufficient improvement, a combination of methylphenidate and the antidepressant venlafaxine eventually led to improvements in abdominal NP, depression, ADHD symptoms, central sensitization, and family relationship issues. During treatment, cerebral blood flow in the anterior cingulate, prefrontal, and parietal cortices also improved.</p><p><strong>Conclusion: </strong>The treatment of comorbid depression is important while treating NP, and venlafaxine may be effective, especially in cases of comorbid ADHD/ASD. Screening for developmental disorders and depression is required in patients with abdominal NP.</p>","PeriodicalId":73097,"journal":{"name":"Frontiers in pain research (Lausanne, Switzerland)","volume":"5 ","pages":"1394131"},"PeriodicalIF":2.5,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-20eCollection Date: 2024-01-01DOI: 10.3389/fpain.2024.1421709
Jessica K Salwen-Deremer, Jamie M Horrigan, Sarah J Westvold, Jennifer A Haythornthwaite
Objective: Quantitative sensory testing is often used to investigate pain in the context of experimental and clinical research studies. However, many of the devices used for QST protocols are only available in resource rich environments, thereby inadvertently limiting the possible pool of participants. Development of remote protocols for appropriate QST measures has the potential to reduce barriers to participation in research.
Methods: Participants with insomnia and Crohn's disease were recruited as part of a clinical trial. We adapted a remote version of the cold pressor test for use during telehealth-based study assessments. Herein, we present data from the baseline assessments including an assessment of feasibility and acceptability of the task.
Results: 100% of participants (N = 28) were able to complete the remote cold pressor test using a combination of materials from their homes and mailed by the study team. Temperature changes during the test were minimal and fairly evenly balanced between increases and decreases. Correlations between submersion time and both general and disease specific pain trended toward significance.
Conclusions: We demonstrated that a remote version of the cold pressor test is feasible and acceptable in a clinical population and provided a step-by-step protocol for administration to facilitate use in other studies.
{"title":"Feasibility and acceptability of remote administration of the cold pressor test.","authors":"Jessica K Salwen-Deremer, Jamie M Horrigan, Sarah J Westvold, Jennifer A Haythornthwaite","doi":"10.3389/fpain.2024.1421709","DOIUrl":"10.3389/fpain.2024.1421709","url":null,"abstract":"<p><strong>Objective: </strong>Quantitative sensory testing is often used to investigate pain in the context of experimental and clinical research studies. However, many of the devices used for QST protocols are only available in resource rich environments, thereby inadvertently limiting the possible pool of participants. Development of remote protocols for appropriate QST measures has the potential to reduce barriers to participation in research.</p><p><strong>Methods: </strong>Participants with insomnia and Crohn's disease were recruited as part of a clinical trial. We adapted a remote version of the cold pressor test for use during telehealth-based study assessments. Herein, we present data from the baseline assessments including an assessment of feasibility and acceptability of the task.</p><p><strong>Results: </strong>100% of participants (<i>N</i> = 28) were able to complete the remote cold pressor test using a combination of materials from their homes and mailed by the study team. Temperature changes during the test were minimal and fairly evenly balanced between increases and decreases. Correlations between submersion time and both general and disease specific pain trended toward significance.</p><p><strong>Conclusions: </strong>We demonstrated that a remote version of the cold pressor test is feasible and acceptable in a clinical population and provided a step-by-step protocol for administration to facilitate use in other studies.</p>","PeriodicalId":73097,"journal":{"name":"Frontiers in pain research (Lausanne, Switzerland)","volume":"5 ","pages":"1421709"},"PeriodicalIF":2.5,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-05eCollection Date: 2024-01-01DOI: 10.3389/fpain.2024.1415635
Robert C Wiederien, Dan Wang, Laura A Frey-Law
Background: While numeric scales to represent pain intensity have been well validated, individuals use various conceptualizations when assigning a number to pain intensity, referred to as pain rating schema. The 18-item Pain Schema Inventory (PSI-18) quantifies pain rating schema by asking for numeric values for multiple mild, moderate or severe pain conditions. This study aimed to assess the validity and reliability of a shortened form of the PSI, using only 6 items (PSI-6).
Methods: A secondary analysis was performed on two existing datasets. The first (n = 641) involved a community-based population that completed the PSI-18. The second (n = 182) included participants with chronic pain who completed the PSI-6 twice, one week apart. We assessed face validity, convergent validity, offset biases, test-retest reliability, and internal consistency of the PSI-6 compared to the PSI-18.
