{"id":{"repo_id":"loyola-thes","oai_identifier":"oai:ecommons.luc.edu:luc_diss-1186"},"canonical_url":"https://search.dev.ndltd.org/etd/loyola-thes/oai:ecommons.luc.edu:luc_diss-1186","repository":{"repo_id":"loyola-thes","name":"Loyola University Chicago","base_url":"https://ecommons.luc.edu/do/oai/"},"display":{"title":"Forced-Exercise Alleviates Neuropathic Pain in Experimental Diabetes: Effects on Voltage-Gated Calcium Channels","abstract":"

Exercise is now established as an integral adjunct to the management of diabetes. Diabetic polyneuropathy, a painful complication of diabetes, remains untreatable, emphasizing a critical need for improved therapeutic strategies. Recent evidence suggests that exercise may facilitate recovery of peripheral nerve function in diabetes. However, the mechanism by which exercise protects against diabetes-induced nerve dysfunction is unknown. In this dissertation we hypothesized that forced-exercise protects against experimental DPN by preventing glucose-associated alterations of voltage-gated calcium currents (VGCC) in small diameter dorsal root ganglion (DRG) neurons. Using behavioral, nerve-electrophysiology and patch-clamp methodology we examined the functional consequences of forced-exercise (treadmill, 5.4 km/week) on VGCC in dissociated small diameter DRG neurons from rats conferred diabetic by streptozotocin (STZ) treatment. Exercised-STZ rats in comparison to sedentary-STZ rats, demonstrated a 4 week delay in the onset of tactile hyperalgesia that was independent of changes in blood glucose levels. Interestingly, forced-exercise induced protection against diabetes-induced tactile hyperalgesia was reversed in a dose dependent manner by the opioid antagonist, naloxone. Forced-Exercise also prevented peripheral nerve conduction deficits in STZ-treated rats. Small diameter DRG neurons harvested from sedentary-STZ rats with demonstrated hyperalgesia exhibited 2-fold increase in peak high-voltage activated (HVA) Ca2+ current density and low-voltage activated (LVA) Ca2+ current component. The steady-state inactivation (SSI) (measure of channel availability) of LVA currents demonstrated a rightward shift in sedentary-STZ rats (+7.5 mV shift; V50 = -50.9 ± 0.6 mV; vehicle treated rats V50 = -58.4 ± 0.9 mV). Forced-exercise prevented the increase in both, peak HVA Ca2+ current density and LVA SSI shift (V50 = -58.2 ± 1.4 mV), but did not alter LVA current component. We conclude that forced-exercise delayed the onset of diabetic tactile hyperalgesia by preventing the alteration of VGCCs in small diameter DRG neurons, possibly by decreasing total calcium influx and dampening neuronal over-excitability.

","abstract_html":"<p>Exercise is now established as an integral adjunct to the management of diabetes. Diabetic polyneuropathy, a painful complication of diabetes, remains untreatable, emphasizing a critical need for improved therapeutic strategies. Recent evidence suggests that exercise may facilitate recovery of peripheral nerve function in diabetes. However, the mechanism by which exercise protects against diabetes-induced nerve dysfunction is unknown. In this dissertation we hypothesized that forced-exercise protects against experimental DPN by preventing glucose-associated alterations of voltage-gated calcium currents (VGCC) in small diameter dorsal root ganglion (DRG) neurons. Using behavioral, nerve-electrophysiology and patch-clamp methodology we examined the functional consequences of forced-exercise (treadmill, 5.4 km/week) on VGCC in dissociated small diameter DRG neurons from rats conferred diabetic by streptozotocin (STZ) treatment. Exercised-STZ rats in comparison to sedentary-STZ rats, demonstrated a 4 week delay in the onset of tactile hyperalgesia that was independent of changes in blood glucose levels. Interestingly, forced-exercise induced protection against diabetes-induced tactile hyperalgesia was reversed in a dose dependent manner by the opioid antagonist, naloxone. Forced-Exercise also prevented peripheral nerve conduction deficits in STZ-treated rats. Small diameter DRG neurons harvested from sedentary-STZ rats with demonstrated hyperalgesia exhibited 2-fold increase in peak high-voltage activated (HVA) Ca<super>2+</super> current density and low-voltage activated (LVA) Ca<super>2+</super> current component. The steady-state inactivation (SSI) (measure of channel availability) of LVA currents demonstrated a rightward shift in sedentary-STZ rats (+7.5 mV shift; V50 = -50.9 ± 0.6 mV; vehicle treated rats V50 = -58.4 ± 0.9 mV). Forced-exercise prevented the increase in both, peak HVA Ca<super>2+</super> current density and LVA SSI shift (V50 = -58.2 ± 1.4 mV), but did not alter LVA current component. We conclude that forced-exercise delayed the onset of diabetic tactile hyperalgesia by preventing the alteration of VGCCs in small diameter DRG neurons, possibly by decreasing total calcium influx and dampening neuronal over-excitability.</p>","abstract_has_math":false,"creators":["Shankarappa, Sahadev A."],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"Neuroscience","degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2010,"date_issued":"2010-01-01T08:00:00Z","date_published":"2010-01-01T08:00:00Z","updated_at":"2026-07-24T02:55:16Z","subjects":["Calcium","Diabetes","Exercise","Hyperalgesia","Neuropathy","Pain","Neuroscience and Neurobiology"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://ecommons.luc.edu/luc_diss/187","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Shankarappa, Sahadev A."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2016-03-31T17:08:48Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Neuroscience"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Calcium","Diabetes","Exercise","Hyperalgesia","Neuropathy","Pain","Neuroscience and Neurobiology"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://ecommons.luc.edu/luc_diss/187"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["

