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Characterization of Pain in Familial Amyloid Polyneuropathy

  • Sophie Ng Wing Tin
    Affiliations
    Université Paris Est Créteil, Faculté de Médecine, EA 4391, Créteil, France

    Assistance Publique–Hôpitaux de Paris, Hôpital Avicenne, Service de Physiologie, Explorations Fonctionnelles et Médecine du Sport, Bobigny, France
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  • Violaine Planté-Bordeneuve
    Affiliations
    Réseau Amylose Henri-Mondor, Hôpital Henri Mondor, Créteil, France

    Assistance Publique–Hôpitaux de Paris, Hôpital Henri Mondor, Service de Neurologie, Créteil, France
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  • Hayet Salhi
    Affiliations
    Université Paris Est Créteil, Faculté de Médecine, EA 4391, Créteil, France

    Réseau Amylose Henri-Mondor, Hôpital Henri Mondor, Créteil, France

    Assistance Publique–Hôpitaux de Paris, Hôpital Henri Mondor, Service de Neurologie, Créteil, France
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  • Colette Goujon
    Affiliations
    Université Paris Est Créteil, Faculté de Médecine, EA 4391, Créteil, France

    Assistance Publique–Hôpitaux de Paris, Hôpital Henri Mondor, Service de Neurochirurgie, Créteil, France
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  • Thibaud Damy
    Affiliations
    Réseau Amylose Henri-Mondor, Hôpital Henri Mondor, Créteil, France

    Assistance Publique–Hôpitaux de Paris, Hôpital Henri Mondor, Service de Cardiologie, Créteil, France
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  • Jean-Pascal Lefaucheur
    Correspondence
    Address reprint requests to Jean-Pascal Lefaucheur, MD, PhD, Hôpital Henri Mondor, Service de Physiologie–Explorations Fonctionnelles, 51 avenue de Lattre de Tassigny, 94010 Créteil cedex, France.
    Affiliations
    Université Paris Est Créteil, Faculté de Médecine, EA 4391, Créteil, France

    Réseau Amylose Henri-Mondor, Hôpital Henri Mondor, Créteil, France

    Assistance Publique–Hôpitaux de Paris, Hôpital Henri Mondor, Service de Physiologie, Explorations Fonctionnelles, Créteil, France
    Search for articles by this author
Published:August 17, 2015DOI:https://doi.org/10.1016/j.jpain.2015.07.010

      Highlights

      • Various mechanisms may be at the origin of pain in familial amyloid polyneuropathy.
      • The painful nature of amyloid neuropathy is not determined by small-fiber lesions.
      • Burning pain sensation may result from peripheral sensitization of small fibers.
      • As small-fiber loss progresses, other types of pain may develop.
      • Central sensitization driven by relatively spared large fibers may play a key role.

      Abstract

      Familial amyloid polyneuropathy (FAP) caused by transthyretin (TTR) mutation is a small-fiber predominant polyneuropathy, exposing patients with TTR-FAP to development of neuropathic pain. However, the painful nature of TTR-FAP has never been specifically addressed. In this study, we compared 2 groups of 16 patients with either painless or painful TTR-FAP with regard to various clinical and neurophysiologic variables, including laser evoked potential (LEP) recording and quantitative sensory testing. The 2 groups of patients did not differ on any clinical or neurophysiologic variable. Patients with painful TTR-FAP complained of ongoing burning pain sensations, pain aggravation at rest, paroxysmal pain (electric shock and stabbing sensations), or provoked pain (mostly dynamic mechanical allodynia). However, the symptomatic presentation of painful TTR-FAP evolved with the course of the disease. The duration of the disease and the severity of small-fiber lesions (increase in thermal thresholds and reduction in LEP amplitude) correlated negatively with the intensity of ongoing burning sensations and positively with the intensity of paroxysmal pain. In addition, small-fiber preservation correlated positively with cold allodynia and pain aggravation at rest and negatively with dynamic mechanical allodynia. Peripheral sensitization of small-diameter nociceptive axons might occur in early TTR-FAP and be responsible for the burning sensation and cold allodynia. As polyneuropathy and small-fiber loss progress, paroxysmal pain and dynamic mechanical allodynia may develop as a result of central sensitization generated by abnormal activities affecting relatively spared large-diameter sensory fibers.

