Frontiers in Pain Research最新文献

{"title":"Parental knowledge and attitude of postoperative paediatric pain: stepwise linear regression analysis","authors":"Mitiku Desalegn, Tewoderos Shitemaw, Genanew Kassie Getahun, Lire Lemma","doi":"10.3389/fpain.2024.1340375","DOIUrl":"https://doi.org/10.3389/fpain.2024.1340375","url":null,"abstract":"Despite the fact that mothers care for their children's pain in most cases, it has been noted that mothers have limited knowledge and attitude about paediatric pain. This study aims to assess parental knowledge and attitude of postoperative paediatric pain (POPP).This is institutional based cross sectional study conducted with 102 parents at Nigist Eleni Mohamed Memorial Comprehensive Specialized Hospital (NEMMCSH). A convenience sampling technique was used to select parents. This study has used a questionnaire (Parental Pain Expression Perception (PPEM), examine parents' attitudes and knowledge about how their children exhibit their pain and Medication Attitude Questioner (MAQs), focuses on how parents feel about giving their child analgesic medication to alleviate post-operative pain). Descriptive statistics were utilized to analyse the parent's response and presented with frequency and percentage. Factor analysis to analyze factor structure and stepwise linear regression analysis to examine the impact of socio-demographic factors in predicting parental knowledge and attitude about POPP were done. The statistical tests were performed at 95% confidence interval and 5% significance level.A total of 102 parents fulfilling the inclusion criteria were included. About 78% of parents agreed that children always express pain by crying or whining. The majority of parents (75.6%) believe children who are playing are not in pain. Regarding parental attitudes about pain medications, majority of parents (61%) believe that children should be given pain medication as little as possible because of its side effects. According to about 26.8% of parents, giving children pain medication for pain might teach them to use drugs for other issues. On the other hand, 63.4% of parents say that giving children pain medication as little as possible is the most effective way to manage their pain. Parents of younger children and parents from rural area are more likely to score higher in attention seeking sub-score of PPEP while parents from urban residence and those parents who are employed are more likely to perceive about the side effects of pain medications (Side effects factors).The overall knowledge and attitude of parents about postoperative pain and pain medications were poor.","PeriodicalId":12641,"journal":{"name":"Frontiers in Pain Research","volume":"6 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140230502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pain relief and associated factors: a cross-sectional observational web-based study in a Quebec cohort of persons living with chronic pain","authors":"Meriem Zerriouh, Gwenaëlle De Clifford-Faugère, Hermine Lore Nguena Nguefack, M. G. Pagé, Line Guénette, Lucie Blais, A. Lacasse","doi":"10.3389/fpain.2024.1306479","DOIUrl":"https://doi.org/10.3389/fpain.2024.1306479","url":null,"abstract":"Randomized clinical trials are used to evaluate the efficacy of various pain treatments individually, while a limited number of observational studies have portrayed the overall relief experienced by persons living with chronic pain. This study aimed to describe pain relief in real-world clinical settings and to identify associated factors.This exploratory web-based cross-sectional study used data from 1,419 persons recruited in the community. Overall pain relief brought by treatments used by participants was assessed using a 0%–100% scale (10-unit increments).A total of 18.2% of participants reported minimal pain relief (0%–20%), 60.0% moderate to substantial pain relief (30%–60%), and 21.8% extensive pain relief (70%–100%). Multivariable multinomial regression analysis revealed factors significantly associated with greater pain relief, including reporting a stressful event as circumstances surrounding the onset of pain, living with pain for ≥10 years, milder pain intensity, less catastrophic thinking, use of prescribed pain medications, use of nonpharmacological pain treatments, access to a trusted healthcare professional, higher general health scores, and polypharmacy. Factors associated with lower pain relief included surgery as circumstances surrounding pain onset, use of over-the-counter pain medications, and severe psychological distress.In this community sample of persons living with chronic pain, 8 out of 10 persons reported experiencing at least moderate relief with their treatment. The analysis has enabled us to explore potential modifiable factors as opportunities for improving the well-being of persons living with chronic pain.","PeriodicalId":12641,"journal":{"name":"Frontiers in Pain Research","volume":"45 