Pain processing and pain assessment in Huntington's disease: Study protocol of the Huntington's disease - PAIN study

PLoS One. 2026 Apr 10;21(4):e0346039. doi: 10.1371/journal.pone.0346039. eCollection 2026.

ABSTRACT

BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative disease that causes motor (e.g., chorea) and non-motor symptoms (e.g., neurocognitive, neuropsychiatric and autonomic disturbances). Pain is a frequently reported non-motor symptom in HD, with a prevalence of around 40% in the manifest stage. Despite its high prevalence, patients with HD seem to be at risk for undertreatment of pain, as reflected by the lower analgesic use in HD in the advanced stages. The relatively low use of analgesics may result from under-recognition and inadequate assessment of pain, particularly in the advanced stages of HD. As HD progresses, pain recognition and assessment become increasingly challenging due to the emergence and progression of motor and neurocognitive symptoms. In contrast, the high prevalence of pain may be attributable to disturbances in the pain processing in terms of endogenous pain inhibition or pain facilitation. Despite the availability of specifically developed and internationally standardized experimental pain assessments to test psychometrics properties of observational pain scales and disturbances in pain processing, studies using these pain assessments in HD are too limited to permit definitive conclusions.

METHODS: A cross-sectional experimental study will be conducted in twenty genetically and clinically confirmed adult-onset HD patients. The primary aim is to assess the feasibility of the experimental design, which comprises three different standardized pain assessments, using a predefined feasibility checklist.

DISCUSSION: If feasibility is demonstrated, future studies using the comprehensive experimental design, including individually tailored experimental painful stimuli, are expected to provide insight into the psychometric properties of the Pain Assessment in Impaired Cognition scale (PAIC15) and the potential demonstration of altered pain processing in HD, supporting the development of improved pain management regimens. In particular, the motor symptoms (e.g., facial chorea) of HD may have an adverse impact on the psychometric properties of the PAIC15.

TRIAL REGISTRATION: Trial registration on ClinicalTrials.gov with number: NCT06693466. Medical Research Ethics Committee Leiden, The Hague and Delft registration number: P24.014.

PMID:41961860 | DOI:10.1371/journal.pone.0346039