Neurofibromatosis type 1 (NF1) is the most common of a group of rare diseases known by the term, “Neurofibromatosis,” affecting 1 in 3000 to 4000 people. NF1 patients present with, among other disease complications, café au lait patches, skin fold freckling, Lisch nodules, orthopedic complications, cutaneous neurofibromas, malignant peripheral nerve sheath tumors, cognitive impairment, and chronic pain. Although NF1 patients inevitably express pain as a debilitating symptom of the disease, not much is known about its manifestation in the NF1 disease, with most current information coming from sporadic case reports. Although these reports indicate the existence of pain, the molecular signaling underlying this symptom remains underexplored, and thus, we include a synopsis of the literature surrounding NF1 pain studies in 3 animal models: mouse, rat, and miniswine. We also highlight unexplored areas of NF1 pain research. As therapy for NF1 pain remains in various clinical and preclinical stages, we present current treatments available for patients and highlight the importance of future therapeutic development. Equally important, NF1 pain is accompanied by psychological complications in comorbidities with sleep, gastrointestinal complications, and overall quality of life, lending to the importance of investigation into this understudied phenomenon of NF1. In this review, we dissect the presence of pain in NF1 in terms of psychological implication, anatomical presence, and discuss mechanisms underlying the onset and potentiation of NF1 pain to evaluate current therapies and propose implications for treatment of this severely understudied, but prevalent symptom of this rare disease.
Departments of aPharmacology and
bAnesthesiology, College of Medicine, The University of Arizona Health Sciences, Tucson, AZ, United States
cNeuroscience Graduate Interdisciplinary Program, College of Medicine, The University of Arizona Health Sciences, Tucson, AZ, United States
dThe Center for Innovation in Brain Sciences, The University of Arizona Health Sciences, Tucson, AZ, United States
Corresponding author. Address: Department of Pharmacology, College of Medicine, University of Arizona, 1501 North Campbell Dr, PO Box 245050, Tucson, AZ 85724, United States. Tel.: (520) 626-4281; fax: (520) 626-2204. E-mail address: email@example.com (R. Khanna).
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.painjournalonline.com).
Received August 29, 2018
Received in revised form November 12, 2018
Accepted November 20, 2018