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140238588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of physical variables, thermal nociceptive threshold testing and pharmacokinetics during placement of transdermal buprenorphine matrix-type patch in healthy adult horses","authors":"V. Paranjape, Heather K. Knych, L. Berghaus, Jessica Cathcart, S. Giancola, Hannah Craig, Caroline James, Siddharth Saksena, Rachel A. Reed","doi":"10.3389/fpain.2024.1373555","DOIUrl":"https://doi.org/10.3389/fpain.2024.1373555","url":null,"abstract":"Matrix type transdermal buprenorphine patches have not been investigated in horses and may provide an effective means of providing continuous pain control for extended period and eliminating venous catheterization.Assessment of the physiological variables (heart rate, respiratory rate, body temperature) and thermal nociceptive threshold testing, and describing the pharmacokinetic profile of transdermal buprenorphine matrix-type patch (20 μg h−1 and 40 μg h−1 dosing) in healthy adult horses.Randomised experimental study with a Latin-square design.Six adult healthy horses received each of the three treatments with a minimum 10 day washout period. BUP0 horses did not receive a patch (control). BUP20 horses received one patch (20 μg h−1) applied on the ventral aspect of the tail base resulting in a dose of 0.03–0.04 μg kg−1 h−1. BUP40 horses received two patches placed alongside each other (40 μg h−1) on the tail base resulting in a dose of 0.07–0.09 μg kg−1 h−1. Whole blood samples (for determination of buprenorphine concentration), physiological variables and thermal threshold testing were performed before (0 h) and at 2, 4, 8, 12, 16, 24, 32, 40, 48, 56, 64, 72, and 96 h after patch application. The patches were removed 72 h following placement and were analyzed for residual buprenorphine content.Between the three groups, there was no change in physiological variables across timepoints as compared to baseline (p > 0.1). With the higher dose, there was a significant increase in thermal thresholds from baseline values from 2 h until 48 h and these values were significantly higher than the group receiving the lower patch dose for multiple timepoints up to 40 h. 40 μg h−1 patch led to consistent measurable plasma concentrations starting at 2 h up to 96 h, with the mean plasma concentrations of > 0.1 ng/ml from 4 h to 40 h.20 μg h−1 and 40 μg h−1 patch doses were well tolerated by all horses. At higher dose, plasma buprenorphine concentrations were more consistently measurable and blunted thermal thresholds for 48 h vs. 32 h with 20 μg h−1 dosing as compared to control.","PeriodicalId":12641,"journal":{"name":"Frontiers in Pain Research","volume":"81 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140251881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cluster headache: an update on clinical features, epidemiology, pathophysiology, diagnosis, and treatment","authors":"Daniel San-Juan, Karina Velez-Jimenez, Jan Hoffmann, A. Martínez-Mayorga, Agustín Melo-Carrillo, Ildefonso Rodriguez-Leyva, Silvia García, M. A. Collado-Ortiz, Erwin Chiquete, Manuel Gudiño-Castelazo, Humberto Juárez-Jimenez, Marco Martínez-Gurrola, Alejandro Marfil, Juan Alberto Nader-Kawachi, Paul David Uribe-Jaimes, Rubén Darío-Vargas, Jorge Villareal-Careaga","doi":"10.3389/fpain.2024.1373528","DOIUrl":"https://doi.org/10.3389/fpain.2024.1373528","url":null,"abstract":"Cluster headache (CH) is one of the worst primary headaches that remain underdiagnosed and inappropriately treated. There are recent advances in the understanding of this disease and available treatments. This paper aims to review CH's recent clinical and pathophysiological findings, diagnosis, and treatment. We performed a narrative literature review on the socio-demographics, clinical presentations, pathophysiological findings, and diagnosis and treatment of CH. CH affects 0.1% of the population with an incidence of 2.07–9.8/100,00 person-years-habitants, a mean prevalence of 53/100,000 inhabitants (3–150/100,000 inhabitants). The male-to-female ratio remains inconclusive, as the ratio of 4.3:1 has recently been modified to 1.3–2.6, possibly due to previous misdiagnosis in women. Episodic presentation is the most frequent (80%). It is a polygenetic and multifactorial entity that involves dysfunction of the trigeminovascular system, the trigeminal autonomic reflex, and the hypothalamic networks. An MRI of the brain is mandatory to exclude secondary etiologies. There are effective and safe pharmacological treatments oxygen, sphenopalatine, and great occipital nerve block, with the heterogeneity of clinical trial designs for patients with CH divided into acute, transitional, or bridge treatment (prednisone) and preventive interventions. In conclusion, CH remains underdiagnosed, mainly due to a lack of awareness within the medical community, frequently causing a long delay in reaching a final diagnosis. Recent advances in understanding