Tehran University of Medical Sciences Archives of Anesthesiology and Critical Care 2423-5849 0 0 2026 10 24 1645 1645 Rahmat Noviandomo Department of Anesthesiology and Reanimation, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia. Anna Veterini Department of Anesthesiology and Reanimation, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia. & Department of Anesthesiology and Reanimation, Dr. Soetomo General Academic Hospital, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia. Kohar Santosa Department of Anesthesiology and Reanimation, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia. & Department of Anesthesiology and Reanimation, Dr. Soetomo General Academic Hospital, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia. Prananda Airlangga Department of Anesthesiology and Reanimation, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia. & Department of Anesthesiology and Reanimation, Dr. Soetomo General Academic Hospital, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia. Christrijogo Waloejo Department of Anesthesiology and Reanimation, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia. & Department of Anesthesiology and Reanimation, Dr. Soetomo General Academic Hospital, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia. 2026 05 25 2026 07 03 Background: Neuropathic pain is a refractory chronic pain condition driven in part by neuroinflammation. Interleukin-6 (IL-6) is a key pro-inflammatory mediator, and paracetamol monotherapy is often insufficient. Alkaloids of Mitragyna speciosa (kratom) have μ-opioid receptor agonist and anti-inflammatory activity, while nanoformulation may improve oral bioavailability. The objective is to evaluate the analgesic and anti-inflammatory effects of oral nano-kratom as an adjuvant to paracetamol on mechanical withdrawal threshold and serum IL-6 in a rat chronic constriction injury (CCI) model. Methods: A post-test-only randomized controlled animal study was conducted in 21 male Wistar rats assigned to vehicle control (K−), paracetamol 10 mg/kg (K1), or nano-kratom 30 mg/kg plus paracetamol 5 mg/kg (K2) (n = 7/group). After acclimatization, unilateral CCI of the left sciatic nerve was induced. Treatments were given orally once daily from day 7 to day 13, and endpoints were assessed on day 14. Mechanical withdrawal threshold was measured using von Frey filaments, and serum IL-6 was quantified by ELISA. One K− rat died before endpoint assessment; the final analyzed n = 6, 7, and 7. Results: Baseline von Frey thresholds were comparable across groups. CCI significantly reduced withdrawal thresholds in all groups. On day 14, thresholds differed significantly, with K2 showing the highest values, followed by K1 and K− (all pairwise p < 0.001). Serum IL-6 was lowest in K2; the difference was significant versus K− (p = 0.037) and approached significance versus K1 (p = 0.053). Conclusion: Nano-kratom combined with half-dose paracetamol produced greater antinociception than paracetamol alone and was associated with the lowest serum IL-6 levels. These findings support further evaluation of nano-formulated kratom as a multimodal adjuvant for neuropathic pain. https://aacc.tums.ac.ir/index.php/aacc/article/view/1645