Results: Both the PSI-18 and PSI-6 demonstrated excellent face validity. The PSI-6 demonstrated excellent convergent validity relative to the PSI-18, with correlations from r = 0.88 to 0.92. Bland-Altman plots revealed offset biases near zero (< 0.22 on 0-10 scale) across all categories of mild, moderate, severe and average pain. Internal consistency was excellent, with Cronbach's Alpha = 0.91 and 0.80, for PSI-18 and PSI-6 respectively. Test-retest reliability of the PSI-6 was high with correlations from r = 0.70-0.76.
Conclusion: The PSI-6 is a valid and reliable tool to assess pain rating schema with reduced subject burden, to better interpret individuals' pain ratings and adjust for inter-individual variability.
{"title":"Assessing how individuals conceptualize numeric pain ratings: validity and reliability of the Pain Schema Inventory (PSI-6) Short Form.","authors":"Robert C Wiederien, Dan Wang, Laura A Frey-Law","doi":"10.3389/fpain.2024.1415635","DOIUrl":"10.3389/fpain.2024.1415635","url":null,"abstract":"<p><strong>Background: </strong>While numeric scales to represent pain intensity have been well validated, individuals use various conceptualizations when assigning a number to pain intensity, referred to as pain rating schema. The 18-item Pain Schema Inventory (PSI-18) quantifies pain rating schema by asking for numeric values for multiple mild, moderate or severe pain conditions. This study aimed to assess the validity and reliability of a shortened form of the PSI, using only 6 items (PSI-6).</p><p><strong>Methods: </strong>A secondary analysis was performed on two existing datasets. The first (<i>n</i> = 641) involved a community-based population that completed the PSI-18. The second (<i>n</i> = 182) included participants with chronic pain who completed the PSI-6 twice, one week apart. We assessed face validity, convergent validity, offset biases, test-retest reliability, and internal consistency of the PSI-6 compared to the PSI-18.</p><p><strong>Results: </strong>Both the PSI-18 and PSI-6 demonstrated excellent face validity. The PSI-6 demonstrated excellent convergent validity relative to the PSI-18, with correlations from r = 0.88 to 0.92. Bland-Altman plots revealed offset biases near zero (< 0.22 on 0-10 scale) across all categories of mild, moderate, severe and average pain. Internal consistency was excellent, with Cronbach's Alpha = 0.91 and 0.80, for PSI-18 and PSI-6 respectively. Test-retest reliability of the PSI-6 was high with correlations from r = 0.70-0.76.</p><p><strong>Conclusion: </strong>The PSI-6 is a valid and reliable tool to assess pain rating schema with reduced subject burden, to better interpret individuals' pain ratings and adjust for inter-individual variability.</p>","PeriodicalId":73097,"journal":{"name":"Frontiers in pain research (Lausanne, Switzerland)","volume":"5 ","pages":"1415635"},"PeriodicalIF":2.5,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11330879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142006082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-05eCollection Date: 2024-01-01DOI: 10.3389/fpain.2024.1454278
Sienna K Perry, Joshua J Emrick
[This corrects the article DOI: 10.3389/fpain.2024.1374929.].
[此处更正了文章 DOI:10.3389/fpain.2024.1374929]。
{"title":"Corrigendum: Trigeminal somatosensation in the temporomandibular joint and associated disorders.","authors":"Sienna K Perry, Joshua J Emrick","doi":"10.3389/fpain.2024.1454278","DOIUrl":"https://doi.org/10.3389/fpain.2024.1454278","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fpain.2024.1374929.].</p>","PeriodicalId":73097,"journal":{"name":"Frontiers in pain research (Lausanne, Switzerland)","volume":"5 ","pages":"1454278"},"PeriodicalIF":2.5,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11258022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01eCollection Date: 2024-01-01DOI: 10.3389/fpain.2024.1386573
Alisa J Johnson, Jessica A Peterson, Heather K Vincent, Todd Manini, Yenisel Cruz-Almeida
Introduction: Chronic musculoskeletal (MSK) pain is prevalent in older adults and confers significant risk for loss of independence and low quality of life. While obesity is considered a risk factor for developing chronic MSK pain, both high and low body mass index (BMI) have been associated with greater pain reporting in older adults. Measures of body composition that distinguish between fat mass and lean mass may help to clarify the seemingly contradictory associations between BMI and MSK pain in this at-risk group.
