Exercise-Induced Modulation of Pain in Adults With and Without Painful Diabetic Neuropathy


      The purpose of this study was to examine exercise-induced pain modulation in diabetic adults with painful diabetic neuropathy (PDN) compared to diabetic adults without PDN. Eighteen adults diagnosed with type 2 diabetes with and without PDN (mean age of 49 years) completed 2 sessions. During the familiarization session, participants completed questionnaires, were familiarized with the pain testing protocols, and completed maximal isometric contractions. During the exercise session, experimental pain testing was completed before and following exercise consisting of 3 minutes of isometric exercise performed at 25% maximal voluntary contraction. Ratings of perceived exertion and muscle pain were assessed every 30 seconds during exercise. Results indicated that ratings of perceived exertion and muscle pain during exercise were significantly higher (P < .05) for diabetic adults with PDN versus diabetic adults without PDN. Diabetic adults with PDN did not experience changes in thermal pain ratings following exercise, whereas diabetic adults without PDN reported significantly lower pain ratings following exercise. It is concluded that diabetic adults with PDN experienced high levels of muscle pain during exercise and a lack of exercise-induced hypoalgesia following exercise, in comparison to diabetic adults without PDN, who experienced lower levels of muscle pain during exercise and a hypoalgesic response following exercise.


      Very little research has been conducted examining the impact of exercise on pain modulation in diabetic adults with PDN. This study provides support that adults with PDN exhibit exercise-induced endogenous pain modulatory system dysfunction.

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        • Apelqvist J.
        • Bakker K.
        • van Houtum W.H.
        • Schaper N.C.
        Practical guidelines on the management and prevention of the diabetic foot.
        Diabetes Metab Res Rev. 2008; 24: 181-187
        • Argoff C.E.
        • Cole B.E.
        • Fishbain D.A.
        • Irving G.A.
        Diabetic peripheral neuropathic pain: Clinical and quality-of-life issues.
        Mayo Clin Proc. 2006; 81: S3-S11
        • Backonja M.
        • Woolf C.J.
        Future directions in neuropathic pain therapy: Closing the translational loop.
        Oncologist. 2010; 15: 24-29
        • Baron R.
        Peripheral neuropathic pain: From mechanisms to symptoms.
        Clin J Pain. 2000; 16: 12-20
        • Bartholomew J.B.
        • Lewis B.P.
        • Linder D.E.
        • Cook D.B.
        Post-exercise analgesia: Replication and extension.
        J Sports Sci. 1996; 14: 329-334
        • Booth M.L.
        Assessment of physical activity: An international perspective.
        Res Q Exerc Sport. 2000; 71: s114-s120
        • Borg G.
        The Borg RPE Scale.
        in: Borg G. Borg's Perceived Exertion and Pain Scales. Human Kinetics, Champaign, IL1998: 29-38
        • Bouhassira D.
        • Attal N.
        • Fermanian J.
        • Alchaar H.
        • Gautron M.
        • Masquelier E.
        • Rostaing S.
        • Lanteri-Minet M.
        • Collin E.
        • Grisart J.
        • Boureau F.
        Development and validation of the Neuropathic Pain Screening Inventory.
        Pain. 2004; 108: 248-257
        • Chen X.
        • Levine J.D.
        Altered temporal pattern of mechanically evoked C-fiber activity in a model of diabetic neuropathy in the rat.
        Neuroscience. 2003; 121: 1007-1015
        • Cook D.B.
        • O’Connor P.J.
        • Eubanks S.A.
        • Smith J.C.
        • Lee M.
        Naturally occurring muscle pain during exercise: Assessment and experimental evidence.
        Med Sci Sports Exerc. 1997; 29: 999-1012
        • Cook D.B.
        • Koltyn K.F.
        Pain and exercise.
        Int J Sport Psychol. 2000; 31: 256-277
        • Cook D.B.
        • Stegner A.J.
        • Ellingson L.D.
        Exercise alters pain sensitivity in gulf war veterans with chronic musculoskeletal pain.
        J Pain. 2010; 11: 764-772
        • Craig C.L.
        • Marshall A.L.
        • Sjöström M.
        • Bauman A.E.
        • Booth M.L.
        • Ainsworth B.E.
        • Pratt M.
        • Ekelund U.
        • Yngve A.
        • Sallis J.F.
        • Oja P.
