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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Article info
Publication history
Published online: August 17, 2015
Accepted:
July 14,
2015
Received in revised form:
June 14,
2015
Received:
March 30,
2015
Footnotes
The authors declare no conflict of interest related to this study.
Identification
Copyright
© 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.