Methods: Twenty-four older adults (mean age: 78.08 ± 5.1 years) completed dual-energy x-ray absorptiometry (DEXA), and pain measures (Graded Chronic Pain Scale, number of anatomical pain sites, pressure pain threshold, mechanical temporal summation). Pearson correlations and multiple liner regression examined associations between body mass index (BMI), body composition indices, and pain.
Results: Significant positive associations were found between number of pain sites and BMI (b = 0.37) and total fat mass (b = 0.42), accounting for age and sex. Total body lean mass was associated with pressure pain sensitivity (b = 0.65), suggesting greater lean mass is associated with less mechanical pain sensitivity.
Discussion: The results from this exploratory pilot study indicate lean mass may provide additional resilience to maladaptive changes in pain processing in older adults, and highlights the importance of distinguishing body composition indices from overall body mass index to better understand the complex relationship between obesity and MSK pain in older adults.
{"title":"Body composition and body mass index are independently associated with widespread pain and experimental pain sensitivity in older adults: a pilot investigation.","authors":"Alisa J Johnson, Jessica A Peterson, Heather K Vincent, Todd Manini, Yenisel Cruz-Almeida","doi":"10.3389/fpain.2024.1386573","DOIUrl":"10.3389/fpain.2024.1386573","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic musculoskeletal (MSK) pain is prevalent in older adults and confers significant risk for loss of independence and low quality of life. While obesity is considered a risk factor for developing chronic MSK pain, both high and low body mass index (BMI) have been associated with greater pain reporting in older adults. Measures of body composition that distinguish between fat mass and lean mass may help to clarify the seemingly contradictory associations between BMI and MSK pain in this at-risk group.</p><p><strong>Methods: </strong>Twenty-four older adults (mean age: 78.08 ± 5.1 years) completed dual-energy x-ray absorptiometry (DEXA), and pain measures (Graded Chronic Pain Scale, number of anatomical pain sites, pressure pain threshold, mechanical temporal summation). Pearson correlations and multiple liner regression examined associations between body mass index (BMI), body composition indices, and pain.</p><p><strong>Results: </strong>Significant positive associations were found between number of pain sites and BMI (<i>b = </i>0.37) and total fat mass (<i>b </i>= 0.42), accounting for age and sex. Total body lean mass was associated with pressure pain sensitivity (<i>b </i>= 0.65), suggesting greater lean mass is associated with less mechanical pain sensitivity.</p><p><strong>Discussion: </strong>The results from this exploratory pilot study indicate lean mass may provide additional resilience to maladaptive changes in pain processing in older adults, and highlights the importance of distinguishing body composition indices from overall body mass index to better understand the complex relationship between obesity and MSK pain in older adults.</p>","PeriodicalId":73097,"journal":{"name":"Frontiers in pain research (Lausanne, Switzerland)","volume":"5 ","pages":"1386573"},"PeriodicalIF":2.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11250474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141629373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-28eCollection Date: 2024-01-01DOI: 10.3389/fpain.2024.1388837
Paolo Bossi, Tatiana Pietrzyńska, César Margarit Ferri, Irene Mansilla, Valeria Tellone, Sara Fioravanti, Giorgio Di Loreto, Alessandro Comandini
Introduction: This study aimed to assess the percentage of patients treated according to the European Society for Medical Oncology (ESMO) 2018 guidelines for breakthrough cancer pain (BTcP) and the impact of guidelines adherence on patients' quality of life (QoL).
Methods: Adult opioid-tolerant patients diagnosed with BTcP and locally advanced or recurrent metastatic cancer with a life expectancy of >3 months prospectively were included. Patients were followed up for 28 days.
