Pain Relief Reverses Hippocampal Abnormalities in Trigeminal Neuralgia

•The hippocampus is bilaterally smaller in trigeminal neuralgia (TN) patients.•In patients who had pain relief, hippocampal abnormalities were normalized.•Hippocampal changes are driven by CA2/3, CA4, dentate gyrus and hippocampal proper.•Females show a more significant change compared to males.•TN provides a unique opportunity to study hippocampal changes after pain relief. Chronic pain patients frequently report memory and concentration difficulties. Objective testing in this population points to poor performance on memory and cognitive tests, and increased comorbid anxiety and depression. Recent evidence has suggested convergence between chronic pain and memory deficits onto the hippocampus. The hippocampus consists of heterogenous subfields involved in memory consolidation, behavior regulation, and stress modulation. Despite significant studies outlining hippocampal changes in human and chronic pain animal models, the effect of pain relief on hippocampal abnormalities remains unknown. Trigeminal neuralgia (TN) is a chronic neuropathic pain disorder which is highly amenable to surgical interventions, providing a unique opportunity to investigate the effect of pain relief. This study investigates the effect of pain relief on hippocampal subfields in TN. Anatomical MR images of 61 TN patients were examined before and 6 months after surgery. Treatment responders (n = 47) reported 95% pain relief, whereas non-responders (n = 14) reported 40% change in pain on average. At baseline, patients had smaller hippocampal volumes, compared to controls. After surgery, responders’ hippocampal volumes normalized, largely driven by CA2/3, CA4, and dentate gyrus, which are involved in memory consolidation and neurogenesis. We propose that hippocampal atrophy in TN is pain-driven and successful treatment normalizes such abnormalities. Chronic pain patients have structural abnormalities in the hippocampus and its subfields. Pain relief normalizes these structural abnormalities and impacts patients in a sex-dependent manner. [Display omitted]