Painful Peripheral Neuropathy Research Articles

Neuropathic phenotypes of type 1 diabetes are related to different signatures of magnetic resonance spectroscopy-assessed brain metabolites

ObjectivesThe study aimed to investigate brain metabolites in type 1 diabetes and the associations with disease characteristics. We explored the metabolic profiles predicting different neuropathic phenotypes using multiple linear regression analyses. MethodsWe compared brain metabolites in 55 adults with type 1 diabetes (including painful diabetic peripheral neuropathy (DPN), painless DPN, without DPN) with 20 healthy controls. Proton magnetic resonance spectroscopy measurements (N-acetylaspartate (NAA), glutamate (glu), myo-inositol (mI), and glycerophosphocholine (GPC) were obtained in ratios to creatine (cre)) from the parietal region, anterior cingulate cortex and thalamus. ResultsThe overall diabetes group revealed decreased parietal NAA/cre compared to healthy controls (1.41 ± 0.12 vs. 1.55 ± 0.13,p < 0.001) and increased mI/cre (parietal: 0.62 ± 0.08 vs. 0.57 ± 0.07,p = 0.025, cingulate: 0.65 ± 0.08 vs. 0.60 ± 0.08,p = 0.033). Reduced NAA/cre was associated with more severe DPN (all p ≤ 0.04) whereas increased mI/cre was associated with higher hemoglobin A1c (HbA1c) (p = 0.02). Diabetes was predicted from decreased parietal NAA/cre, increased parietal ml/cre, and decreased thalamic glu/cre. DPN was predicted from decreased parietal NAA/cre and increased GPC/cre. Painful DPN was predicted from increased parietal GPC/cre and thalamic glu/cre. ConclusionsSpecific metabolic brain profiles were linked to the different phenotypes of diabetes, DPN and painful DPN. SignificanceAssessment of metabolic profiles could be relevant for detailed understanding of central neuropathy in diabetes.

What is the best pharmacologic treatment for painful diabetic peripheral neuropathy?

What is the best pharmacologic treatment for painful diabetic peripheral neuropathy?

Healthcare costs and medical utilization patterns associated with painful and severe painful diabetic peripheral neuropathy.

Painful diabetic peripheral neuropathy (DPN) is a common complication in patients with diabetes. It is associated with a poor quality of life and high costs of care. This study investigated the impact of painful DPN on healthcare costs and resource utilization. This was a retrospective analysis of administrative claims of adult patients with diabetes (type 1 or 2) from Optum's de-identified Clinformatics® Data Mart Database. Patients were assigned to four cohorts by presence of DPN and pain severity, based on diagnoses and prescription patterns in a one-year baseline. All-cause and diabetes-associated costs were calculated for the year following the index DPN diagnosis. Risk factors associated with presence of severely painful DPN were evaluated. Relative to those without DPN, patients who had DPN without pain, painful DPN (PDPN), or severe PDPN incurred respective increases of $3,093, $9,349, and $20,887 in average annual all-cause costs. More than half of costs from painful/severe DPN were for prescriptions and inpatient hospitalization. Severe PDPN was associated with elevated odds of diabetic amyotrophy (OR: 8.09; 95% CI: 6.84-9.56), diabetic foot ulcers (OR: 6.54, 95% CI: 6.32-6.76), and loss of mobility (OR: 2.54, 95% CI: 2.48-2.60), among other complications. Painful DPN is associated with higher healthcare costs and resource utilization, and a greater risk of debilitating conditions that limit quality of life. Future research should focus on better treatment options and more aggressive pain management strategies to reduce the negative impacts of DPN.

