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Evidence of Spinal Cord Hyperexcitability as Measured With Nociceptive Flexion Reflex (NFR) Threshold in Chronic Lateral Epicondylalgia With or Without a Positive Neurodynamic Test

  • Edwin Choon Wyn Lim
    Affiliations
    Centre of Clinical Research Excellence: Spine, Division of Physiotherapy, School of Health and Rehabilitation Sciences, University of Queensland, St. Lucia, Australia

    Department of Physiotherapy, Singapore General Hospital, Singapore
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  • Michele Sterling
    Affiliations
    Centre for National Research on Disability and Rehabilitation Medicine (CONROD), University of Queensland, Herston, Australia
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  • Ashley Pedler
    Affiliations
    Centre for National Research on Disability and Rehabilitation Medicine (CONROD), University of Queensland, Herston, Australia
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  • Brooke K. Coombes
    Affiliations
    Centre of Clinical Research Excellence: Spine, Division of Physiotherapy, School of Health and Rehabilitation Sciences, University of Queensland, St. Lucia, Australia
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  • Bill Vicenzino
    Correspondence
    Address reprint requests to Bill Vicenzino, Centre of Clinical Research Excellence: Spine, Division of Physiotherapy, School of Health and Rehabilitation Sciences, University of Queensland, St. Lucia, QLD 4067, Australia.
    Affiliations
    Centre of Clinical Research Excellence: Spine, Division of Physiotherapy, School of Health and Rehabilitation Sciences, University of Queensland, St. Lucia, Australia
    Search for articles by this author

      Abstract

      There is emerging evidence of altered pain signal processing as a likely underlying mechanism in chronic lateral epicondylalgia (LE), yet this remains to be assessed. Furthermore, it has been proposed that neurodynamic tests reflect nociceptive withdrawal responses. Therefore, the objective was to improve our understanding of spinal cord excitability as measured by nociceptive flexion reflex (NFR) threshold in chronic LE with and without a positive neurodynamic test. NFR threshold, pain-free grip, and pressure pain threshold were measured in 30 LE participants and 31 healthy controls. Test of neural tissue involvement (using upper limb neural tension, radial bias) was used to differentiate LE participants with or without a positive neurodynamic test. There were significant differences in NFR threshold between the control and LE with or without a positive neurodynamic test (F[2,54] = 5.68, P = .006), after adjusting for age, sex, pain rating at NFR threshold, and reflex size (NFR interval peak z score). The mean differences (95% confidence interval) in NFR threshold between the control and LE with or without a positive neurodynamic test were 3.74 mA (.637, 6.84) and 3.38 mA (.0245, 6.74) respectively.

      Perspective

      The results suggest evidence of spinal cord hyperexcitability, particularly sensory hypersensitivity, in LE with or without a positive neurodynamic test. Our data appear to support the hypothesis that continued peripheral afferent stimulation results in facilitation of nociceptive pathways in this patient population.