Results: Of 127 patients included, 37 were excluded due to the impossibility to establish adherence to the ESMO guidelines. Among the evaluable patients [51.1% female; with mean (SD) age of 66.4 (11.8) years], all were adherent. BTcP was diagnosed by the Association for Palliative Medicine algorithm in 47.8% of patients and by clinical experience in 52.2% of patients. The mean number of daily BTcP episodes ranged between 1 and 8, with a mean (95% CI) severity of 7.3 (7.0; 7.6) at week 0 and 6.2 (5.8; 6.6) at week 4. Time to maximum pain intensity was 3-15 min in 52.2% of patients, and BTcP lasted 30-60 min in 14.4% of patients at week 0 and 4.4% of patients at week 4. Mean (95% CI) treatment effectiveness was 6.6 (6.1; 7.1) at week 0 and 7.4 (7.0; 7.8) at week 4. Median (Q1-Q3) patients' global impression of clinical condition was 4.0 (4.0-4.0) at week 0 and 3.0 (2.0-3.0) at week 4.
Conclusion: A clear BTcP assessment and strict follow-up could be crucial to guidelines adherence and for patient's QoL.
{"title":"Compliance with the breakthrough cancer pain European guidelines and impact on patients' quality of life: an observational prospective study.","authors":"Paolo Bossi, Tatiana Pietrzyńska, César Margarit Ferri, Irene Mansilla, Valeria Tellone, Sara Fioravanti, Giorgio Di Loreto, Alessandro Comandini","doi":"10.3389/fpain.2024.1388837","DOIUrl":"10.3389/fpain.2024.1388837","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to assess the percentage of patients treated according to the European Society for Medical Oncology (ESMO) 2018 guidelines for breakthrough cancer pain (BTcP) and the impact of guidelines adherence on patients' quality of life (QoL).</p><p><strong>Methods: </strong>Adult opioid-tolerant patients diagnosed with BTcP and locally advanced or recurrent metastatic cancer with a life expectancy of >3 months prospectively were included. Patients were followed up for 28 days.</p><p><strong>Results: </strong>Of 127 patients included, 37 were excluded due to the impossibility to establish adherence to the ESMO guidelines. Among the evaluable patients [51.1% female; with mean (SD) age of 66.4 (11.8) years], all were adherent. BTcP was diagnosed by the Association for Palliative Medicine algorithm in 47.8% of patients and by clinical experience in 52.2% of patients. The mean number of daily BTcP episodes ranged between 1 and 8, with a mean (95% CI) severity of 7.3 (7.0; 7.6) at week 0 and 6.2 (5.8; 6.6) at week 4. Time to maximum pain intensity was 3-15 min in 52.2% of patients, and BTcP lasted 30-60 min in 14.4% of patients at week 0 and 4.4% of patients at week 4. Mean (95% CI) treatment effectiveness was 6.6 (6.1; 7.1) at week 0 and 7.4 (7.0; 7.8) at week 4. Median (Q1-Q3) patients' global impression of clinical condition was 4.0 (4.0-4.0) at week 0 and 3.0 (2.0-3.0) at week 4.</p><p><strong>Conclusion: </strong>A clear BTcP assessment and strict follow-up could be crucial to guidelines adherence and for patient's QoL.</p>","PeriodicalId":73097,"journal":{"name":"Frontiers in pain research (Lausanne, Switzerland)","volume":"5 ","pages":"1388837"},"PeriodicalIF":2.5,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11239570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-24eCollection Date: 2024-01-01DOI: 10.3389/fpain.2024.1424348
Panjamurthy Kuppusamy, Md Mamunul Haque, Richard J Traub, Ohannes K Melemedjian
Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect of cancer treatment that significantly impacts patients' quality of life. This study investigated the effects of targeting metabolic pathways on bortezomib-induced neuropathic pain and tumor growth using a Lewis lung carcinoma (LLC) mouse model, while exploring potential sex differences.
Methods: Male and female C57BL/6J mice were implanted with LLC cells and treated with bortezomib alone or in combination with metformin, dichloroacetate (DCA), or oxamate. Tactile allodynia was assessed using von Frey filaments. Tumor volume and weight were measured to evaluate tumor growth.
Results: Metformin, DCA, and oxamate effectively attenuated bortezomib-induced neuropathic pain without compromising the anticancer efficacy of bortezomib in both male and female mice. The LLC model exhibited a paraneoplastic neuropathy-like phenotype. Significant sex differences were observed, with male mice exhibiting larger tumors compared to females. Oxamate was more effective in alleviating allodynia in males, while metformin and DCA showed greater efficacy in reducing tumor growth in females.
