Fasakin OW, Awosika A, Ojo FM, Boboye AS. Effects of Kalanchoe pinnata, exercise, and stimulation on neuroinflammation, redox homeostasis, and neuropathic pain in a Wistar-rat model. World J Exp Med 2026; 16(3): 124614 [DOI: 10.5493/wjem.124614]
Corresponding Author of This Article
Ayoola Awosika, MD, Department of Family and Community Medicine, University of Illinois College of Medicine Peoria, 1 Illini Drive, Bloomington, IL 61601, United States. ayoolaawosika@yahoo.com
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Fasakin OW, Awosika A, Ojo FM, Boboye AS. Effects of Kalanchoe pinnata, exercise, and stimulation on neuroinflammation, redox homeostasis, and neuropathic pain in a Wistar-rat model. World J Exp Med 2026; 16(3): 124614 [DOI: 10.5493/wjem.124614]
World J Exp Med. Sep 20, 2026; 16(3): 124614 Published online Sep 20, 2026. doi: 10.5493/wjem.124614
Effects of Kalanchoe pinnata, exercise, and stimulation on neuroinflammation, redox homeostasis, and neuropathic pain in a Wistar-rat model
Olamide Wilson Fasakin, Ayoola Awosika, Funmilayo Mercy Ojo, Ayodeji Samuel Boboye
Olamide Wilson Fasakin, Funmilayo Mercy Ojo, Department of Medical Biochemistry, School of Basic Medical Sciences, College of Medicine, Federal University of Technology, Akure 234034, Nigeria
Ayoola Awosika, Department of Family and Community Medicine, University of Illinois College of Medicine Peoria, Bloomington, IL 61601, United States
Ayodeji Samuel Boboye, Department of Biological Sciences, Institute of Exact and Biological Sciences, Federal University of Ouro Preto, Minas Novas 010000, Minas Gerais, Brazil
Author contributions: Fasakin OW, Awosika A, Ojo OM, and Boboye AS conceived and designed the experiments, performed them, analyzed and interpreted the data, provided reagents, materials, analysis tools, or data, wrote the manuscript, and reviewed the final version.
AI contribution statement: Grammarly (v1.2.283.1934) was used to improve English proficiency.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Animal Ethics Committee at the Center for Research and Development, Federal University of Technology, Akure, with Ethical approval (No. FUTA/ETH/25/471).
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: All data generated or analyzed during this study are included in this published article and its Supplementary material. No additional data are available.
Corresponding author: Ayoola Awosika, MD, Department of Family and Community Medicine, University of Illinois College of Medicine Peoria, 1 Illini Drive, Bloomington, IL 61601, United States. ayoolaawosika@yahoo.com
Received: June 23, 2026 Revised: August 4, 2026 Accepted: September 17, 2026 Published online: September 20, 2026 Processing time: 92 Days and 21.9 Hours
Abstract
BACKGROUND
Neuropathic pain is a persistent, treatment-resistant condition driven not only by peripheral nerve injury but also by maladaptive neuroplasticity in central pain-regulatory networks. Evidence increasingly points to dysfunction in the prefrontal cortex (PFC), a vital area for top-down control of pain, emotions, and autonomic functions, as a key factor in maintaining pain hypersensitivity.
AIM
To examine the combined effects of Kalanchoe pinnata (KP), treadmill exercise, and vagus nerve stimulation (VNS) on neuroinflammation, redox homeostasis, and neuropathic pain in a rat model.
METHODS
Neuropathic pain was induced via partial sciatic nerve ligation. KP was administered orally at an effective dose of 100 mg/kg. Rats were assigned to 7 groups: (1) Sham; (2) Partial sciatic nerve ligation-neuropathic pain-induced; (3) Gabapentin; (4) KP alone; (5) KP + exercise; (6) KP + VNS; and (7) KP + exercise + VNS. Pain behaviors were assessed using mechanical allodynia and thermal hyperalgesia tests. Biochemical analysis of the PFC measured oxidative stress markers, pro-inflammatory cytokines [nuclear factor-kappa B, tumor necrosis factor alpha, interleukin (IL)-1β, IL-6], anti-inflammatory cytokine (IL-10), nitric oxide, monoaminergic and cholinergic biomarkers. Molecular analysis measured nuclear factor erythroid 2-related factor 2, heme-oxygenase 1, Kelch-like ECH-associated protein 1, B-cell lymphoma 2 associated X-protein, B-cell lymphoma 2, caspase-3, brain-derived neurotrophic factor, and cAMP response element-binding protein in the PFC.
RESULTS
Results showed that treatments significantly (P < 0.05) reduced pain behaviors compared to untreated controls. Treatments also significantly (P < 0.05) decreased lipid peroxidation, lowered pro-inflammatory cytokine levels, increased antioxidant activity, and restored the balance between neuronal and apoptotic processes. The combination therapies produced greater biochemical normalization than KP monotherapy, suggesting enhanced therapeutic responses through multimodal intervention. The triple treatment produced the most notable effects, significantly normalizing multiple inflammatory and redox parameters.
CONCLUSION
KP alleviated neuropathic pain, and the enhancement with exercise and VNS highlights the potential of multimodal strategies targeting cortical pain-control networks. This therapeutic approach demonstrates potential as a multimodal preclinical strategy for neuropathic pain management and warrants further investigation.
Core Tip: Neuropathic pain is a persistent, treatment-resistant condition driven not only by peripheral nerve injury but also by maladaptive neuroplasticity in central pain-regulatory networks. Evidence increasingly points to dysfunction in the prefrontal cortex, a vital area for top-down control of pain, emotions, and autonomic functions, as a key factor in maintaining pain hypersensitivity. This study examined the combined effects of Kalanchoe pinnata, treadmill exercise, and vagus nerve stimulation on neuroinflammation, redox homeostasis, and neuropathic pain in a rat model. This study shows that combining Kalanchoe pinnata, treadmill exercise, and vagus nerve stimulation offers better relief for neuropathic pain than any single treatment or drug. This triple therapy activates the nuclear factor erythroid 2-related factor 2/heme-oxygenase 1 pathway, reduces neuroinflammation, restores neuroplasticity, decreases cell death, and normalizes neurotransmission by correcting molecular imbalances in the prefrontal cortex.