      Key words

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      References

        • Alfredson H.
        • Ljung B.O.
        • Thorsen K.
        • Lorentzon R.
        In vivo investigation of ECRB tendons with microdialysis technique–no signs of inflammation but high amounts of glutamate in tennis elbow.
        Acta Orthop Scand. 2000; 71: 475-479
        • Andersson G.
        • Forsgren S.
        • Scott A.
        • Gaida J.E.
        • Stjernfeldt J.E.
        • Lorentzon R.
        • Alfredson H.
        • Backman C.
        • Danielson P.
        Tenocyte hypercellularity and vascular proliferation in a rabbit model of tendinopathy: Contralateral effects suggest the involvement of central neuronal mechanisms.
        Br J Sports Med. 2011; 45: 399-406
        • Banic B.
        • Petersen-Felix S.
        • Andersen O.K.
        • Radanov B.P.
        • Villiger P.M.
        • Arendt-Nielsen L.
        • Curatolo M.
        Evidence for spinal cord hypersensitivity in chronic pain after whiplash injury and in fibromyalgia.
        Pain. 2004; 107: 7-15
        • Batterham A.M.
        • Hopkins W.G.
        Making meaningful inferences about magnitudes.
        Int J Sports Physiol Perform. 2006; 1: 50-57
        • Bennett M.I.
        • Smith B.H.
        • Torrance N.
        • Potter J.
        The S-LANSS score for identifying pain of predominantly neuropathic origin: Validation for use in clinical and postal research.
        J Pain. 2005; 6: 149-158
        • Bisset L.
        • Beller E.
        • Jull G.
        • Brooks P.
        • Darnell R.
        • Vicenzino B.
        Mobilisation with movement and exercise, corticosteroid injection, or wait and see for tennis elbow: Randomised trial.
        BMJ. 2006; 333: 939
        • Butler D.S.
        The Sensitive Nervous System.
        Unley, South Australia, Noigroup Publications. 2000;
        • Chesterton L.S.
        • van der Windt D.A.
        • Sim J.
        • Lewis M.
        • Mallen C.D.
        • Mason E.E.
        • Warlow C.
        • Vohora K.
        • Hay E.M.
        Transcutaneous electrical nerve stimulation for the management of tennis elbow: A pragmatic randomized controlled trial: the TATE trial (ISRCTN 87141084).
        BMC Musculoskelet Disord. 2009; 10: 156
        • Chiang H.C.
        • Ko Y.C.
        • Chen S.S.
        • Yu H.S.
        • Wu T.N.
        • Chang P.Y.
        Prevalence of shoulder and upper-limb disorders among workers in the fish-processing industry.
        Scand J Work Environ Health. 1993; 19: 126-131
        • Cohen J.
        Statistical Power Analysis for the Behavioral Sciences.
        Lawrence Erlbaum Associates, Hillsdale, NJ1988
        • Coombes B.K.
        • Bisset L.
        • Vicenzino B.
        A new integrative model of lateral epicondylalgia.
        Br J Sports Med. 2009; 43: 252-258
        • Courtney C.A.
        • Lewek M.D.
        • Witte P.O.
        • Chmell S.J.
        • Hornby T.G.
        Heightened flexor withdrawal responses in subjects with knee osteoarthritis.
        J Pain. 2009; 10: 1242-1249
        • Craig A.D.
        Pain mechanisms: Labeled lines versus convergence in central processing.
        Annu Rev Neurosci. 2003; 26: 1-30
        • Descatha A.
        • Roquelaure Y.
        • Chastang J.F.
        • Evanoff B.
        • Cyr D.
        • Leclerc A.
        Description of outcomes of upper-extremity musculoskeletal disorders in workers highly exposed to repetitive work.
        J Hand Surg Am. 2009; 34: 890-895
        • Elvey R.L.
        The investigation of arm pain: Signs of adverse responses to the physical examination of the brachial plexus and related tissues.
        in: Boyling J.D. Palastanga N. Grieve's Modern Manual Therapy. Churchill Livingstone, New York, NY1994: 577-585
        • Fan Z.J.
        • Silverstein B.A.
        • Bao S.
        • Bonauto D.K.
        • Howard N.L.
        • Spielholz P.O.
        • Smith C.K.
        • Polissar N.L.
        • Viikari-Juntura E.
        Quantitative exposure-response relations between physical workload and prevalence of lateral epicondylitis in a working population.
        Am J Ind Med. 2009; 52: 479-490
        • Fernandez-Carnero J.
        • Fernandez-de-Las-Penas C.
        • de la Llave-Rincon A.I.
        • Ge H.Y.
        • Arendt-Nielsen L.
        Widespread mechanical pain hypersensitivity as sign of central sensitization in unilateral epicondylalgia: A blinded, controlled study.
        Clin J Pain. 2009; 25: 555-561
        • Fernandez-Carnero J.
        • Fernandez-de-las-Penas C.
        • Sterling M.
        • Souvlis T.
        • Arendt-Nielsen L.
        • Vicenzino B.
        Exploration of the extent of somato-sensory impairment in patients with unilateral lateral epicondylalgia.
        J Pain. 2009; 10: 1179-1185
        • French D.J.
        • France C.R.
        • France J.L.
