Ignite Creation Date:
2024-05-06 @ 10:45 AM
Last Modification Date:
2024-10-26 @ 12:35 PM
Study NCT ID:
NCT03344913
Status:
COMPLETED
Last Update Posted:
2022-09-07
First Post:
2017-11-08
Brief Title:
Biologic Mechanisms for Pain Variation After Physical Activity in Osteoarthritis
Sponsor:
University of Maryland Baltimore
Organization:
University of Maryland Baltimore
Study Overview
Official Title:
Bioenergetics Inflammation and Protein Expression as Mechanisms for Variation in Pain Sensitivity After Physical Activity in Adults With Knee Osteoarthritis
Status:
COMPLETED
Status Verified Date:
2022-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Osteoarthritis OA in the knee is characterized by chronic inflammatory pain that is not necessarily related to the amount of joint damage Clinical practice guidelines recommend physical activity PA for osteoarthritis pain but most adults with OA do not engage in PA One reason for this is that while PA can reduce OA related joint pain it does not work for everyone PA decreases pain sensitivity for about half of adults with OA but increases pain sensitivity for the other half The investigators are hypothesizing that individual differences in how well cells work to make energy inflammation and different proteins available in blood cells explains who PA will work to reduce pain and who it wont among adults with OA The purpose of this pilot study is to determine if blood cells ability to make cellular energy inflammation and proteins help explain the difference about who PA reduces activity for and who it doesnt The investigators will compare these biologic factors and pain sensitivity before walking immediately after 30 minutes of walking ie acute and after six weeks of walking three times a week for 30 minutes ie long-term in adults with hip or knee osteoarthritis The investigators will also compare these results to adults without OA The investigators will recruit a sample of 40 adults with radiologic eg x-ray or CT scan evidence of hip or knee OA and 20 agegender matched healthy adults without OA to address the following study aims Aim 1 To examine the effects of a six week three daysweek walking program on pain in adults with OA as compared to healthy controls Aim 2 To test the cells ability to make energy as a mechanism for variation in pain after acute and long-term PA in older adults with lower extremity osteoarthritis Aim3 To test the role of inflammation as a mechanism for variation in pain after acute and long-term physical activity in adults with lower extremity osteoarthritis Aim 4 To generate hypotheses regarding the role of proteomics in variation in pain after acute and long-term physical activity
Detailed Description:
Osteoarthritis OA in the knee is characterized by chronic inflammatory pain that is not necessarily associated with the amount of joint damage1 Clinical practice guidelines recommend physical activity PA for osteoarthritis pain2 but uptake of PA among adults with OA is very low3 One reason for this is that while PA can reduce pain among adults with lower extremity OA45 it does so differentially decreasing pain sensitivity for about half of adults with OA but actually increasing pain sensitivity for the other half6 Further a recent meta-analysis revealed that engaging in a single type of PA eg aerobic exercise or resistance training reduces OA knee pain but there was large heterogeneity in the results which could not be explained by age sex BMI alignment in the knee disease severity or baseline pain5 One of the goals of developing individualized PA interventions for adults with OA is to elucidate the mechanisms by which PA reduces OA pain and for whom PA most effectively diminishes the pain
Aerobic physical activity such as walking increases cellular capacity for energy generation ATP production via oxidative phosphorylation up to 2-fold by stimulating mitochondrial biogenesis78 This phenomenon occurs not only in skeletal muscle7 but also in brain cells910 liver cells91112 adipose tissue13 kidney cells12 and leukocytes14 indicating that PA likely increases metabolic demand systemically Moreover PA is thought to create adaptive changes in the activity andor abundance of proteins involved in processes related to mitochondrial function8 Mitochondrial function including energy generation through oxidative phosphorylation inflammation and mitochondrial related protein expression are key features in osteoarthritis1516 and chronic inflammatory pain1718 Animal models of inflammatory pain demonstrate a cellular metabolic shift from oxidative phosphorylation to glycolysis in chronic inflammatory states via the pyruvate dehydrogenase kinase 24 PKD24-pyruvate dehydrogenase PDH-lactic acid axis19 This results in an increase in lactic acid production in the affected area The ensuing acidic microenvironment amplifies the nociceptive response via recruitment of additional pro-algesic proinflammatory cytokines which activate nociceptors and spinal glia to cause peripheral and central sensitizations respectively19 Thus improvement in the capacity to generate ATP through oxidative phosphorylation and associated reduction of glycolysis may reduce pain sensitivity However while a large body of animal and correlational data supports a strong link between oxidative potential and pain outcomes experimental evidence of cause and effect remains sparse especially in humans8
The investigators are hypothesizing that individual differences in systemic cellular bioenergetic function inflammation and protein expression influence the effect of PA to reduce pain sensitivity in adults with knee OA The purpose of this quasi-experimental pilot study is to test mitochondrial bioenergetics oxidative phosphorylation mitochondrial content in platelets inflammation cytokines and protein expression as mechanisms for variation in pain sensitivity immediately after 30 minutes of walking ie acute and after six weeks of walking three times a week for 30 minutes ie long-term in adults with knee osteoarthritis The investigators will address the following specific aims and hypotheses in a sample of 40 adults with radiologic evidence of hip or knee OA and 20 agegender matched healthy controls
