Characterization of Pain in Familial Amyloid Polyneuropathy.
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.


CONCLUSIONS
Pain in TTR-FAP includes several mechanisms varying with the course of the disease and the involvement of the different types of nerve fibers.
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.
Sophie
S
Ng Wing Tin
Réseau Amylose Henri-Mondor, Hôpital Henri Mondor, Créteil, France; Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Service de Neurologie, Créteil, France.
Violaine
V
Planté-Bordeneuve
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.
Hayet
H
Salhi
Université Paris Est Créteil, Faculté de Médecine, EA 4391, Créteil, France; Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Service de Neurochirurgie, Créteil, France.
Colette
C
Goujon
Réseau Amylose Henri-Mondor, Hôpital Henri Mondor, Créteil, France; Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Service de Cardiologie, Créteil, France.
Thibaud
T
Damy
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. Electronic address: jean-pascal.lefaucheur@hmn.aphp.fr.
Jean-Pascal
JP
Lefaucheur
D000328:Adult; D000368:Aged; D028227:Amyloid Neuropathies, Familial / Q000175:diagnosis* / Q000453:epidemiology / Q000503:physiopathology*; D000700:Analgesics / Q000627:therapeutic use; D003080:Cold Temperature; D018450:Disease Progression; D005071:Evoked Potentials; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000453:epidemiology / Q000503:physiopathology; D007834:Lasers; D008297:Male; D008875:Middle Aged; D009431:Neural Conduction / Q000502:physiology; D010146:Pain / Q000175:diagnosis* / Q000188:drug therapy / Q000453:epidemiology / Q000503:physiopathology*; D010147:Pain Measurement; D058748:Pain Perception; D017288:Pain Threshold; D010812:Physical Stimulation; D014110:Touch
D000700:Analgesics
Amyloidosis; laser evoked potentials; questionnaire; small fibers; thermal threshold