the principal risk factors and underlying pathophysiology exist. There are new therapeutic possibilities that are effective for CH. Indeed, a better understanding of this challenging pathology will continue to be a subject of research, study, and discoveries in its diagnostic and therapeutic approach.","PeriodicalId":12641,"journal":{"name":"Frontiers in Pain Research","volume":"50 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140076784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of opioid administration on the incidence of postanaesthetic colic in horses","authors":"Rhea Haralambus, Michaela Juri, Anna Mokry, Florien Jenner","doi":"10.3389/fpain.2024.1347548","DOIUrl":"https://doi.org/10.3389/fpain.2024.1347548","url":null,"abstract":"Effective management of postoperative pain is essential to ensure patient welfare, reduce morbidity and optimize recovery. Opioids are effective in managing moderate to severe pain in horses but concerns over their adverse effects on gastrointestinal (GI) motility and associated increased colic risk limit their widespread use. Studies investigating the impact of systemic opioids on both GI motility and colic incidence in horses have yielded inconclusive outcomes. Therefore, this retrospective study aims to assess the influence of systemic administration of butorphanol, morphine, and methadone on post-anaesthetic colic (PAC) incidence. Horses undergoing general anaesthesia for non-gastrointestinal procedures that were hospitalized for at least 72 h post-anaesthesia were included in this study. Anaesthetised horses were stratified by procedure type into horses undergoing diagnostic imaging without surgical intervention, emergency or elective surgery. In addition, patients were grouped by opioid treatment regime into horses receiving no opioids, intraanaesthetic, short- (<24 h) or long-term (>24 h) postoperative opioids. Administered opioids encompassed butorphanol, morphine and methadone. The number of horses showing signs of colic in the 72 h after anaesthesia was assessed for each group. A total of 782 horses were included, comprising 659 undergoing surgical procedures and 123 undergoing diagnostic imaging. The overall PAC incidence was 15.1%. Notably, horses undergoing diagnostic imaging without surgery had a significantly lower PAC rate of 6.5% compared to those undergoing surgery (16.7%, p = 0.0146). Emergency surgeries had a significantly lower PAC rate of 5.8% compared to elective procedures (18%, p = 0.0113). Of the 782 horses, 740 received intraoperative opioids and 204 postoperative opioids, 102 of which long-term (≥24 h). Neither intraoperative (p = 0.4243) nor short-term postoperative opioids (p = 0.5744) increased PAC rates. Notably, only the long-term (≥24 h) administration of morphine significantly increased PAC incidence to 34% (p = 0.0038). In contrast, long-term butorphanol (5.3% PAC, p = 0.8482) and methadone (18.4% PAC, p = 0.6161) did not affect PAC rates. In summary, extended morphine administration was the only opioid treatment associated with a significantly increased risk of PAC.","PeriodicalId":12641,"journal":{"name":"Frontiers in Pain Research","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139958533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarkers for assessing pain and pain relief in the neonatal intensive care unit","authors":"Judith A. ten Barge, Mathilde Baudat, N. Meesters, A. Kindt, E. Joosten, I. K. Reiss, S. Simons, G. van den Bosch","doi":"10.3389/fpain.2024.1343551","DOIUrl":"https://doi.org/10.3389/fpain.2024.1343551","url":null,"abstract":"Newborns admitted to the neonatal intensive care unit (NICU) regularly undergo painful procedures and may face various painful conditions such as postoperative pain. Optimal management of pain in these vulnerable preterm and term born neonates is crucial to ensure their comfort and prevent negative consequences of neonatal pain. This entails accurate and timely identification of pain, non-pharmacological pain treatment and if needed administration of analgesic therapy, evaluation of treatment effectiveness, and monitoring of adverse effects. Despite the widely recognized importance of pain management, pain assessment in neonates has thus far proven to be a challenge. As self-report, the gold standard for pain assessment, is not possible in neonates, other methods are needed. Several observational pain scales have been developed, but these often rely on snapshot and largely subjective observations and may fail to capture pain in certain conditions. Incorporation of biomarkers alongside observational pain scores holds promise in enhancing pain assessment and, by extension, optimizing pain treatment and neonatal outcomes. This review explores the possibilities of integrating biomarkers in pain assessment in the NICU.","PeriodicalId":12641,"journal":{"name":"Frontiers in Pain Research","volume":"51 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139775480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarkers for assessing pain and pain relief in the neonatal intensive care unit","authors":"Judith A. ten Barge, Mathilde Baudat, N. Meesters, A. Kindt, E. Joosten, I. K. Reiss, S. Simons, G. van den Bosch","doi":"10.3389/fpain.2024.1343551","DOIUrl":"https://doi.org/10.3389/fpain.2024.1343551","url":null,"abstract":"Newborns admitted to the neonatal intensive care unit (NICU) regularly undergo painful procedures and may face various painful conditions such as postoperative pain. Optimal management of pain in these vulnerable preterm and term born neonates is crucial to ensure their comfort and prevent negative consequences of neonatal pain. This entails accurate and timely identification of pain, non-pharmacological pain treatment and if needed administration of analgesic therapy, evaluation of treatment effectiveness, and monitoring of adverse effects. Despite the widely recognized importance of pain management, pain assessment in neonates has thus far proven to be a challenge. As self-report, the gold standard for pain assessment, is not possible in neonates, other methods are needed. Several observational pain scales have been developed, but these often rely on snapshot and largely subjective observations and may fail to capture pain in certain conditions. Incorporation of biomarkers alongside observational pain scores holds promise in enhancing pain assessment and, by extension, optimizing pain treatment and neonatal outcomes. This review explores the possibilities of integrating biomarkers in pain assessment in the NICU.","PeriodicalId":12641,"journal":{"name":"Frontiers in Pain Research","volume":"320 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139835118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Could sex-specific subtypes of hand osteoarthritis exist? A retrospective study in women presenting to secondary care","authors":"Malvika Gulati, Gretchen Brewer, Andrew Judge, Donna Kennedy, Tonia L. Vincent, Fiona E. Watt","doi":"10.3389/fpain.2024.1331187","DOIUrl":"https://doi.org/10.3389/fpain.2024.1331187","url":null,"abstract":"Hand osteoarthritis is more common in women, and its risk increases around the time of the menopause. We set out to describe the timing between menopause and the onset of symptomatic hand osteoarthritis (OA), and associations with the use of hormone replacement therapy (HRT) or its discontinuation, describing any identifiable subgroups of women.Retrospective healthcare-records study of sequential women referred to a specialist hand OA clinic, 2007–2015. Confirmation of hand OA diagnosis was by clinican, by accepted criteria. Demographics and clinical variables were from healthcare-records, recorded by standardised proforma. Outcomes of interest were reported age of onset of hand symptoms, reported age at final menstrual period (FMP), time from FMP to reported onset of hand symptoms and time from cessation of HRT to reported onset of hand symptoms. Exposure categories for systemic HRT use were never users, current users, previous users. Analysis of Variance compared groups; linear regression analysed associations of exposure with outcome.82/92(89%) of eligible women were post-menopausal, mean age at FMP 49.9 years (SD5.4). In these post-menopausal women, median time from FMP to hand symptom onset was 3 years. 48/82 (59%) developed hand symptoms within the defined peri-menopausal period (FMP ± 4 years), whilst some women developed their symptoms before or after (range −25, 30 years). In women who discontinued HRT prior to symptom onset, the median time from HRT cessation to onset of hand symptoms was 6 months. Past HRT users were older at hand symptom onset than women who had not taken HRT [coeff.4.7 years (0.92, 8.39); P = 0.015].This study adds to evidence associating the menopause/sex hormone deficiency with hand OA symptom onset in a sizeable subgroup of women (but not all). HRT use/cessation appears to influence the timing of onset of hand OA symptoms. It is not possible to interpret from this type of study whether sex hormone deficiency is causative of disease or modulates its symptoms. It is also not possible to judge whether painful hand osteoarthritis in post-menopausal women is a subtype of disease. Further investigation is indicated of sex-specific subtypes and potential for personalised medicine for post-menopausal women with hand osteoarthritis, as a clearly definable high-risk subgroup.","PeriodicalId":12641,"journal":{"name":"Frontiers in Pain Research","volume":"37 25","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139782510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Could sex-specific subtypes of hand osteoarthritis exist? A retrospective study in women presenting to secondary care","authors":"Malvika Gulati, Gretchen Brewer, Andrew Judge, Donna Kennedy, Tonia L. Vincent, Fiona E. Watt","doi":"10.3389/fpain.2024.1331187","DOIUrl":"https://doi.org/10.3389/fpain.2024.1331187","url":null,"abstract":"Hand