title: Forced-exercise delays neuropathic pain in experimental diabetes: effects on voltage-activated calcium channels.
abstract: Physical exercise produces a variety of psychophysical effects, including altered pain perception. Elevated levels of centrally produced endorphins or endocannabinoids are implicated as mediators of exercise-induced analgesia. The effect of exercise on the development and persistence of disease-associated acute/chronic pain remains unclear. In this study, we quantified the physiological consequence of forced-exercise on the development of diabetes-associated neuropathic pain. Euglycemic control or streptozotocin (STZ)-induced diabetic adult male rats were subdivided into sedentary or forced-exercised (2-10 weeks, treadmill) subgroups and assessed for changes in tactile responsiveness. Two weeks following STZ-treatment, sedentary rats developed a marked and sustained hypersensitivity to von Frey tactile stimulation. By comparison, STZ-treated diabetic rats undergoing forced-exercise exhibited a 4-week delay in the onset of tactile hypersensitivity that was independent of glucose control. Exercise-facilitated analgesia in diabetic rats was reversed, in a dose-dependent manner, by naloxone. Small-diameter (< 30 μm) DRG neurons harvested from STZ-treated tactile hypersensitive diabetic rats exhibited an enhanced (2.5-fold) rightward (depolarizing) shift in peak high-voltage activated (HVA) Ca(2+) current density with a concomitant appearance of a low-voltage activated (LVA) Ca(2+) current component. LVA Ca(2+) currents present in DRG neurons from hypersensitive diabetic rats exhibited a marked depolarizing shift in steady-state inactivation. Forced-exercise attenuated diabetes-associated changes in HVA Ca(2+) current density while preventing the depolarizing shift in steady-state inactivation of LVA Ca(2+) currents. Forced-exercise markedly delays the onset of diabetes-associated neuropathic pain, in part, by attenuating associated changes in HVA and LVA Ca(2+) channel function within small-diameter DRG neurons possibly by altering opioidergic tone.
authors.affiliation: Research Service, Department of Veterans Affairs, Edward Hines Jr. VA Hospital, Hines, Illinois 60141, USA.
authors.forename: Sahadev A
authors.initials: SA
authors.lastname: Shankarappa
authors.forename: Erika S
authors.initials: ES
authors.lastname: Piedras-Rentería
authors.forename: Evan B
authors.initials: EB
authors.lastname: Stubbs
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000378:metabolism* / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism* / Q000628:therapy*; D003929:Diabetic Neuropathies / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control*; D005081:Exercise Therapy / Q000379:methods*; D008297:Male; D009431:Neural Conduction / Q000502:physiology; D010805:Physical Conditioning, Animal / Q000379:methods; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015220:Calcium Channels