Clinical Outcomes and Inflammatory Biomarker Changes After Intravenous Ketamine-Lidocaine Infusion in Refractory Neuropathic Pain: A Prospective Observational Pilot Study

Background: Refractory neuropathic pain remains difficult to manage despite multimodal pharmacotherapy.Intravenous ketamine and lidocaine act through distinct analgesic mechanisms, but prospective data on their combined use and on potential inflammatory biomarker changes remain limited.Objectives: The study aimed to evaluate changes in pain intensity and treatment tolerability following a single intravenous ketamine-lidocaine infusion in adults with refractory neuropathic pain and to explore the duration of perceived treatment effect, patient-reported functional outcomes, and changes in interleukin-6 (IL-6) and C-reactive protein (CRP).Methods: This prospective, single-center observational pilot study included 30 adults with refractory neuropathic pain.Participants received ketamine 15 mg plus lidocaine 4 mg/kg intravenously over 30 minutes while continuing their baseline pharmacotherapy.Pain intensity was assessed using a 0-10 numerical rating scale (NRS) at baseline, immediately after infusion, and at four-week follow-up.IL-6 and CRP were measured at baseline and four weeks.Changes in NRS scores were analyzed with the Friedman test followed by Holm-adjusted Wilcoxon signed-rank tests.Biomarker changes were assessed with paired tests selected according to the distribution of within-patient differences.Adverse events and exploratory patientreported outcomes were analyzed descriptively.Results: Mean NRS pain intensity decreased from 7.93 ± 1.64 at baseline to 4.93 ± 2.23 immediately after infusion and 5.63 ± 2.58 at four weeks (Friedman χ²(2) = 35.50,p <0.001).Reductions from baseline were significant both immediately after infusion (adjusted p <0.001; r = 0.82) and at four weeks (adjusted p <0.001; r = 0.80), whereas the difference between immediate and four-week scores was not significant (adjusted p = 0.077).A pain reduction of at least 30% was achieved by 76.7% of patients immediately after infusion and 53.3% at four weeks; reductions of at least 50% occurred in 36.7% and 30.0%, respectively.A perceived treatment effect lasting at least three weeks or still ongoing at the four-week follow-up was reported by 56.7% of participants.IL-6 decreased from 4.73 ± 2.89 pg/mL to 4.14 ± 2.84 pg/mL (p = 0.086) and CRP from 5.51 ± 3.63 mg/L to 4.69 ± 3.71 mg/L (p = 0.120); neither biomarker correlated significantly with pain intensity.Seventy percent of patients reported no spontaneous post-infusion symptoms, no hallucinations occurred, and no adverse event required premature discontinuation or additional medical intervention.Conclusions: A single ketamine-lidocaine infusion was followed by a reduction in self-reported pain that remained evident at four weeks in a proportion of patients, with predominantly mild and transient reported adverse effects.Because of the uncontrolled observational design, these changes cannot be attributed specifically to the pharmacological intervention, and the biomarker findings remain exploratory.Larger controlled studies with validated outcome measures and longer follow-up are needed to determine the efficacy and durability of this approach.