osteoarthritis is more common in women, and its risk increases around the time of the menopause. We set out to describe the timing between menopause and the onset of symptomatic hand osteoarthritis (OA), and associations with the use of hormone replacement therapy (HRT) or its discontinuation, describing any identifiable subgroups of women.Retrospective healthcare-records study of sequential women referred to a specialist hand OA clinic, 2007–2015. Confirmation of hand OA diagnosis was by clinican, by accepted criteria. Demographics and clinical variables were from healthcare-records, recorded by standardised proforma. Outcomes of interest were reported age of onset of hand symptoms, reported age at final menstrual period (FMP), time from FMP to reported onset of hand symptoms and time from cessation of HRT to reported onset of hand symptoms. Exposure categories for systemic HRT use were never users, current users, previous users. Analysis of Variance compared groups; linear regression analysed associations of exposure with outcome.82/92(89%) of eligible women were post-menopausal, mean age at FMP 49.9 years (SD5.4). In these post-menopausal women, median time from FMP to hand symptom onset was 3 years. 48/82 (59%) developed hand symptoms within the defined peri-menopausal period (FMP ± 4 years), whilst some women developed their symptoms before or after (range −25, 30 years). In women who discontinued HRT prior to symptom onset, the median time from HRT cessation to onset of hand symptoms was 6 months. Past HRT users were older at hand symptom onset than women who had not taken HRT [coeff.4.7 years (0.92, 8.39); P = 0.015].This study adds to evidence associating the menopause/sex hormone deficiency with hand OA symptom onset in a sizeable subgroup of women (but not all). HRT use/cessation appears to influence the timing of onset of hand OA symptoms. It is not possible to interpret from this type of study whether sex hormone deficiency is causative of disease or modulates its symptoms. It is also not possible to judge whether painful hand osteoarthritis in post-menopausal women is a subtype of disease. Further investigation is indicated of sex-specific subtypes and potential for personalised medicine for post-menopausal women with hand osteoarthritis, as a clearly definable high-risk subgroup.","PeriodicalId":12641,"journal":{"name":"Frontiers in Pain Research","volume":"82 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139842365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adeno-associated virus-mediated gene transfer of arginine decarboxylase to the central nervous system prevents opioid analgesic tolerance","authors":"C. Churchill, Cristina D. Peterson, K. Kitto, Kelsey R. Pflepsen, L. Belur, R. McIvor, L. Vulchanova, George L. Wilcox, C. Fairbanks","doi":"10.3389/fpain.2023.1269017","DOIUrl":"https://doi.org/10.3389/fpain.2023.1269017","url":null,"abstract":"Agmatine, a decarboxylated form of L-arginine, prevents opioid analgesic tolerance, dependence, and self-administration when given by both central and systemic routes of administration. Endogenous agmatine has been previously detected in the central nervous system. The presence of a biochemical pathway for agmatine synthesis offers the opportunity for site-specific overexpression of the presumptive synthetic enzyme for local therapeutic effects. In the present study, we evaluated the development of opioid analgesic tolerance in ICR-CD1 mice pre-treated with either vehicle control or intrathecally delivered adeno-associated viral vectors (AAV) carrying the gene for human arginine decarboxylase (hADC). Vehicle-treated or AAV-hADC-treated mice were each further divided into two groups which received repeated delivery over three days of either saline or systemically-delivered morphine intended to induce opioid analgesic tolerance. Morphine analgesic dose-response curves were constructed in all subjects on day four using the warm water tail flick assay as the dependent measure. We observed that pre-treatment with AAV-hADC prevented the development of analgesic tolerance to morphine. Peripheral and central nervous system tissues were collected and analyzed for presence of hADC mRNA. In a similar experiment, AAV-hADC pre-treatment prevented the development of analgesic tolerance to a high dose of the opioid neuropeptide endomorphin-2. Intrathecal delivery of anti-agmatine IgG (but not normal IgG) reversed the inhibition of endomorphin-2 analgesic tolerance in AAV-hADC-treated mice. To summarize, we report here the effects of AAV-mediated gene transfer of human ADC (hADC) in models of opioid-induced analgesic tolerance. This study suggests that gene therapy may contribute to reducing opioid analgesic tolerance.","PeriodicalId":12641,"journal":{"name":"Frontiers in Pain Research","volume":" 20","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139788472","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}