Discussion: Targeting metabolic pathways can alleviate CIPN without interfering with bortezomib's anticancer effects. The LLC model may serve as a tool for studying paraneoplastic neuropathy. Sex differences in tumor growth and response to metabolic interventions highlight the importance of considering sex as a biological variable in preclinical and clinical studies investigating cancer biology, CIPN, and potential therapeutic interventions.
{"title":"Targeting metabolic pathways alleviates bortezomib-induced neuropathic pain without compromising anticancer efficacy in a sex-specific manner.","authors":"Panjamurthy Kuppusamy, Md Mamunul Haque, Richard J Traub, Ohannes K Melemedjian","doi":"10.3389/fpain.2024.1424348","DOIUrl":"10.3389/fpain.2024.1424348","url":null,"abstract":"<p><strong>Introduction: </strong>Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect of cancer treatment that significantly impacts patients' quality of life. This study investigated the effects of targeting metabolic pathways on bortezomib-induced neuropathic pain and tumor growth using a Lewis lung carcinoma (LLC) mouse model, while exploring potential sex differences.</p><p><strong>Methods: </strong>Male and female C57BL/6J mice were implanted with LLC cells and treated with bortezomib alone or in combination with metformin, dichloroacetate (DCA), or oxamate. Tactile allodynia was assessed using von Frey filaments. Tumor volume and weight were measured to evaluate tumor growth.</p><p><strong>Results: </strong>Metformin, DCA, and oxamate effectively attenuated bortezomib-induced neuropathic pain without compromising the anticancer efficacy of bortezomib in both male and female mice. The LLC model exhibited a paraneoplastic neuropathy-like phenotype. Significant sex differences were observed, with male mice exhibiting larger tumors compared to females. Oxamate was more effective in alleviating allodynia in males, while metformin and DCA showed greater efficacy in reducing tumor growth in females.</p><p><strong>Discussion: </strong>Targeting metabolic pathways can alleviate CIPN without interfering with bortezomib's anticancer effects. The LLC model may serve as a tool for studying paraneoplastic neuropathy. Sex differences in tumor growth and response to metabolic interventions highlight the importance of considering sex as a biological variable in preclinical and clinical studies investigating cancer biology, CIPN, and potential therapeutic interventions.</p>","PeriodicalId":73097,"journal":{"name":"Frontiers in pain research (Lausanne, Switzerland)","volume":"5 ","pages":"1424348"},"PeriodicalIF":2.5,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11228363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-24eCollection Date: 2024-01-01DOI: 10.3389/fpain.2024.1346694
Daniel Wolfe, Brent Rosenstein, Maryse Fortin
Introduction: Chronic low back pain (CLBP) is the leading cause of years lived with disability worldwide. Transcutaneous electrotherapies have been widely used to treat CLBP but, with the partial exception of transcutaneous electrical nerve stimulation (TENS), their effect on pain, disability, quality-of-life, and psychosocial outcomes have not been systematically reviewed. The purpose of this systematic review and meta-analysis was to clarify the overall effect of transcutaneous electrotherapies on patient-reported outcome measures (PROMs) in CLBP patients.
Methods: Four databases and two study registries were searched for studies that utilized transcutaneous electrotherapies as a primary intervention for CLBP, compared against active or passive controls. Two reviewers independently extracted study data and assessed risk of bias. Studies were grouped by intervention vs. comparison, and by time of follow-up. Meta-analyses were conducted where appropriate.
Results: A total of 89 full-text were assessed for eligibility; 14 studies were included, with 6 in the meta-analyses (all TENS or mixed TENS). Pain: meta-analyses revealed no significant difference for TENS vs. active control, TENS vs. passive control, or mixed TENS vs. active control at post-intervention, nor for mixed TENS vs. active control at 1-month post-intervention. Interferential current (IFC) was more effective than active control (2 studies), while electromyostimulation (EMS) was generally superior to passive, but not active, controls (6 studies).
Disability: Meta-analyses revealed no significant difference for TENS vs. active control at post-intervention, mixed TENS vs. active control at post-intervention, or mixed TENS vs. active control at 1-month post-intervention. IFC was more effective than active control (2 studies), while the EMS results were mixed (6 studies). We were unable to perform meta-analyses for quality-of-life or psychosocial outcomes.
Conclusion: There is moderate evidence that TENS is similar to all controls for improving pain and disability. There is limited evidence that IFC is superior to active controls for improving pain and disability. There is limited evidence that EMS is superior to passive but not active controls for improving pain, and similar to all controls for improving disability.
