Prolonged Sinus Pauses Revealing A Paroxysmal Extreme Pain Disorder: Is It A Frequent Situation?


  • Sahar Mouram Faculty of Medicine and Pharmacy, Rabat, Morocco
  • Hicham Sabor Faculty of Medicine and Pharmacy, Rabat, Morocco
  • Ibtissam Fellat Faculty of Medicine and Pharmacy, Rabat, Morocco



Paroxysmal extreme pain disorder- sinus pauses- anesthetic risk- pacemaker.


Title :Paroxysmal extreme pain disorder (PEPD) is an autosomal dominant painful neuropathy with many,but not all, cases linked to gain-of-function mutations in SCN9A which encodes voltage-gated sodium channel Na.1.7. It is a very rare condition featured by flushing of the lower half of the body and excruciating burning pain caused by any stimulus below the waist or in the perianal region. PEPD may be associated with cardiovascular instability, especially prolonged sinus pauses, and thus has anesthetic implications. Pacemaker implantation is the alternative therapeutic option, but its indications have not been clarified yet.

Background: This condition is well described in neurological literature, but to our knowledge, this is the first case report of a patient with paroxysmal extreme pain disorder with prolonged sinus pauses requiring anesthesia for an epicardial pacemaker even with the peri-operative risk of the pathology.This clinical observation can help for a better management and understanding of the cardiac risk complications of PEPD especially for an infant whose diagnostic is frequently made at the stage of complication This clinical observation can put the item on the necessity of establishing recommendations for management of cardiac complications during PEPD.

Case report: We extensively searched the literature on cardiac pacing in patients with PEPD and we described a new case of a 9 month old infant who was admitted in the emergency department for an episode of malaise apnea and hemifacial cyanosis relevant to PEPD. The neurologic exploration was normal. The diagnostic was confirmed by genetic study. The 24 hours recording demonstrated long pauses of 15 seconds during the crisis justifying the implantation of epicardial pacemaker without peri-operatory complications due to the high anesthetic risk of this pathology.

Conclusion: Paroxysmal extreme pain disorder is a highly distinctive sodium channelopathy with incompletely carbamazepine-sensitive bouts of pain and sympathetic nervous system dysfunction. It is most likely to be misdiagnosed as epilepsy and, particularly in infancy, as hyperekplexia and reflex anoxic seizures. Clinicians must evocate this diagnostic even any clinical suspicion given the severity of  cardiac complications.

Author Biographies

Sahar Mouram, Faculty of Medicine and Pharmacy, Rabat, Morocco

Cardiology B Department

Hicham Sabor, Faculty of Medicine and Pharmacy, Rabat, Morocco

Cardiology Department, Military Hospital

Ibtissam Fellat, Faculty of Medicine and Pharmacy, Rabat, Morocco

Cardiology B  Department


-Estacion M , Dib-Hajj SD , Benke PJ, Rene HM , Morsche TE ,Eastman EM , Macala LJ and al . NaV1.7 Gain-of-Function Mutations as a Continuum: A1632E Displays Physiological Changes Associated with Erythromelalgia and Paroxysmal Extreme Pain Disorder Mutations and Produces Symptoms of Both Disorders. The Journal of Neuroscience, 22 October 2008, 28(43): 11079-11088.

- Dib-Hajj SD , Estacion M , Jarecki BW , Tyrrell L , Fischer TZ , Lawden M et al . Paroxysmal extreme pain disorder M1627K mutation in human Nav1.7 renders DRG neurons hyperexcitable. Molecular Pain 2008, 4(37) :1-14.

Theile JW, Brian W, Jarecki AD, Heodore RT . Cummins.Nav1.7 mutations associated with paroxysmal extreme pain disorder, but not erythromelalgia, enhance Navβ4 peptide-mediated resurgent sodium currents. The Journal of Physiology. 589(3) : 597–608.

- Caffrey JM , Eng DL, Black JA , Waxman SG, Kocsis JD . Three types of sodium channels in adult rat dorsal root ganglion neurons. Brain Res. 1992; 592(1–2):283–297.

-Hayden R , Grossman M . Rectal ocular, and submaxillary pain; a familial autonomic disorder related to proctalgia fugaz: report of a family.AMA J 1959; 97: 479–82.

- Fertleman CR , Ferrie CD, Aicardi J, Bednarek NA, Eeg-Olofsson O, Elmslieand FV et al. Paroxysmal extreme pain disorder (previously familial rectal pain syndrome). Neurology 2007; 69: 586–95.


-Fertleman CR, Baker MD, Parker KA, et al. SCN9A mutations in paroxysmal extreme pain disorder: allelic variants underlie distinct channel defects and phenotypes. Neuron 2006; 52: 767–74.

-Choi JS, Waxman SG. Physiological interactions between Nav1.7 and Nav1.8 sodium channels: a computer simulation study. J Neurophysiol 2011; 106: 3173–84.

-Lavin MM. , Solano C. Dorsal root ganglia, sodium channels, and fibromyalgia sympathetic pain. Medical Hypotheses. 2009 ;72 : 64–66 .

- Emery EC , Habib AM ,Cox JJ , Nicholas AK , Gribble FM ,Woods CG ,Reimann F . Novel SCN9A Mutations Underlying Extreme Pain Phenotypes: Unexpected Electrophysiological and Clinical Phenotype Correlations. The Journal of Neuroscience.2015 ; 35(20):7674 –7681 .

- Dugan RE. Familial rectal pain. Lancet 1972; 1: 854 ;

-Black JA, Dibb-Hajj S, McNabola K, Jeste S, Rizzo MA, Kocsis JD, Waxman SG. Spinal sensory neurons express multiple sodium channel alpha subunit mRNAs. Mol Brain Res 1996;43:117–31;

-Harrison CM, Goddard JM, Rittey CD. The use of regional anaesthetic blockade in a child with recurrent erythromelalgia. Arch Dis Child 2003;88:65–6.

Brar HBK, El-Dabe S, Shehade S. Treatment of refractory primary erythromelalgia in a child using a continuous epidural infusion. Pain Clin 2002;12:65–9.

- Nassar MA, Levato A, Stirling LC, Wood JN. Neuropathic pain develops normally in mice lacking both Nav1.7 and Nav1.8. Mol Pain 2005;1:24.

- Darbar A ,Bilolikar A .Anesthesia for a Patient with Paroxysmal Extreme Pain Disorder.

-- Gould HJ III, Engl JD, Soignier RD, Nolan P, Minor LD, Liu ZP et al . Ibuprofen blocks changes in Nav1.7 and 1.8 sodium channels associated with complete Freund’s adjuvant-induced inflammation in rat. Pain 2004;5:270–80.