        International Physical Activity Questionnaire: 12-country reliability and validity.
        Med Sci Sports Exerc. 2003; 35: 1381-1395
        • Freynhagen R.
        • Baron R.
        • Gockel U.
        • Tölle T.R.
        painDETECT: A new screening questionnaire to identify neuropathic components in patients with back pain.
        Curr Med Res Opin. 2006; 22: 1911-1920
        • Hagströmer M.
        • Oja P.
        • Sjöström M.
        The International Physical Activity Questionnaire: A study of concurrent and construct validity.
        Public Health Nutr. 2006; 9: 755-762
        • Janal M.N.
        Pain sensitivity, exercise and stoicism.
        J R Soc Med. 1996; 89: 376-381
        • Jensen T.S.
        • Gottrup H.
        • Sindrup S.H.
        • Bach F.W.
        The clinical picture of neuropathic pain.
        Eur J Pharmacol. 2001; 429: 1-11
        • Kadetoff D.
        • Kosek E.
        The effects of static muscular contraction on blood pressure, heart rate, pain ratings, and pressure pain thresholds in healthy individuals and patients with fibromyalgia.
        Eur J Pain. 2007; 11: 39-47
        • Kluding P.M.
        • Pasnoor M.
        • Singh R.
        • Jernigan S.
        • Farmer K.
        • Rucker J.
        • Sharma N.K.
        • Wright D.E.
        The effect of exercise on neuropathic symptoms, nerve fiber function, and cutaneous innervations in people with diabetic peripheral neuropathy.
        J Diabetes Complications. 2012; 26: 424-429
        • Knauf M.T.
        • Koltyn K.F.
        Exercise-induced modulation of pain.
        Med Sci Sports Exerc. 2010; 42: 660
        • Knauf M.T.
        • Koltyn K.F.
        Exercise-induced pain modulation in adults with painful diabetic peripheral neuropathy.
        J Pain. 2012; 13: S32
        • Koltyn K.F.
        • Arbogast R.W.
        Perception of pain after resistance exercise.
        Br J Sports Med. 1998; 32: 20-24
        • Koltyn K.F.
        Analgesia following exercise: A review.
        Sports Med. 2000; 29: 85-98
        • Koltyn K.F.
        Exercise-induced hypoalgesia and intensity of exercise.
        Sports Med. 2002; 32: 477-487
        • Koltyn K.F.
        • Umeda M.
        Exercise, hypoalgesia, and blood pressure.
        Sports Med. 2006; 36: 207-214
        • Kosek E.
        • Ekholm J.
        • Hansson P.
        Modulation of pressure pain thresholds during and following isometric contraction in patients with fibromyalgia and in healthy controls.
        Pain. 1996; 64: 415-423
        • Krause S.J.
        • Backonja M.M.
        Development of a neuropathic pain questionnaire.
        Clin J Pain. 2003; 19: 306-314
        • Kuphal K.E.
        • Fibuch E.E.
        • Taylor B.K.
        Extended swimming exercise reduces inflammatory and peripheral neuropathic pain in rodents.
        J Pain. 2007; 8: 989-997
        • Lannersten L.
        • Kosek E.
        Dysfunction of endogenous pain inhibition during exercise with painful muscles in patients with shoulder myalgia and fibromyalgia.
        Pain. 2010; 151: 77-86
        • McNair D.M.
        • Lorr M.
        • Droppleman L.F.
        Profile of Mood States.
        Educational and Industrial Testing Service, San Diego, CA1971
        • Melzack R.
        The Short-Form McGill Pain Questionnaire.
        Pain. 1987; 30: 191-197
        • Mohn C.
        • Vassend O.
        • Knardahl S.
        Experimental pain sensitivity in women with temporomandibular disorders and pain-free controls: The relationship to orofacial muscular contraction and cardiovascular responses.
        Clin J Pain. 2008; 24: 343-352
        • Morrato E.H.
        • Hill J.O.
        • Wyatt H.R.
        • Ghushchyan V.
        • Sullivan P.
        Physical activity in U.S. adults with diabetes and at risk for developing diabetes, 2003.
        Diabetes Care. 2007; 30: 203-209
        • Nijs J.
        • Kosek E.
        • Van Oosterwijck J.
        • Meeus M.
        Dysfunctional endogenous analgesia during exercise in patients with chronic pain: Exercise or not to exercise?.