      Perspective

      Pain in TTR-FAP includes several mechanisms varying with the course of the disease and the involvement of the different types of nerve fibers.

      Key words

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      References

        • Amir R.
        • Devor M.
        Functional cross-excitation between afferent A- and C-neurons in dorsal root ganglia.
        Neuroscience. 2000; 95: 189-195
        • Bachmann C.G.
        • Rolke R.
        • Scheidt U.
        • Stadelmann C.
        • Sommer M.
        • Pavlakovic G.
        • Happe S.
        • Treede R.D.
        • Paulus W.
        Thermal hypoaesthesia differentiates secondary restless legs syndrome associated with small fibre neuropathy from primary restless legs syndrome.
        Brain. 2010; 133: 762-770
        • Backonja M.M.
        • Attal N.
        • Baron R.
        • Bouhassira D.
        • Drangholt M.
        • Dyck P.J.
        • Edwards R.R.
        • Freeman R.
        • Gracely R.
        • Haanpaa M.H.
        • Hansson P.
        • Hatem S.M.
        • Krumova E.K.
        • Jensen T.S.
        • Maier C.
        • Mick G.
        • Rice A.S.
        • Rolke R.
        • Treede R.D.
        • Serra J.
        • Toelle T.
        • Tugnoli V.
        • Walk D.
        • Walalce M.S.
        • Ware M.
        • Yarnitsky D.
        • Ziegler D.
        Value of quantitative sensory testing in neurological and pain disorders: NeuPSIG consensus.
        Pain. 2013; 154: 1807-1819
        • Baron R.
        • Binder A.
        • Wasner G.
        Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment.
        Lancet Neurol. 2010; 9: 807-819
        • Benes H.
        • Walters A.S.
        • Allen R.P.
        • Hening W.A.
        • Kohnen R.
        Definition of restless legs syndrome, how to diagnose it, and how to differentiate it from RLS mimics.
        Mov Disord. 2007; 22: S401-S408
        • Bouhassira D.
        • Attal N.
        • Alchaar H.
        • Boureau F.
        • Brochet B.
        • Bruxelle J.
        • Cunin G.
        • Fermanian J.
        • Ginies P.
        • Grun-Overdyking A.
        • Jafari-Schluep H.
        • Lantéri-Minet M.
        • Laurent B.
        • Mick G.
        • Serrie A.
        • Valade D.
        • Vicaut E.
        Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4).
        Pain. 2005; 114: 29-36
        • 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 Symptom Inventory.
        Pain. 2004; 108: 248-257
        • Bouhassira D.
        • Attal N.
        • Willer J.C.
        • Brasseur L.
        Painful and painless peripheral sensory neuropathies due to HIV infection: a comparison using quantitative sensory evaluation.
        Pain. 1999; 80: 265-272
        • Craig A.D.
        Pain mechanisms: labeled lines versus convergence in central processing.
        Annu Rev Neurosci. 2003; 26: 1-30
        • Denier C.
        • Ducot B.
        • Husson H.
        • Lozeron P.
        • Adams D.
        • Meyer L.
        • Said G.
        • Planté-Bordeneuve V.
        A brief compound test for assessment of autonomic and sensory-motor dysfunction in familial amyloid polyneuropathy.
        J Neurol. 2007; 254: 1684-1688
        • Devigili G.
        • Tugnoli V.
        • Penza P.
        • Camozzi F.
        • Lombardi R.
        • Melli G.
        • Broglio L.
        • Granieri E.
        • Lauria G.
        The diagnostic criteria for small fibre neuropathy: from symptoms to neuropathology.
        Brain. 2008; 131: 1912-1925
        • Dyck P.J.
        • Davies J.L.
        • Litchy W.J.
        • O'Brien P.C.