{"title":"The effect of EMS, IFC, and TENS on patient-reported outcome measures for chronic low back pain: a systematic review and meta-analysis.","authors":"Daniel Wolfe, Brent Rosenstein, Maryse Fortin","doi":"10.3389/fpain.2024.1346694","DOIUrl":"10.3389/fpain.2024.1346694","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic low back pain (CLBP) is the leading cause of years lived with disability worldwide. Transcutaneous electrotherapies have been widely used to treat CLBP but, with the partial exception of transcutaneous electrical nerve stimulation (TENS), their effect on pain, disability, quality-of-life, and psychosocial outcomes have not been systematically reviewed. The purpose of this systematic review and meta-analysis was to clarify the overall effect of transcutaneous electrotherapies on patient-reported outcome measures (PROMs) in CLBP patients.</p><p><strong>Methods: </strong>Four databases and two study registries were searched for studies that utilized transcutaneous electrotherapies as a primary intervention for CLBP, compared against active or passive controls. Two reviewers independently extracted study data and assessed risk of bias. Studies were grouped by intervention vs. comparison, and by time of follow-up. Meta-analyses were conducted where appropriate.</p><p><strong>Results: </strong>A total of 89 full-text were assessed for eligibility; 14 studies were included, with 6 in the meta-analyses (all TENS or mixed TENS). Pain: meta-analyses revealed no significant difference for TENS vs. active control, TENS vs. passive control, or mixed TENS vs. active control at post-intervention, nor for mixed TENS vs. active control at 1-month post-intervention. Interferential current (IFC) was more effective than active control (2 studies), while electromyostimulation (EMS) was generally superior to passive, but not active, controls (6 studies).</p><p><strong>Disability: </strong>Meta-analyses revealed no significant difference for TENS vs. active control at post-intervention, mixed TENS vs. active control at post-intervention, or mixed TENS vs. active control at 1-month post-intervention. IFC was more effective than active control (2 studies), while the EMS results were mixed (6 studies). We were unable to perform meta-analyses for quality-of-life or psychosocial outcomes.</p><p><strong>Conclusion: </strong>There is <i>moderate</i> evidence that TENS is similar to all controls for improving pain and disability. There is <i>limited</i> evidence that IFC is superior to active controls for improving pain and disability. There is <i>limited</i> evidence that EMS is superior to passive but not active controls for improving pain, and similar to all controls for improving disability.</p><p><strong>Systematic review registration: </strong>https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=452851, Identifier (CRD42023452851).</p>","PeriodicalId":73097,"journal":{"name":"Frontiers in pain research (Lausanne, Switzerland)","volume":"5 ","pages":"1346694"},"PeriodicalIF":2.5,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11228365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-21eCollection Date: 2024-01-01DOI: 10.3389/fpain.2024.1437873
Anthony Herbert, Michael P Jankowski
{"title":"Editorial: Insight in pediatric pain - 2023.","authors":"Anthony Herbert, Michael P Jankowski","doi":"10.3389/fpain.2024.1437873","DOIUrl":"10.3389/fpain.2024.1437873","url":null,"abstract":"","PeriodicalId":73097,"journal":{"name":"Frontiers in pain research (Lausanne, Switzerland)","volume":"5 ","pages":"1437873"},"PeriodicalIF":2.5,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11224511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141556054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-19eCollection Date: 2024-01-01DOI: 10.3389/fpain.2024.1390322
Vaidehi V Paranjape, Heather K Knych, Londa J Berghaus, Shyla Giancola, Jessica Cathcart, Rachel A Reed
Background: Anatomical location-dependent differences in transdermal opioid penetration are well described in human patients. Although this has been investigated in horses with fentanyl, there is no literature available on location-dependent plasma buprenorphine concentrations when administered as a transdermal matrix-type patch.
Objective: This study aims to compare the plasma concentrations achieved from the matrix-type transdermal buprenorphine patches placed at different anatomical sites (metacarpus, gaskin, and ventral tail base) in healthy adult horses.
Study design: This is a randomized experimental study with a Latin square design.