        Pain Physician. 2012; 15: ES205-ES213
        • O’Connor P.J.
        • Cook D.B.
        Exercise and pain: The neurobiology, measurement, and laboratory study of pain in relation to exercise in humans.
        Exerc Sport Sci Rev. 1999; 27: 119-166
        • Ørstavik K.
        • Namer B.
        • Schmidt R.
        • Schmelz M.
        • Hilliges M.
        • Weidner C.
        • Carr R.W.
        • Handwerker H.
        • Jørum E.
        • Torebjörk H.E.
        Abnormal function of C-fibers in patients with diabetic neuropathy.
        J Neurosci. 2006; 26: 11287-11294
        • Rossi D.M.
        • Valenti V.E.
        • Navega M.T.
        Exercise training attenuates acute hyperalgesia streptozotocin-induced diabetic female rats.
        Clinics (Sao Paulo). 2011; 66: 1615-1619
        • Shankarappa S.A.
        • Piedras-Rentería E.S.
        • Stubbs Jr., E.B.
        Forced-exercise delays neuropathic pain in experimental diabetes effects on voltage-activated calcium channels.
        J Neurochem. 2011; 118: 224-236
        • Shultz J.A.
        • Sprague M.A.
        • Branen L.J.
        • Lambeth S.
        A comparison of views of individuals with type 2 diabetes mellitus and diabetes educators about barriers to diet and exercise.
        J Health Commun. 2001; 6: 99-115
        • Stagg N.J.
        • Mata H.P.
        • Ibrahim M.M.
        • Henriksen E.J.
        • Porreca F.
        • Vanderah T.W.
        • Philip Malan Jr., T.
        Regular exercise reverses sensory hypersensitivity in a rat neuropathic pain model: Role of endogenous opioids.
        Anesthesiology. 2011; 114: 940-948
        • Staud R.
        • Robinson M.E.
        • Vierck C.J.
        • Cannon R.C.
        • Mauderli A.P.
        • Price D.D.
        Ratings of experimental pain and pain-related negative affect predict clinical pain in patients with fibromyalgia syndrome.
        Pain. 2003; 105: 215-222
        • Staud R.
        • Robinson M.E.
        • Price D.D.
        Isometric exercise has opposite effects on central pain mechanisms in fibromyalgia patients compared to normal controls.
        Pain. 2005; 118: 176-184
        • Staud R.
        • Price D.D.
        • Fillingham R.B.
        Advanced continuous-contact heat pulse design for efficient temporal summation of second pain (windup).
        J Pain. 2006; 7: 575-582
        • Thomas N.
        • Alder E.
        • Leese G.P.
        Barriers to physical activity in patients with diabetes.
        Postgrad Med J. 2004; 80: 287-291
        • Tudor-Locke C.
        • Bassett Jr., D.R.
        How many steps/day are enough? Preliminary pedometer indices for public health.
        Sports Med. 2004; 34: 1-8
        • Umeda M.
        • Newcomb L.W.
        • Ellingson L.D.
        • Koltyn K.F.
        Examination of the dose-response relationship between pain perception and blood pressure following isometric exercise.
        Med Sci Sports Exerc. 2008; 40: 117
        • Van Oosterwijck J.
        • Nijs J.
        • Meeus M.
        • Paul L.
        Evidence for central sensitization in chronic whiplash: A systematic literature review.
        Eur J Pain. 2012; 17: 299-312
        • Veves A.
        • Backonja M.
        • Malik R.A.
        Painful diabetic neuropathy: Epidemiology, natural history, early diagnosis, and treatment options.
        Pain Med. 2008; 9: 660-674
        • Vierck C.J.
        • Staud R.
        • Price D.D.
        • Connon R.L.
        • Mauderli A.P.
        • Martin A.D.
        The effect of maximal exercise on temporal summation of second pain (windup) in patients with fibromyalgia syndrome.
        J Pain. 2001; 2: 334-344
        • Witting N.
        • Svensson P.
        • Jensen T.
        Differential recruitment of endogenous pain inhibitory systems in neuropathic pain patients.
        Pain. 2003; 103: 75-81
        • Yeomans D.C.
        • Cooper B.Y.
        • Vierck C.J.
        Effects of systematic morphine on responses of primates to first or second pain sensations.
        Pain. 1996; 66: 253-263