        Longitudinal assessment of diabetic polyneuropathy using a composite score in the Rochester Diabetic Neuropathy Study cohort.
        Neurology. 1997; 49: 229-239
        • Faber C.G.
        • Hoeijmakers J.G.
        • Ahn H.S.
        • Cheng X.
        • Han C.
        • Choi J.S.
        • Estacion M.
        • Lauria G.
        • Vanhoutte E.K.
        • Gerrits M.M.
        • Dib-Hajj S.
        • Drenth J.P.
        • Waxman S.G.
        • Merkies I.S.
        Gain of function Naν1.7 mutations in idiopathic small fiber neuropathy.
        Ann Neurol. 2012; 71: 26-39
        • Fields H.L.
        • Rowbotham M.
        • Baron R.
        Postherpetic neuralgia: irritable nociceptors and deafferentation.
        Neurobiol Dis. 1998; 5: 209-227
        • Fruhstorfer H.
        • Lindblom U.
        • Schmidt W.C.
        Method for quantitative estimation of thermal thresholds in patients.
        J Neurol Neurosurg Psychiatry. 1976; 39: 1071-1075
        • Geber C.
        • Breimhorst M.
        • Burbach B.
        • Egenolf C.
        • Baier B.
        • Fechir M.
        • Koerber J.
        • Treede R.D.
        • Vogt T.
        • Birklein F.
        Pain in chemotherapy-induced neuropathy–more than neuropathic?.
        Pain. 2013; 154: 2877-2887
        • Gemignani F.
        • Brindani F.
        • Negrotti A.
        • Vitetta F.
        • Alfieri S.
        • Marbini A.
        Restless legs syndrome and polyneuropathy.
        Mov Disord. 2006; 21: 1254-1257
        • Gemignani F.
        • Brindani F.
        • Vitetta F.
        • Marbini A.
        Restless legs syndrome and painful neuropathy-retrospective study. A role for nociceptive deafferentation?.
        Pain Med. 2009; 10: 1481-1486
        • Gemignani F.
        • Brindani F.
        • Vitetta F.
        • Marbini A.
        • Calzetti S.
        Restless legs syndrome in diabetic neuropathy: a frequent manifestation of small fiber neuropathy.
        J Peripher Nerv Syst. 2007; 12: 50-53
        • Graham R.C.
        • Hughes R.A.
        A modified peripheral neuropathy scale: the Overall Neuropathy Limitations Scale.
        J Neurol Neurosurg Psychiatry. 2006; 77: 973-976
        • Hatem S.M.
        • Attal N.
        • Ducreux D.
        • Gautron M.
        • Parker F.
        • Plaghki L.
        • Bouhassira D.
        Clinical, functional and structural determinants of central pain in syringomyelia.
        Brain. 2010; 133: 3409-3422
        • Hattan E.
        • Chalk C.
        • Postuma R.B.
        Is there a higher risk of restless legs syndrome (RLS) in peripheral neuropathy?.
        Neurology. 2009; 72: 955-960
        • Iannaccone S.
        • Zucconi M.
        • Marchettini P.
        • Ferini-Strambi L.
        • Nemni R.
        • Quattrini A.
        • Palazzi S.
        • Lacerenza M.
        • Formaglio F.
        • Smirne S.
        Evidence of peripheral axonal neuropathy in primary restless legs syndrome.
        Mov Disord. 1995; 10: 2-9
        • Krämer H.H.
        • Rolke R.
        • Bickel A.
        • Birklein F.
        Thermal thresholds predict painfulness of diabetic neuropathies.
        Diabetes Care. 2004; 27: 2386-2391
        • Krishnan S.T.
        • Quattrini C.
        • Jeziorska M.
        • Malik R.A.
        • Rayman G.
        Abnormal LDI flare but normal quantitative sensory testing and dermal nerve fiber density in patients with painful diabetic neuropathy.
        Diabetes Care. 2009; 32: 451-455
        • Lefaucheur J.P.
        • Ahdab R.
        • Ayache S.S.
        • Lefaucheur-Ménard I.
        • Rouie D.
        • Tebbal D.
        • Neves D.O.
        • Ciampi de Andrade D.
