“Painless palsy” revisited: a systematic review of pain in hereditary neuropathy with liability to pressure palsies

OBJECTIVES: Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) has long been described as a disorder of "painless palsies," shaping diagnostic and therapeutic paradigms. Increasing evidence suggests this characterization underestimates the true burden of pain in HNPP. METHODS: We systematically reviewed literature to examine how pain recognition and characterization in HNPP have evolved. MEDLINE, Embase, Web of Science, and CENTRAL were searched from database inception through August 2025 for studies explicitly reporting pain status. Data on pain prevalence, assessment methods, temporal trends, and associated clinical features were extracted. Studies were grouped into three eras reflecting diagnostic advances: early (≤1990; clinical diagnosis only), modern (1990-2015; introduction of genetic testing), and recent (≥2015; widespread use of genetic panels). RESULTS: Fifty-three studies comprising 655 patients met inclusion criteria. Reported pain prevalence increased over time, from reinforcing a "painless" paradigm in early studies to 34% in modern studies and 56% in recent studies. Recent studies more frequently identified complex neuropathic pain phenotypes. Only four studies (7.5%) used validated pain assessment tools, yet consistently reported higher prevalence and greater symptom complexity. CONCLUSION: HNPP is not uniformly painless. Pain is common, clinically relevant, and multifactorial, highlighting the need for standardized pain assessment to guide management.