Methods: Six adult horses were given each of three treatments with a minimum 10-day washout period. For each treatment, two 20 μg h-1 matrix-type buprenorphine patches were applied to the ventral aspect of the tail base (TailTDP), metacarpus region (MetacarpusTDP), or gaskin region (GaskinTDP). Whole blood samples (for determination of buprenorphine concentration) and physiological variables were collected before (0 h) and at 0.5, 2, 4, 6, 8, 10, 12, 16, 24, 32, 48, 56, 72, 96 and 120 h after patches were applied. The patches were removed 96 h following placement and were analyzed for residual buprenorphine content. Buprenorphine concentrations were measured in plasma by LC-MS/MS. A mixed-effects model was used to analyze the physiological variables.
Results: Between the three treatment groups, there was no change in physiological variables across timepoints as compared to baseline and when compared to each other in a single horse and between horses (p > 0.3). When comparing all three locations, the buprenorphine uptake was observed to be more consistent with respect to measurable plasma concentrations >0.1 ng ml-1 when applied to the ventral aspect of the tail base. In the TailTDP group, the mean plasma buprenorphine concentrations were >0.1 ng ml-1 from 2 to 32 h. The highest group mean was 0.25 ng ml-1 noted at 4 h.
Conclusions: The metacarpal and gaskin regions presented more erratic and inconsistent buprenorphine uptake and plasma concentrations as compared to the ventral aspect of the tail base. Further research must be directed at investigating the optimal dose, achievable duration of analgesia, change in measurable plasma concentrations, and behavioral and systemic effects.
{"title":"Plasma concentrations of buprenorphine administered via matrix-type transdermal patches applied at three different anatomical locations in healthy adult horses.","authors":"Vaidehi V Paranjape, Heather K Knych, Londa J Berghaus, Shyla Giancola, Jessica Cathcart, Rachel A Reed","doi":"10.3389/fpain.2024.1390322","DOIUrl":"10.3389/fpain.2024.1390322","url":null,"abstract":"<p><strong>Background: </strong>Anatomical location-dependent differences in transdermal opioid penetration are well described in human patients. Although this has been investigated in horses with fentanyl, there is no literature available on location-dependent plasma buprenorphine concentrations when administered as a transdermal matrix-type patch.</p><p><strong>Objective: </strong>This study aims to compare the plasma concentrations achieved from the matrix-type transdermal buprenorphine patches placed at different anatomical sites (metacarpus, gaskin, and ventral tail base) in healthy adult horses.</p><p><strong>Study design: </strong>This is a randomized experimental study with a Latin square design.</p><p><strong>Methods: </strong>Six adult horses were given each of three treatments with a minimum 10-day washout period. For each treatment, two 20 μg h<sup>-1</sup> matrix-type buprenorphine patches were applied to the ventral aspect of the tail base (Tail<sub>TDP</sub>), metacarpus region (Metacarpus<sub>TDP</sub>), or gaskin region (Gaskin<sub>TDP</sub>). Whole blood samples (for determination of buprenorphine concentration) and physiological variables were collected before (0 h) and at 0.5, 2, 4, 6, 8, 10, 12, 16, 24, 32, 48, 56, 72, 96 and 120 h after patches were applied. The patches were removed 96 h following placement and were analyzed for residual buprenorphine content. Buprenorphine concentrations were measured in plasma by LC-MS/MS. A mixed-effects model was used to analyze the physiological variables.</p><p><strong>Results: </strong>Between the three treatment groups, there was no change in physiological variables across timepoints as compared to baseline and when compared to each other in a single horse and between horses (<i>p</i> > 0.3). When comparing all three locations, the buprenorphine uptake was observed to be more consistent with respect to measurable plasma concentrations >0.1 ng ml<sup>-1</sup> when applied to the ventral aspect of the tail base. In the Tail<sub>TDP</sub> group, the mean plasma buprenorphine concentrations were >0.1 ng ml<sup>-1</sup> from 2 to 32 h. The highest group mean was 0.25 ng ml<sup>-1</sup> noted at 4 h.</p><p><strong>Conclusions: </strong>The metacarpal and gaskin regions presented more erratic and inconsistent buprenorphine uptake and plasma concentrations as compared to the ventral aspect of the tail base. Further research must be directed at investigating the optimal dose, achievable duration of analgesia, change in measurable plasma concentrations, and behavioral and systemic effects.</p>","PeriodicalId":73097,"journal":{"name":"Frontiers in pain research (Lausanne, Switzerland)","volume":"5 ","pages":"1390322"},"PeriodicalIF":2.5,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11220193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}