Genetically predicted immune cells mediate the association between gut microbiota and neuropathy pain

BackgroundPrevious observational studies have indicated a complex association between gut microbiota (GM) and neuropathic pain (NP). Nonetheless, the precise biological mechanisms underlying this association remain unclear. Therefore, we adopted a Mendelian randomization (MR) approach to investigate the causal relationship between GM and neuropathic pain including post-herpetic neuralgia (PHN), painful diabetic peripheral neuropathy (PDPN), and trigeminal neuralgia (TN), as well as to explore the potential mediation effects of immune cells.MethodsWe performed a two-step, two-sample Mendelian randomization study with an inverse variance-weighted (IVW) approach to investigate the causal role of GM on three major kinds of NP and the mediation effect of immune cells between the association of GM and NP. In addition, we determine the strongest causal associations using Bayesian weighted Mendelian randomization (BWMR) analysis. Furthermore, we will investigate the mediating role of immune cells through a two-step Mendelian randomization design.ResultsWe identified 53 taxonomies and pathways of gut microbiota that had significant causal associations with NP. In addition, we also discovered 120 immune cells that exhibited significant causal associations with NP. According to the BWMR and two-step Mendelian randomization analysis, we identified the following results CD4 on CM CD4 + (maturation stages of T cell) mediated 6.7% of the risk reduction for PHN through the pathway of fucose degradation (FUCCAT.PWY). CD28 + DN (CD4-CD8-) AC (Treg) mediated 12.5% of the risk reduction for PHN through the influence on Roseburia inulinivorans. CD45 on lymphocyte (Myeloid cell) mediated 11.9% of the risk increase for TN through the superpathway of acetyl-CoA biosynthesis (PWY.5173). HLA DR + CD8br %T cell (TBNK) mediated 3.2% of the risk reduction for TN through the superpathway of GDP-mannose-derived O-antigen building blocks biosynthesis (PWY.7323). IgD-CD38-AC (B cell) mediated 7.5% of the risk reduction for DPN through the pathway of thiazole biosynthesis I in E. coli (PWY.6892).DiscussionThese findings provided evidence supporting the causal effect of GM with NP, with immune cells playing a mediating role. These findings may inform prevention strategies and interventions directed toward NP. Future studies should explore other plausible biological mechanisms.

Effect of Multicomponent Exercise Program on Pain and Functional Mobility in Antitubercular Drug Therapy-Induced Peripheral Neuropathy in Pulmonary Tuberculosis Survivors.

Exercise therapy is a pivotal component in the multidisciplinary approach to managing tuberculosis (TB)-related peripheral neuropathy (PN). A personalized exercise protocol maximizes therapeutic benefits while minimizing the risk of symptom exacerbation. This study aimed to determine the effect of multicomponent exercise programs on pain and functional mobility in antitubercular drug therapy-induced PN in pulmonary TB survivors. In the approved experimental study, 110 participants with antitubercular study drug-induced PN were randomly assigned to two groups, and data were analyzed using IBM SPSS Statistics for Windows, Version 26 (Released 2019; IBM Corp., Armonk, New York, United States). The study's purpose was to evaluate the efficacy of a multicomponent exercise program on PN symptoms. The study assessed a multicomponent exercise regimen's effectiveness in individuals with TB-related PN. The experiment group demonstrated noteworthy pain reduction (p < 0.0001), improvement in neurological symptoms (p < 0.0001), and better functional outcomes in the 12-minute walk test (p < 0.0001) and sit-and-reach test (p < 0.0001). Conversely, the control group exhibited less significant improvements. Thelow p-values indicate the intervention's effectiveness, emphasizing its impact on pain reduction, neurological symptoms, and functional abilities in comparing the experimental and control groups. The study demonstrated the significant effectiveness of an eight-week multicomponent exercise program in individuals with pulmonary TB-related PN, showcasing notable improvements in pain reduction and functional mobility compared to a conventional single-component regimen in the control group.

