Ventral posterior nucleus volume is associated with neuropathic pain intensity in neuromyelitis optica spectrum disorders

Background: Neuropathic pain (NP) is frequent in neuromyelitis optica spectrum disorders (NMOSD). The ventral posterior nucleus (VPN) of the thalamus receives sensory afferences from the spinothalamic tracts and is associated with central pain in other conditions. Objective: To investigate associations between NP and VPN volume in aquaporin-4-IgGpositive (AQP4-IgG+) NMOSD. Methods: This cross-sectional study included 32 AQP4-IgG+ NMOSD patients and 37 healthy controls. NP intensity was determined by the PainDetect Questionnaire. Spinal cord lesion number and location as well as VPN volume were assessed by MRI, the latter using a multi-atlas-based automated segmentation. Results: Twenty-five patients (78%) suffered from NP and seven had no pain. Mean VPN volume did not differ between patients with and without NP (p=0.533) or between patients and controls. However, mean VPN volume correlated with average (rho=-0.486, p=0.019) and worst pain intensity (rho=-0.593, p=0.003). Of note, no other thalamic nuclei volumes correlated with measures of pain intensity. Compared to pain-free patients, patients with NP had more lesions involving the thoracic spinal cord (p=0.007). The relationships between VPN and pain intensity measures remained after adjustment for age, myelitis count, and spinal cord lesion location. Conclusion: Our data support a model where thoracic spinal cord lesions are associated with the development of NP in AQP4-IgG+ NMOSD and the VPN plays a role in the modulation of NP intensity. VPN volume as assessed in our study may be a clinically meaningful imaging marker of pain severity in AQP4-IgG+ NMOSD.