        • Arnott L.F.
        The influence of acute anxiety on assessment of nociceptive flexion reflex thresholds in healthy young adults.
        Pain. 2005; 114: 358-363
        • Gruchow H.W.
        • Pelletier D.
        An epidemiologic study of tennis elbow. Incidence, recurrence, and effectiveness of prevention strategies.
        Am J Sports Med. 1979; 7: 234-238
        • Haanpaa M.L.
        • Backonja M.M.
        • Bennett M.I.
        • Bouhassira D.
        • Cruccu G.
        • Hansson P.T.
        • Jensen T.S.
        • Kauppila T.
        • Rice A.S.
        • Smith B.H.
        • Treede R.D.
        • Baron R.
        Assessment of neuropathic pain in primary care.
        Am J Med. 2009; 122: S13-21
        • Hamilton P.G.
        The prevalence of humeral epicondylitis: A survey in general practice.
        J R Coll Gen Pract. 1986; 36: 464-465
        • Herrero J.F.
        • Cervero F.
        Changes in nociceptive reflex facilitation during carrageenan-induced arthritis.
        Brain Res. 1996; 717: 62-68
        • Larson A.A.
        • Giovengo S.L.
        • Russell I.J.
        • Michalek J.E.
        Changes in the concentrations of amino acids in the cerebrospinal fluid that correlate with pain in patients with fibromyalgia: Implications for nitric oxide pathways.
        Pain. 2000; 87: 201-211
        • Lim E.C.
        • Sterling M.
        • Stone A.
        • Vicenzino B.
        Central hyperexcitability as measured with nociceptive flexor reflex threshold in chronic musculoskeletal pain: A systematic review.
        Pain. 2011; 152: 1811-1820
        • Lindstedt F.
        • Berrebi J.
        • Greayer E.
        • Lonsdorf T.B.
        • Schalling M.
        • Ingvar M.
        • Kosek E.
        Conditioned pain modulation is associated with common polymorphisms in the serotonin transporter gene.
        PLoS One. 2011; 6: e18252
        • Ma Q.P.
        • Tian L.
        • Woolf C.J.
        Resection of sciatic nerve re-triggers central sprouting of A-fibre primary afferents in the rat.
        Neurosci Lett. 2000; 288: 215-218
        • Nee R.J.
        • Butler D.
        Management of peripheral neuropathic pain: Integrating neurobiology, neurodynamics, and clinical evidence.
        Phys Ther Sport. 2006; 7: 36-49
        • Neziri A.Y.
        • Curatolo M.
        • Nuesch E.
        • Scaramozzino P.
        • Andersen O.K.
        • Arendt-Nielsen L.
        • Juni P.
        Factor analysis of responses to thermal, electrical, and mechanical painful stimuli supports the importance of multi-modal pain assessment.
        Pain. 2011; 152: 1146-1155
        • Nickel F.T.
        • DeCol R.
        • Jud S.
        • Fasching P.A.
        • Seifert F.
        • Maihofner C.
        Inhibition of hyperalgesia by conditioning electrical stimulation in a human pain model.
        Pain. 2011; 152: 1298-1303
        • Nishioka K.
        • Harada Y.
        • Kitahata L.M.
        • Tsukahara S.
        • Collins J.G.
        Role of WDR neurons in a hind limb noxious heat evoked flexion withdrawal reflex.
        Life Sci. 1995; 56: 485-489
        • Paungmali A.
        • O'Leary S.
        • Souvlis T.
        • Vicenzino B.
        Hypoalgesic and sympathoexcitatory effects of mobilization with movement for lateral epicondylalgia.
        Phys Ther. 2003; 83: 374-383
        • Rhudy J.L.
        • France C.R.
        Defining the nociceptive flexion reflex (NFR) threshold in human participants: A comparison of different scoring criteria.
        Pain. 2007; 128: 244-253
        • Rhudy J.L.
        • France C.R.
        Reliability and validity of a brief method to assess nociceptive flexion reflex (NFR) threshold.
        J Pain. 2011; 12: 782-791
        • Rompe J.D.
        • Overend T.J.
        • MacDermid J.C.
        Validation of the Patient-rated Tennis Elbow Evaluation Questionnaire.
        J Hand Ther. 2007; 20 (quiz 11): 3-10
        • Ruiz-Ruiz B.
        • Fernandez-de-Las-Penas C.
        • Ortega-Santiago R.
        • Arendt-Nielsen L.
        • Madeleine P.
        Topographical pressure and thermal pain sensitivity mapping in patients with unilateral lateral epicondylalgia.
        J Pain. 2011; 12: 1040-1048
        • Schmid A.B.
        • Brunner F.
        • Luomajoki H.
        • Held U.
        • Bachmann L.M.
        • Kunzer S.
        • Coppieters M.W.
        Reliability of clinical tests to evaluate nerve function and mechanosensitivity of the upper limb peripheral nervous system.
        BMC Musculoskelet Disord. 2009; 10: 11
        • Shiri R.
        • Viikari-Juntura E.
        • Varonen H.
        • Heliovaara M.
        Prevalence and determinants of lateral and medial epicondylitis: A population study.
        Am J Epidemiol. 2006; 164: 1065-1074
        • Slater H.
        • Arendt-Nielsen L.
        • Wright A.
        • Graven-Nielsen T.