Study of a painful diabetic peripheral neuropathy model induced by streptozotocin: conclusions before investigating non-paralytic botulinum molecules

Painful diabetic peripheral neuropathy (PDPN) is a common complication of diabetes characterized by peripheral nerve dysfunction and debilitating pain symptoms. This article investigates the streptozotocin (STZ)-induced model of PDPN (45 mg/kg i.p.) to evaluate whether it can be further used to study the efficacy of non-paralytic botulinum molecules in pain control. In the study changes in relative weight, glucose levels, and mechanical and temperature sensitivity in the experimental group compared to the control group of rats were assessed. The obtained data indicate the reliability of the model. The results showed a significant decrease in relative weight and alterations in glucose levels in the experimental group, highlighting the metabolic impact of PDPN. Moreover, the rats in the experimental group exhibited heightened mechanical and temperature sensitivity, mirroring the neuropathic pain experienced by patients with PDPN. These findings support the suitability of the STZ-induced PDPN model for preclinical studies investigating non-paralytic botulinum molecules as analgesics. In conclusion, this model provides a valuable platform for future research aimed at understanding the underlying mechanisms and developing effective interventions for PDPN.

Centralizing the Knowledge and Interpretation of Pain in Chemotherapy-Induced Peripheral Neuropathy: A Paradigm Shift towards Brain-Centric Approaches.

Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect of cancer treatment, often linked with pain complaints. Patients report mechanical and thermal hypersensitivity that may emerge during chemotherapy treatment and may persist after cancer remission. Whereas the latter situation disturbs the quality of life, life itself may be endangered by the appearance of CIPN during cancer treatment. The causes of CIPN have almost entirely been ascribed to the neurotoxicity of chemotherapeutic drugs in the peripheral nervous system. However, the central consequences of peripheral neuropathy are starting to be unraveled, namely in the supraspinal pain modulatory system. Based on our interests and experience in the field, we undertook a review of the brain-centered alterations that may underpin pain in CIPN. The changes in the descending pain modulation in CIPN models along with the functional and connectivity abnormalities in the brain of CIPN patients are analyzed. A translational analysis of preclinical findings about descending pain regulation during CIPN is reviewed considering the main neurochemical systems (serotoninergic and noradrenergic) targeted in CIPN management in patients, namely by antidepressants. In conclusion, this review highlights the importance of studying supraspinal areas involved in descending pain modulation to understand the pathophysiology of CIPN, which will probably allow a more personalized and effective CIPN treatment in the future.

Amitriptyline, Pregabalin and Duloxetine for Treatment of Painful Diabetic Peripheral Neuropathy.

Painful diabetic peripheral neuropathy is one of the frequent presenting complaints in diabetes and endocrine clinics. Our main objective was to compare effectiveness of three commonly prescribed drugs: amitriptyline, pregabalin and duloxetine for treatment of painful diabetic peripheral neuropathy. This was a comparative, prospective, observational study conducted among 99 diabetic patients with painful diabetic peripheral neuropathy having numeric rating pain scale ≥ 4. Thirty-three patients in each group were consecutively prescribed amitriptyline, pregabalin and duloxetine in lower dose (10mg/75mg/20mg) for first two weeks to gradually up titrate to higher dose (25mg/150mg/30mg) as per pain response for total duration of eight weeks. At the end of eight weeks, 84.9% in amitriptyline, 78.7% in pregabalin and 60.6% in duloxetine group had adequate pain reduction in form of mild or no pain. Among total patients, 42.5% patients had severe pain at baseline that decreased to 5% by the end of our study. Out of three drugs, 45.5% patients in amitriptyline group had complete resolution of pain as compared to 24.2% in pregabalin and 18.2% in duloxetine group (p value 0.05). Drowsiness (42.4%), dizziness (21.2%) and dry mouth (21.2%) were the commonest side effects among total participants in our study. Amitriptyline, pregabalin and duloxetine were all associated with adequate pain reduction among patients of painful diabetic peripheral neuropathy in our study, however, amitriptyline had more favorable findings with tolerable side effects.

Increased Thalamocortical Functional Connectivity on Discontinuation of Treatment in Painful Diabetic Peripheral Neuropathy.

