Different Pain States of Trigeminal Neuralgia Make Significant Changes in the Plasma Proteome and Some Biochemical Parameters: a Preliminary Cohort Study

Trigeminal neuralgia (TN) with chronic and severe neuropathic pain leads to remarkable interference in daily living activities of patients. Unknown molecular mechanisms involved in TN pathophysiology are a challenge for complete treatment of the disease. The present study was conducted to investigate changes in the plasma proteome beside biochemical parameters, including calcitonin gene-related peptide (CGRP), nitric oxide (NO), amino acids, and vitamin D (Vit D) in different pain states in TN patients. Plasma samples were obtained from the control group (#13) and patients with purely paroxysmal type of classical TN (#13) before and after microvascular decompression (MVD). We analyzed plasma proteome using two-dimensional gel electrophoresis (2-DE) and identified altered proteins by applying MALDI-TOF/TOF mass spectrometry. The plasma levels of neurotransmitters (CGRP, NO, and amino acids) and Vit D were investigated by ELISA and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pain-rating index (PRI) was specified using a McGill pain questionnaire, which indicated a significant pain reduction after MVD. Plasma proteome analysis showed upregulated expression of transthyretin (TTR), retinol-binding protein 4 (RBP4), and alpha-1-acid glycoprotein 2 (AGP2) in TN patients compared to control group; whereas, TTR and RBP expression was downregulated after surgery. Moreover, the elevated NO and CGRP and decreased Vit D concentrations were observed in patients. After surgery, NO, Arg, Cit, and Gly levels were decreased along with pain relief. Our findings support the role of altered proteins in TN pathophysiology and suggest involvement of the evaluated neurotransmitters and Vit D in pain pathway sensitization during the disease.