Aim 1 To examine the effects of a six week three daysweek walking program on pain thresholds in adults with knee OA as compared to healthy controls H11 Pain sensitivity Quantitative Sensory Testing will increase in approximately 50 of adults with OA and decrease in approximately 50 of adults with OA after acute and long-term PA
H12 Pain sensitivity will decrease in healthy controls after acute and long-term PA
Aim2 To test the role of mitochondrial bioenergetics oxidative phosphorylation mitochondrial content as a mechanism for variation in pain sensitivity after PA in older adults with knee OA
H21 Pain sensitivity is negatively associated with mitochondrial function oxidative phosphorylation mitochondrial content in platelets at baseline after acute PA and long-term PA H22 Healthy controls will have higher capacity for oxidative phosphorylation in platelets than OA participants
Aim3 To test the role of inflammation as a mechanism for variation in pain sensitivity after physical activity in older adults with knee OA
H31 Pain sensitivity is positively associated with increased circulating proinflammatory cytokines c-reactive protein interleukin IL-1 IL-1β IL-6 IL-10 tumor necrosis factor TNF-α PGES at baseline after acute and long-term PA
Aim 4 To generate hypotheses regarding the role of proteomics in variation in pain sensitivity after physical activity immediacy following and after six weeks of walking program Changes in protein expression will depend on the half-life of the protein being expressed which can range from minutes to days8 Thus it is important to examine adaptive changes in protein expression in both the short minutesday post PA and long term daysweeks between bouts of physical activity
Aerobic physical activity such as walking increases cellular capacity for energy generation ATP production via oxidative phosphorylation up to 2-fold by stimulating mitochondrial biogenesis78 This phenomenon occurs not only in skeletal muscle7 but also in brain cells910 liver cells91112 adipose tissue13 kidney cells12 and leukocytes14 indicating that PA likely increases metabolic demand systemically Moreover PA is thought to create adaptive changes in the activity andor abundance of proteins involved in processes related to mitochondrial function8 Mitochondrial function including energy generation through oxidative phosphorylation inflammation and mitochondrial related protein expression are key features in osteoarthritis1516 and chronic inflammatory pain1718 Animal models of inflammatory pain demonstrate a cellular metabolic shift from oxidative phosphorylation to glycolysis in chronic inflammatory states via the pyruvate dehydrogenase kinase 24 PKD24-pyruvate dehydrogenase PDH-lactic acid axis19 This results in an increase in lactic acid production in the affected area The ensuing acidic microenvironment amplifies the nociceptive response via recruitment of additional pro-algesic proinflammatory cytokines which activate nociceptors and spinal glia to cause peripheral and central sensitizations respectively19 Thus improvement in the capacity to generate ATP through oxidative phosphorylation and associated reduction of glycolysis may reduce pain sensitivity However while a large body of animal and correlational data supports a strong link between oxidative potential and pain outcomes experimental evidence of cause and effect remains sparse especially in humans8
The investigators are hypothesizing that individual differences in systemic cellular bioenergetic function inflammation and protein expression influence the effect of PA to reduce pain sensitivity in adults with knee OA The purpose of this quasi-experimental pilot study is to test mitochondrial bioenergetics oxidative phosphorylation mitochondrial content in platelets inflammation cytokines and protein expression as mechanisms for variation in pain sensitivity immediately after 30 minutes of walking ie acute and after six weeks of walking three times a week for 30 minutes ie long-term in adults with knee osteoarthritis The investigators will address the following specific aims and hypotheses in a sample of 40 adults with radiologic evidence of hip or knee OA and 20 agegender matched healthy controls
Aim 1 To examine the effects of a six week three daysweek walking program on pain thresholds in adults with knee OA as compared to healthy controls H11 Pain sensitivity Quantitative Sensory Testing will increase in approximately 50 of adults with OA and decrease in approximately 50 of adults with OA after acute and long-term PA
H12 Pain sensitivity will decrease in healthy controls after acute and long-term PA
Aim2 To test the role of mitochondrial bioenergetics oxidative phosphorylation mitochondrial content as a mechanism for variation in pain sensitivity after PA in older adults with knee OA
H21 Pain sensitivity is negatively associated with mitochondrial function oxidative phosphorylation mitochondrial content in platelets at baseline after acute PA and long-term PA H22 Healthy controls will have higher capacity for oxidative phosphorylation in platelets than OA participants
Aim3 To test the role of inflammation as a mechanism for variation in pain sensitivity after physical activity in older adults with knee OA
H31 Pain sensitivity is positively associated with increased circulating proinflammatory cytokines c-reactive protein interleukin IL-1 IL-1β IL-6 IL-10 tumor necrosis factor TNF-α PGES at baseline after acute and long-term PA
Aim 4 To generate hypotheses regarding the role of proteomics in variation in pain sensitivity after physical activity immediacy following and after six weeks of walking program Changes in protein expression will depend on the half-life of the protein being expressed which can range from minutes to days8 Thus it is important to examine adaptive changes in protein expression in both the short minutesday post PA and long term daysweeks between bouts of physical activity
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 1P30NR016579-01 | NIH | None | httpsreporternihgovquickSearch1P30NR016579-01 |