Altered functional connectivity has been demonstrated in key brain regions involved in pain processing in painful diabetic peripheral neuropathy (Painful-DPN). However, the impact of neuropathic pain treatment on functional connectivity has not been investigated. Sixteen participants underwent resting state functional MRI (rs-fMRI) when optimally treated for neuropathic pain during their involvement in the OPTION-DM trial and 1-week following withdrawal of treatment. On discontinuation of pain treatment, there was a rise in functional connectivity between the left thalamus and primary somatosensory cortex (S1) and the left thalamus and insular cortex, key brain regions that are involved in cerebral processing of pain. The changes in functional connectivity between scans also correlated with measures of pain (baseline pain severity and neuropathy pain symptom inventory). Moreover, when participants were stratified into higher and lower than average baseline pain sub-groups, the change in thalamic-S1 cortical functional connectivity between scans was significantly greater in those with high baseline pain compared with the lower baseline pain group. This study shows that thalamo-cortical functional connectivity has the potential to act as an objective biomarker for neuropathic pain in diabetes for use in clinical pain trials.

Purpurin ameliorated neuropathic allodynia and hyperalgesia by modulating neuronal mitochondrial bioenergetics and redox status in type 1 diabetic mice

A substantial proportion of diabetic patients suffer a debilitating and persistent pain state, known as peripheral painful neuropathy that necessitates improved therapy or antidote. Purpurin, a natural anthraquinone compound from Rubia tinctorum L., has been reported to possess antidepressant activity in preclinical studies. As antidepressants have been typically used as standard agents against persistent neuropathic pain, this study aimed to probe the effect of purpurin on neuropathic pain associated with streptozotocin-induced type 1 diabetes in male C57BL6J mice. The Hargreaves test and the von Frey test were used to assess the pain-like behaviors, shown as heat hyperalgesia and mechanical allodynia respectively. Chronic treatment of diabetic mice with purpurin not only ameliorated the established symptoms of heat hyperalgesia and mechanical allodynia, but also arrested the development of these pain states given preemptively at low doses. Although purpurin treatment hardly impacted on metabolic disturbance in diabetic mice, it ameliorated exacerbated oxidative stress in pain-associated tissues, improved mitochondrial bioenergetics in dorsal root ganglion neurons and restored nerve conduction velocity in sciatic nerves. Notably, the analgesic actions of purpurin were modified by pharmacologically manipulating redox status and mitochondrial bioenergetics. These findings unveil the analgesic activity of purpurin, an effect that is causally associated with its bioenergetics-enhancing and antioxidant effects, in mice with type 1 diabetes.

854-P: Global, Multicenter Registry of Prospectively-Enrolled Patients Utilizing SCS for Chronic Pain—Long-Term Outcomes from a Subcohort Diagnosed with Painful Diabetic Peripheral Neuropathy

854-P: Global, Multicenter Registry of Prospectively-Enrolled Patients Utilizing SCS for Chronic Pain—Long-Term Outcomes from a Subcohort Diagnosed with Painful Diabetic Peripheral Neuropathy

1804-LB: Serum Spexin Level Is Negatively Associated with Peripheral Neuropathy and Sensory Pain in Type 2 Diabetes

1804-LB: Serum Spexin Level Is Negatively Associated with Peripheral Neuropathy and Sensory Pain in Type 2 Diabetes

Select Minor Cannabinoids from Cannabis sativa Are Cannabimimetic and Antinociceptive in a Mouse Model of Chronic Neuropathic Pain.