        Pain-related evoked potentials: a comparative study between electrical stimulation using a concentric planar electrode and laser stimulation using a CO2 laser.
        Neurophysiol Clin. 2012; 42: 199-206
        • Lefaucheur J.P.
        • Ng Wing Tin S.
        • Kerschen P.
        • Damy T.
        • Planté-Bordeneuve V.
        Neurophysiological markers of small fibre neuropathy in TTR-FAP mutation carriers.
        J Neurol. 2013; 260: 1497-1503
        • Llewelyn J.G.
        • Gilbey S.G.
        • Thomas P.K.
        • King R.H.
        • Muddle J.R.
        • Watkins P.J.
        Sural nerve morphometry in diabetic autonomic and painful sensory neuropathy. A clinicopathological study.
        Brain. 1991; 114: 867-892
        • Malik R.A.
        • Veves A.
        • Walker D.
        • Siddique I.
        • Lye R.H.
        • Schady W.
        • Boulton A.J.
        Sural nerve fibre pathology in diabetic patients with mild neuropathy: relationship to pain, quantitative sensory testing and peripheral nerve electrophysiology.
        Acta Neuropathol. 2001; 101: 367-374
        • Martin C.
        • Solders G.
        • Sönnerborg A.
        • Hansson P.
        Painful and non-painful neuropathy in HIV-infected patients: an analysis of somatosensory nerve function.
        Eur J Pain. 2003; 7: 23-31
        • Martinez V.
        • Fletcher D.
        • Martin F.
        • Orlikowski D.
        • Sharshar T.
        • Chauvin M.
        • Bouhassira D.
        • Attal N.
        Small fibre impairment predicts neuropathic pain in Guillain-Barré syndrome.
        Pain. 2010; 151: 53-60
        • Meyer-Rosberg K.
        • Kvarnström A.
        • Kinnman E.
        • Gordh T.
        • Nordfors L.O.
        • Kristofferson A.
        Peripheral neuropathic pain–a multidimensional burden for patients.
        Eur J Pain. 2001; 5: 379-389
        • Ng Wing Tin S.
        • Ciampi de Andrade D.
        • Goujon C.
        • Planté-Bordeneuve V.
        • Créange A.
        • Lefaucheur J.P.
        Sensory correlates of pain in peripheral neuropathies.
        Clin Neurophysiol. 2014; 125: 1048-1058
        • Nineb A.
        • Rosso C.
        • Dumurgier J.
        • Nordine T.
        • Lefaucheur J.P.
        • Créange A.
        Restless legs syndrome is frequently overlooked in patients being evaluated for polyneuropathies.
        Eur J Neurol. 2007; 14: 788-792
        • Oaklander A.L.
        • Herzog Z.D.
        • Downs H.M.
        • Klein M.M.
        Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia.
        Pain. 2013; 154: 2310-2316
        • Oaklander A.L.
        • Klein M.M.
        Evidence of small-fiber polyneuropathy in unexplained, juvenile-onset, widespread pain syndromes.
        Pediatrics. 2013; 131: e1091-e1100
        • Otto M.
        • Bak S.
        • Bach F.W.
        • Jensen T.S.
        • Sindrup S.H.
        Pain phenomena and possible mechanisms in patients with painful polyneuropathy.
        Pain. 2003; 101: 187-192
        • Pinney J.H.
        • Hawkins P.N.
        Amyloidosis.
        Ann Clin Biochem. 2012; 49: 229-241
        • Planté-Bordeneuve V.
        • Said G.
        Familial amyloid polyneuropathy.
        Lancet Neurol. 2011; 10: 1086-1097
        • Polydefkis M.
        • Allen R.P.
        • Hauer P.
        • Earley C.J.
        • Griffin J.W.
        • McArthur J.C.
        Subclinical sensory neuropathy in late-onset restless legs syndrome.
        Neurology. 2000; 55: 1115-1121
        • Salvi F.
        • Montagna P.
        • Plasmati R.
        • Rubboli G.
        • Cirignotta F.
        • Veilleux M.
        • Lugaresi E.
        • Tassinari C.A.