Exercise is now established as an integral adjunct to the management of diabetes. Diabetic polyneuropathy, a painful complication of diabetes, remains untreatable, emphasizing a critical need for improved therapeutic strategies. Recent evidence suggests that exercise may facilitate recovery of peripheral nerve function in diabetes. However, the mechanism by which exercise protects against diabetes-induced nerve dysfunction is unknown. In this dissertation we hypothesized that forced-exercise protects against experimental DPN by preventing glucose-associated alterations of voltage-gated calcium currents (VGCC) in small diameter dorsal root ganglion (DRG) neurons. Using behavioral, nerve-electrophysiology and patch-clamp methodology we examined the functional consequences of forced-exercise (treadmill, 5.4 km/week) on VGCC in dissociated small diameter DRG neurons from rats conferred diabetic by streptozotocin (STZ) treatment. Exercised-STZ rats in comparison to sedentary-STZ rats, demonstrated a 4 week delay in the onset of tactile hyperalgesia that was independent of changes in blood glucose levels. Interestingly, forced-exercise induced protection against diabetes-induced tactile hyperalgesia was reversed in a dose dependent manner by the opioid antagonist, naloxone. Forced-Exercise also prevented peripheral nerve conduction deficits in STZ-treated rats. Small diameter DRG neurons harvested from sedentary-STZ rats with demonstrated hyperalgesia exhibited 2-fold increase in peak high-voltage activated (HVA) Ca2+ current density and low-voltage activated (LVA) Ca2+ current component. The steady-state inactivation (SSI) (measure of channel availability) of LVA currents demonstrated a rightward shift in sedentary-STZ rats (+7.5 mV shift; V50 = -50.9 ± 0.6 mV; vehicle treated rats V50 = -58.4 ± 0.9 mV). Forced-exercise prevented the increase in both, peak HVA Ca2+ current density and LVA SSI shift (V50 = -58.2 ± 1.4 mV), but did not alter LVA current component. We conclude that forced-exercise delayed the onset of diabetic tactile hyperalgesia by preventing the alteration of VGCCs in small diameter DRG neurons, possibly by decreasing total calcium influx and dampening neuronal over-excitability.

"]},{"key":"dc:title","label":"Title","values":["Forced-Exercise Alleviates Neuropathic Pain in Experimental Diabetes: Effects on Voltage-Gated Calcium Channels"]}]}],"canonical_facts":{"dc:creator":["Shankarappa, Sahadev A."],"dc:date.available":["2016-03-31T17:08:48Z"],"dc:description.abstract":["

Exercise is now established as an integral adjunct to the management of diabetes. Diabetic polyneuropathy, a painful complication of diabetes, remains untreatable, emphasizing a critical need for improved therapeutic strategies. Recent evidence suggests that exercise may facilitate recovery of peripheral nerve function in diabetes. However, the mechanism by which exercise protects against diabetes-induced nerve dysfunction is unknown. In this dissertation we hypothesized that forced-exercise protects against experimental DPN by preventing glucose-associated alterations of voltage-gated calcium currents (VGCC) in small diameter dorsal root ganglion (DRG) neurons. Using behavioral, nerve-electrophysiology and patch-clamp methodology we examined the functional consequences of forced-exercise (treadmill, 5.4 km/week) on VGCC in dissociated small diameter DRG neurons from rats conferred diabetic by streptozotocin (STZ) treatment. Exercised-STZ rats in comparison to sedentary-STZ rats, demonstrated a 4 week delay in the onset of tactile hyperalgesia that was independent of changes in blood glucose levels. Interestingly, forced-exercise induced protection against diabetes-induced tactile hyperalgesia was reversed in a dose dependent manner by the opioid antagonist, naloxone. Forced-Exercise also prevented peripheral nerve conduction deficits in STZ-treated rats. Small diameter DRG neurons harvested from sedentary-STZ rats with demonstrated hyperalgesia exhibited 2-fold increase in peak high-voltage activated (HVA) Ca2+ current density and low-voltage activated (LVA) Ca2+ current component. The steady-state inactivation (SSI) (measure of channel availability) of LVA currents demonstrated a rightward shift in sedentary-STZ rats (+7.5 mV shift; V50 = -50.9 ± 0.6 mV; vehicle treated rats V50 = -58.4 ± 0.9 mV). Forced-exercise prevented the increase in both, peak HVA Ca2+ current density and LVA SSI shift (V50 = -58.2 ± 1.4 mV), but did not alter LVA current component. We conclude that forced-exercise delayed the onset of diabetic tactile hyperalgesia by preventing the alteration of VGCCs in small diameter DRG neurons, possibly by decreasing total calcium influx and dampening neuronal over-excitability.

"],"dc:identifier":["https://ecommons.luc.edu/luc_diss/187"],"dc:subject":["Calcium","Diabetes","Exercise","Hyperalgesia","Neuropathy","Pain","Neuroscience and Neurobiology"],"dc:title":["Forced-Exercise Alleviates Neuropathic Pain in Experimental Diabetes: Effects on Voltage-Gated Calcium Channels"],"thesis:degree_discipline":["Neuroscience"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T02:55:16Z"}