Chronic pain conditions affect nearly 20% of the population in the United States. Current medical interventions, such as opioid drugs, are effective at relieving pain but are accompanied by many undesirable side effects. This is one reason increased numbers of chronic pain patients have been turning to Cannabis for pain management. Cannabis contains many bioactive chemical compounds; however, current research looking into lesser-studied minor cannabinoids in Cannabis lacks uniformity between experimental groups and/or excludes female mice from investigation. This makes it challenging to draw conclusions between experiments done with different minor cannabinoid compounds between laboratories or parse out potential sex differences that could be present. We chose five minor cannabinoids found in lower quantities within Cannabis: cannabinol (CBN), cannabidivarin (CBDV), cannabigerol (CBG), Δ8-tetrahydrocannabinol (Δ8-THC), and Δ9-tetrahydrocannabivarin (THCV). These compounds were then tested for their cannabimimetic and pain-relieving behaviors in a cannabinoid tetrad assay and a chemotherapy-induced peripheral neuropathy (CIPN) pain model in male and female CD-1 mice. We found that the minor cannabinoids we tested differed in the cannabimimetic behaviors evoked, as well as the extent. We found that CBN, CBG, and high-dose Δ8-THC evoked some tetrad behaviors in both sexes, while THCV and low-dose Δ8-THC exhibited cannabimimetic tetrad behaviors only in females. Only CBN efficaciously relieved CIPN pain, which contrasts with reports from other researchers. Together these findings provide further clarity to the pharmacology of minor cannabinoids and suggest further investigation into their mechanism and therapeutic potential. SIGNIFICANCE STATEMENT: Minor cannabinoids are poorly studied ligands present in lower levels in Cannabis than cannabinoids like THC. In this study, we evaluated five minor cannabinoids (CBN, CBDV, CBG, THCV, and Δ8-THC) for their cannabimimetic and analgesic effects in mice. We found that four of the five minor cannabinoids showed cannabimimetic activity, while one was efficacious in relieving chronic neuropathic pain. This work is important in further evaluating the activity of these drugs, which are seeing wider public use with marijuana legalization.

Serum Spexin Level Is Negatively Associated With Peripheral Neuropathy and Sensory Pain in Type 2 Diabetes.

Background: Spexin is a novel peptide hormone and has shown antinociceptive effects in experimental mice. This study is aimed at evaluating the association of serum spexin level with diabetic peripheral neuropathy (DPN) and related pain in a Chinese population. Methods: We enrolled 167 type 2 diabetes mellitus (T2DM) including 56 patients without DPN (non-DPN), 67 painless DPN, and 44 painful DPN. Serum spexin was measured using ELISA. Logistic regression models were performed to analyze the independent effects of spexin on prevalence of DPN and painful DPN. In streptozotocin (STZ)-induced diabetic mice, mechanical pain threshold was measured using electronic von Frey aesthesiometer. Human peripheral blood mononuclear cells (PBMCs) were isolated and further stimulated with lipopolysaccharide without or with spexin. The gene expression was assayed by qPCR. Results: Compared with non-DPN, serum spexin level decreased in painless DPN and further decreased in painful DPN. The odds of DPN was associated with low spexin level in T2DM, which was similar by age, sex, BMI, and diabetes duration, but attenuated in smokers. The odds of having pain was associated with decreased spexin level in DPN, which was similar by age, sex, smoking status, and diabetes duration, but attenuated in normal weight. Furthermore, we observed that mechanical pain threshold increased in spexin-treated diabetic mice. We also found that lipopolysaccharide treatment increased the mRNA level of TNF-α, IL-6, and MCP-1 in human PBMCs, while spexin treatment prevented this increase. Conclusions: These results suggested that spexin might serve as a protective factor for diabetes against neuropathology and pain-related pathogenesis.

Painful diabetic peripheral neuropathy among Tunisian geriatric patients suffering from diabetes mellitus

Painful diabetic peripheral neuropathy among Tunisian geriatric patients suffering from diabetes mellitus

Terpenes from Cannabis sativa induce antinociception in a mouse model of chronic neuropathic pain via activation of adenosine A 2A receptors.