        Restless legs syndrome and nocturnal myoclonus: initial clinical manifestation of familial amyloid polyneuropathy.
        J Neurol Neurosurg Psychiatry. 1990; 53: 522-525
        • Sandkühler J.
        Models and mechanisms of hyperalgesia and allodynia.
        Physiol Rev. 2009; 89: 707-758
        • Sorensen L.
        • Molyneaux L.
        • Yue D.K.
        The level of small nerve fiber dysfunction does not predict pain in diabetic neuropathy: a study using quantitative sensory testing.
        Clin J Pain. 2006; 22: 261-265
        • Sorensen L.
        • Molyneaux L.
        • Yue D.K.
        The relationship among pain, sensory loss, and small nerve fibers in diabetes.
        Diabetes Care. 2006; 29: 883-887
        • Truini A.
        • Biasiotta A.
        • Di Stefano G.
        • La Cesa S.
        • Leone C.
        • Cartoni C.
        • Leonetti F.
        • Casato M.
        • Pergolini M.
        • Petrucci M.T.
        • Cruccu G.
        Peripheral nociceptor sensitization mediates allodynia in patients with distal symmetric polyneuropathy.
        J Neurol. 2013; 260: 761-766
        • Truini A.
        • Biasiotta A.
        • Di Stefano G.
        • Leone C.
        • La Cesa S.
        • Galosi E.
        • Piroso S.
        • Pepe A.
        • Giordano C.
        • Cruccu G.
        Does the epidermal nerve fibre density measured by skin biopsy in patients with peripheral neuropathies correlate with neuropathic pain?.
        Pain. 2014; 155: 828-832
        • Truini A.
        • Biasiotta A.
        • La Cesa S.
        • Di Stefano G.
        • Galeotti F.
        • Petrucci M.T.
        • Inghilleri M.
        • Cartoni C.
        • Pergolini M.
        • Cruccu G.
        Mechanisms of pain in distal symmetric polyneuropathy: a combined clinical and neurophysiological study.
        Pain. 2010; 150: 516-521
        • Truini A.
        • Garcia-Larrea L.
        • Cruccu G.
        Reappraising neuropathic pain in humans–how symptoms help disclose mechanisms.
        Nat Rev Neurol. 2013; 9: 572-582
        • Tsigos C.
        • White A.
        • Young R.J.
        Discrimination between painful and painless diabetic neuropathy based on testing of large somatic nerve and sympathetic nerve function.
        Diabet Med. 1992; 9: 359-365
        • Üçeyler N.
        • Zeller D.
        • Kahn A.K.
        • Kewenig S.
        • Kittel-Schneider S.
        • Schmid A.
        • Casanova-Molla J.
        • Reiners K.
        • Sommer C.
        Small fibre pathology in patients with fibromyalgia syndrome.
        Brain. 2013; 136: 1857-1867
        • van Hedel H.J.
        • Wirz M.
        • Dietz V.
        Assessing walking ability in subjects with spinal cord injury: validity and reliability of 3 walking tests.
        Arch Phys Med Rehabil. 2005; 86: 190-196
        • Veves A.
        • Young M.J.
        • Manes C.
        • Boulton A.J.
        Differences in peripheral and autonomic nerve function measurements in painful and painless neuropathy. A clinical study.
        Diabetes Care. 1994; 17: 1200-1202
        • Vrethem M.
        • Boivie J.
        • Arnqvist H.
        • Holmgren H.
        • Lindström T.
        Painful polyneuropathy in patients with and without diabetes: clinical, neurophysiologic, and quantitative sensory characteristics.
        Clin J Pain. 2002; 18: 122-127
        • Woolf C.J.
        Central sensitization: implications for the diagnosis and treatment of pain.
        Pain. 2011; 152: S2-S15
        • Yates J.W.
        • Chalmer B.
        • McKegney F.P.
        Evaluation of patients with advanced cancer using the Karnofsky performance status.
        Cancer. 1980; 45: 2220-2224