Gabapentin and Pregabalin Effects on Inflammation and Cardiac Function in Peripheral Neuropathic Pain

Peripheral neuropathic pain is a chronic condition associated with a lesion or disease of the somatosensory nervous system. Neuroimmune and inflammatory mechanisms may contribute to its development and persistence. Gabapentin and pregabalin are alpha-2-delta ligands commonly prescribed for neuropathic pain; however, whether these medications are associated with different short-term changes in inflammatory pathways and early cardiac function remains unclear.This is a single-center, prospective, controlled, observational cohort study with repeated measurements. A total of 75 adults will be enrolled in three groups: 25 patients with peripheral neuropathic pain who are prescribed gabapentin, 25 patients with peripheral neuropathic pain who are prescribed pregabalin, and 25 healthy controls without peripheral neuropathy or chronic neuropathic pain.The decision to initiate gabapentin or pregabalin, including the selected drug, starting dose, dose adjustment, continuation, or discontinuation, will be made by the treating neurosurgery physician as part of routine clinical care and independently of study participation. The investigators will not randomize participants, assign treatment, determine medication doses, or modify routine treatment decisions.Patients in the gabapentin and pregabalin cohorts will undergo baseline assessment before the first medication dose and a follow-up assessment 30 ± 7 days later. Healthy controls will undergo corresponding assessments at enrollment and after 30 ± 7 days. Clinical assessments will include demographic characteristics, neuropathic pain characteristics, pain severity measured using a 0-10 numerical rating scale, comorbidities, concomitant medications, blood pressure, heart rate, medication exposure, adherence, treatment tolerability, and adverse events.Routine laboratory findings will be recorded. No additional blood sample will be collected solely for research purposes. After completion of clinically required laboratory testing, leftover serum will be coded, aliquoted, stored at -80 °C, and used to measure the inflammatory and signaling biomarkers NLRP3, nuclear factor kappa B p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3), according to the manufacturers' instructions.Standard transthoracic echocardiography will be performed by a cardiologist at baseline and follow-up. Echocardiographic assessments will include left ventricular ejection fraction, left ventricular global longitudinal strain, left ventricular dimensions and wall thickness, left atrial volume index, transmitral E/A ratio, tissue Doppler e' velocity, E/e' ratio, tricuspid annular plane systolic excursion, right ventricular S' velocity, and other clinically relevant standard measurements.The primary objective is to compare changes from baseline to 30 ± 7 days in inflammatory biomarkers and subclinical cardiac function between the gabapentin and pregabalin cohorts. The primary analysis will assess the group-by-time interaction using a linear mixed-effects model. The healthy control cohort will serve as a reference group for secondary and exploratory comparisons. Additional analyses will examine associations among biomarker changes, pain severity, cardiac function, clinical characteristics, medication exposure, and treatment tolerability.De-identified clinical findings may also be integrated with publicly available, anonymous transcriptomic or genomic summary datasets for exploratory, hypothesis-generating translational analyses. No genomic sequencing will be performed on study participants, and biological samples will not be transferred outside the study institution.