Terpenes are small hydrocarbon compounds that impart aroma and taste to many plants, including Cannabis sativa . A number of studies have shown that terpenes can produce pain relief in various pain states in both humans and animals. However, these studies were methodologically limited and few established mechanisms of action. In our previous work, we showed that the terpenes geraniol, linalool, β-pinene, α-humulene, and β-caryophyllene produced cannabimimetic behavioral effects via multiple receptor targets. We thus expanded this work to explore the potential antinociception and mechanism of these Cannabis terpenes in a mouse model of chronic pain. We first tested for antinociception by injecting terpenes (200 mg/kg, IP) into male and female CD-1 mice with mouse models of chemotherapy-induced peripheral neuropathy (CIPN) or lipopolysaccharide-induced inflammatory pain, finding that the terpenes produced roughly equal antinociception to 10 mg/kg morphine or 3.2 mg/kg WIN55,212. We further found that none of the terpenes produced reward as measured by conditioned place preference, while low doses of terpene (100 mg/kg) combined with morphine (3.2 mg/kg) produced enhanced antinociception vs either alone. We then used the adenosine A 2A receptor (A 2A R) selective antagonist istradefylline (3.2 mg/kg, IP) and spinal cord-specific CRISPR knockdown of the A 2A R to identify this receptor as the mechanism for terpene antinociception in CIPN. In vitro cAMP and binding studies and in silico modeling studies further suggested that the terpenes act as A 2A R agonists. Together these studies identify Cannabis terpenes as potential therapeutics for chronic neuropathic pain and identify a receptor mechanism for this activity.

Role of Lumbar Sympathetic MIPSI in Linezolid-induced Peripheral Neuropathy with Motor Dysfunction

Abstract Linezolid is a Class A drug of multidrug-resistant and extensively drug-resistant tuberculosis whose use carries a considerable risk of toxicity. In this study, five patients of linezolid-induced peripheral neuropathy (LIPN) showed decreased great toe power in both lower limbs (LLs). The sympathetic nervous system has been implicated in pain and motor dysfunction associated with painful peripheral neuropathy. Therapeutic interventions targeted at the sympathetic nervous system are very uncommon. We have used pain detect score (PDS) for the assessment of neuropathic pain. However, none of the criteria in the PDS questionnaire include motor response, thus in patients with sensory-motor neuropathy, we assessed great toe power, which was 4/5 in all 5 patients before lumbar sympathetic minimally invasive pain and spine intervention (MIPSI). All patients had improved pain symptoms and great toe power 5/5 immediately postprocedure, with no slipping of chappals. Here, we are providing evidence and conclude that lumbar sympathetic MIPSI is an important modality of treatment in patients with LIPN with motor dysfunction.

A Pain Physician’s Perspective on Recent Advances in Painful Diabetic Peripheral Neuropathy Management

Abstract Diabetic peripheral neuropathy (DPN) is a prevalent neurological complication linked to diabetes mellitus, exerting a substantial impact on the quality of life for those affected. This review article aims to discuss and review advances in the pain management of patients with DPN. We reviewed recent DPN management literature primarily from PubMed and SCOPUS using specific keywords, focusing on original research and recent advancements. The pathophysiology of DPN involves metabolic and vascular changes in nerve fibers, leading to direct damage and a decrease in their natural repair capacity. Effective glycemic control plays a central role in managing DPN, along with addressing other contributing factors such as comorbidities and lifestyle modifications. Nutraceuticals, including alpha-lipoic acid and Vitamin B12, have shown promising results in some studies. Antineuropathic agents such as calcium channel a2-δ ligands, serotonin and noradrenaline reuptake inhibitors, tricyclic antidepressants, and sodium channel blockers are commonly used in DPN pain management. Topical therapies, including capsaicin and lidocaine patches, have also demonstrated efficacy. Opioids are generally discouraged due to weak evidence and long-term deleterious side effects, along with the risk of addictive potential. Neuromodulation has emerged as a modality in resistant cases not responding to pharmacological management. Individualized treatment plans based on symptomatology, comorbidities, and side effect profiles should be developed for DPN patients. Comprehensive management of DPN involves a multidisciplinary approach, emphasizing patient education, regular assessment, and counseling to prevent further damage and complications.