        Sensory and motor effects of experimental muscle pain in patients with lateral epicondylalgia and controls with delayed onset muscle soreness.
        Pain. 2005; 114: 118-130
        • Smidt N.
        • Assendelft W.J.
        • van der Windt D.A.
        • Hay E.M.
        • Buchbinder R.
        • Bouter L.M.
        Corticosteroid injections for lateral epicondylitis: A systematic review.
        Pain. 2002; 96: 23-40
        • Smidt N.
        • van der Windt D.A.
        • Assendelft W.J.
        • Mourits A.J.
        • Deville W.L.
        • de Winter A.F.
        • Bouter L.M.
        Interobserver reproducibility of the assessment of severity of complaints, grip strength, and pressure pain threshold in patients with lateral epicondylitis.
        Arch Phys Med Rehabil. 2002; 83: 1145-1150
        • Sterling M.
        Differential development of sensory hypersensitivity and a measure of spinal cord hyperexcitability following whiplash injury.
        Pain. 2010; 150: 501-506
        • Sterling M.
        • Hodkinson E.
        • Pettiford C.
        • Souvlis T.
        • Curatolo M.
        Psychologic factors are related to some sensory pain thresholds but not nociceptive flexion reflex threshold in chronic whiplash.
        Clin J Pain. 2008; 24: 124-130
        • Sterling M.
        • Jull G.
        • Vicenzino B.
        • Kenardy J.
        Sensory hypersensitivity occurs soon after whiplash injury and is associated with poor recovery.
        Pain. 2003; 104: 509-517
        • Sterling M.
        • Treleaven J.
        • Jull G.
        Responses to a clinical test of mechanical provocation of nerve tissue in whiplash associated disorder.
        Man Ther. 2002; 7: 89-94
        • Stratford P.
        • Levy D.
        • Gowland C.
        Evaluative properties of measures used to assess patients with lateral epicondylitis at the elbow.
        Physiother Canada. 1993; 45: 160-164
        • Stratford P.W.
        • Levy D.R.
        • Sports C.J.
        Assessing valid change over time in patients with lateral epicondylitis at the elbow.
        Clin J Sports Med. 1994; 4: 88-91
        • Stratford P.W.
        • Norman G.R.
        • McIntosh J.M.
        Generalizability of grip strength measurements in patients with tennis elbow.
        Phys Ther. 1989; 69: 276-281
        • Verhaar J.A.
        Tennis elbow. Anatomical, epidemiological and therapeutic aspects.
        Int Orthop. 1994; 18: 263-267
        • Vicenzino B.
        • Collins D.
        • Benson H.
        • Wright A.
        An investigation of the interrelationship between manipulative therapy-induced hypoalgesia and sympathoexcitation.
        J Manipulative Physiol Ther. 1998; 21: 448-453
        • Vicenzino B.
        • Collins D.
        • Wright A.
        The initial effects of a cervical spine manipulative physiotherapy treatment on the pain and dysfunction of lateral epicondylalgia.
        Pain. 1996; 68: 69-74
        • Vicenzino B.
        • Souvlis T.
        • Wright A.
        Musculoskeletal pain.
        in: Strong J. Unruh A.M. Wright A. Baxter G.D. Pain: A Textbook For Therapists. Churchill Livingstone, New York, NY2002: 332-333 (338-340)
        • Wainner R.S.
        • Fritz J.M.
        • Irrgang J.J.
        • Boninger M.L.
        • Delitto A.
        • Allison S.
        Reliability and diagnostic accuracy of the clinical examination and patient self-report measures for cervical radiculopathy.
        Spine. 2003; 28: 52-62
        • Weingarten T.N.
        • Watson J.C.
        • Hooten W.M.
        • Wollan P.C.
        • Melton III, L.J.
        • Locketz A.J.
        • Wong G.Y.
        • Yawn B.P.
        Validation of the S-LANSS in the community setting.
        Pain. 2007; 132: 189-194
        • Woolf C.J.
        Evidence for a central component of post-injury pain hypersensitivity.
        Nature. 1983; 306: 686-688
        • Woolf C.J.
        Central sensitization: Implications for the diagnosis and treatment of pain.
        Pain. 2011; 152: S2-15
        • Woolf C.J.
        • Shortland P.
        • Coggeshall R.E.
        Peripheral nerve injury triggers central sprouting of myelinated afferents.
        Nature. 1992; 355: 75-78
        • Wright A.
        • Thurnwald P.
        • O'Callaghan J.
        • Smith J.
        • Vicenzino B.
        Hyperalgesia in tennis elbow patients.
        J Musculoskelet Pain. 1994; 2: 83-97
        • Yaxley G.
        • Jull G.
        Adverse tension in the neural system. A preliminary study in patients with tennis elbow.
        Aust J Physiother. 1993; 39: 15-22
        • Zachariae R.
        • Andersen O.K.
        • Bjerring P.
        • Jorgensen M.M.
        • Arendt-Nielsen L.
        Effects of an opioid antagonist on pain intensity and withdrawal reflexes during induction of hypnotic analgesia in high- and low-hypnotizable volunteers.
        Eur J Pain. 1998; 2: 25-34