Omega-3 Fatty Acids Prevent Peripheral Neuropathy and Pro Inflammatory Adipose Tissue Macrophage Phenotype in High-Fat-Fed Mice

Obesity and/or consumption of a high fat diet is associated with the development of peripheral neuropathy (PN) which is characterized by changes in epidermal innervation and increased sensitivity in the extremities. Evidence indicates that omega-3 fatty acids prevent the development of PN and attenuate adipose inflammation, but the interaction of PN and adipose tissue macrophage (ATMΦ) phenotype have not been investigated. We hypothesized that a diet high in unsaturated fatty acids may prevent PN and adipose inflammation, despite the high fat content. PURPOSE: Assess the effects of omega-3 fatty acids on signs of PN and ATMΦ phenotype in high-fat-fed mice. Methods: Male C57Bl/6 mice were randomized to (n = 12-14/group): 10% low fat fish oil (10% FO); 54% high fat fish oil (54% FO); 10% low fat lard (10% L); or 54% high fat lard (54% L) for 14 weeks. PN was characterized by the von Frey test for hindpaw sensitivity at baseline then biweekly through week 14. After 14 weeks, intraepidermal nerve fiber density (IENFD) was quantified by immunohistochemistry of the hindpaw footpad skin using anti-PGP 9.5. The relative percentage of total macrophage cells (F4/80+CD11b+) and M1 (CD206-CD11c+) and M2 (CD206+CD11c-) cell populations in epididymal adipose were identified using flow cytometry. Group differences were identified by 2 x 2 factorial ANOVA. Pearson correlations were used to assess the relationship between hindpaw withdrawal threshold and ATMΦ. Results: 54% L (35.3 ± 1.0 g) had greater body mass compared to all other groups: 10% FO (26.5 ± 0.7, p &lt; 0.001); 10% L (27.8 ± 0.6, p = 0.001); and 54% L (35.3 ± 1.0, p &lt; 0.001). Similarly, fasting insulin was greater in 54% L (3.1 ± 0.4 ng/mL) compared to all other groups: 10% FO (1.0 ± 1.0, p &lt; 0.001); 10% L (1.6 ± 0.2, p &lt; 0.001), and 54% FO (1.0 ± 0.1, p &lt; 0.001). Fasting glucose was greater in 54% L (225.8 ± 7.5 mg/dl) compared to 10% FO (216.1 ± 7.7, p =0.04) and 54% FO (182.6 ± 6.6, p = 0.03), but not 10% L (180.7 ± 17.1, p = 0.483). Following the same pattern as body mass and insulin, homeostatic model assessment of insulin resistance (HOMA-IR) was greater in 54% L (8.1 ± 1.1) compared to all other groups: 10% FO (2.2 ± 0.4, p &lt; 0.001); 10% L (4.1 ± 0.6, p &lt; 0.001); and 54% FO (2.2 ± 0.3, p &lt; 0.001). Hindpaw sensitivity was greater in 54% L (0.08 ± 0.02 g) compared to 54% FO (0.19 ± 0.03, p = 0.02). IENFD was greater in 54% L (52.5 ± 2.2 fibers per mm) compared to 10% FO (44.1 ± 1.5, p = 0.04), but was not different from 10% L (49.7 ± 2.8, p = 0.47) or 54% FO (48.1 ± 3.0, p = 0.24). M1 ATMΦ percentage was greater in 54% L (11.7 ± 2.5 %) compared to all other groups: 10% L (3.8 ± 0.8, p = 0.001), 10% FO (5.2 ± 0.7, p = 0.014), and 54% FO (5.1 ± 0.6 %, p = 0.016). M2 ATMΦ percentage was greater in 10% L (59.7 ± 4.5 %) compared to all other groups: 10% FO (42.1 ± 5.0, p = 0.036), 54% L (41.4 ± 3.9, p = 0.027), and 54% FO (31.4 ± 3.6 %, p &lt; 0.001), but there were no significant differences in M2 ATMΦ percentage in 54% L vs. 54% FO. There were no significant correlations between hindpaw sensitivity and M1 ATMΦ percentage, M2 ATMΦ percentage, or M1:M2 ratio. CONCLUSION: The negative metabolic effects of a high fat lard diet on body mass, glucose, insulin, and insulin resistance were prevented when the dietary fat source was omega-3 fatty acids instead of lard. Notably, mice fed a high fat lard diet had a higher percentage of the pro inflammatory M1 ATMΦ phenotype and developed signs of painful PN including hindpaw hypersensitivity and increased IENFD but these effects were prevented by omega-3 fatty acids in the 54% FO group, despite the high dietary fat content. Supported by the Southern Illinois University Edwardsville Vaughnie Lindsay New Investigator Award. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Investigating the safety and feasibility of osteopathic manipulative medicine in hospitalized children and adolescent young adults with cancer.

Children and adolescents young adults (AYAs) undergoing treatment for oncologic diagnoses are frequently hospitalized and experience unwanted therapy-induced side effects that diminish quality of life. Osteopathic manipulative treatment (OMT) is a medical intervention that utilizes manual techniques to diagnose and treat body structures. Few studies have investigated the implementation of OMT in the pediatric oncology outpatient setting. To date, no studies have investigated the safety and feasibility of OMT in the pediatric oncology inpatient setting. The objective of this study is to investigate the safety and feasibility of OMT in the pediatric oncology inpatient setting. This is a prospective, single-institution pilot study evaluating children and AYAs aged≥2 years to≤30 years with a diagnosis of cancer hospitalized at Riley Hospital for Children (RH) from September 2022 to July 2023. Approval was obtained from the Indiana University Institutional Review Board (IRB). Patients were evaluated daily with a history and physical examination as part of routine inpatient management. Patients who reported chemotherapy side effects commonly encountered and managed in the inpatient setting, such as pain, headache, neuropathy, constipation, or nausea, were offered OMT. Patients provided written informed consent/assent prior to receiving OMT. OMT was provided by trained osteopathic medical students under the supervision of a board-certified osteopathic physician and included techniques commonly taught in first- and second-year osteopathic medical school curricula. Safety was assessed by a validated pain (FACES) scale immediately pre/post-OMT and by adverse event grading per Common Terminology Criteria for Adverse Events (CTCAE) 24 h post-OMT. All data were summarized utilizing descriptive statistics. A total of 11 patients were screened for eligibility. All patients met the eligibility criteria and were enrolled in the study. The majority of patients were male (n=7, 63.6 %) with a median age of 18.2 years at time of enrollment (range, 10.2-29.8 years). Patients had a variety of hematologic malignancies including B-cell acute lymphoblastic leukemia (ALL) (n=5, 45.5 %), T-cell ALL (n=1, 9.1 %), acute myeloid leukemia (AML) (n=2, 18.2 %), non-Hodgkin's lymphoma (n=2, 18.2 %), and Hodgkin's lymphoma (n=1, 9.1 %). All patients were actively undergoing cancer-directed therapy at the time of enrollment. There were 40 unique reasons for OMT reported and treated across 37 encounters, including musculoskeletal pain (n=23, 57.5 %), edema (n=7, 17.5 %), headache (n=5, 12.5 %), peripheral neuropathy (n=2, 5.0 %), constipation (n=2, 5.0 %), and epigastric pain not otherwise specified (n=1, 2.5 %). Validated FACES pain scores were reported in 27 encounters. Of the 10 encounters for which FACES pain scores were not reported, 8 encounters addressed lower extremity edema, 1 encounter addressed peripheral neuropathy, and 1 encounter addressed constipation. The total time of OMT was documented for 33 of the 37 encounters and averaged 9.8 min (range, 3-20 min). Hospitalized children and AYAs with cancer received OMT safely with decreased pain in their reported somatic dysfunction(s). These findings support further investigation into the safety, feasibility, and efficacy of implementing OMT in the pediatric oncology inpatient setting and to a broader inpatient pediatric oncology population.