Effect of Lactiplantibacillus plantarum in a model of formalin-induced inflammatory pain in rats
DOI:
https://doi.org/10.32776/revbiomed.v37.i2.1363Keywords:
Probiotics, Nociception, Acute pain, Animal modelsAbstract
Introduction: Inflammatory pain is a type of adaptive and protective pain caused by tissue damage or infection and mediated by the release of inflammatory factors. Several studies have shown that probiotics, especially those of the Lactobacillus genus, can reduce inflammatory and nociceptive factors, which are associated with pain relief.
Objective: To evaluate the antinociceptive effect of L. plantarum in a formalin-induced inflammatory pain model.
Methods: Female Wistar rats weighing between 180-200 g were used. The animals were divided into two groups (n=4 each): a vehicle group without treatment and a probiotic group treated with L. plantarum (1.5 × 10⁸ CFU/mL) orally for six months. At the end of the intervention, the formalin test was performed and the number of flinches of the injected limb was recorded over a 60-minute period . The AUC was then calculated and the groups were compared using Student's t-test.
Results: In phase 1, the group treated with L. plantarum showed a lower initial nociceptive response compared to the vehicle group, although this effect was not statistically significant. However, in phase 2, the group treated with the probiotic exhibited a consistently lower number of flinches over time, indicating an antinociceptive effect of L. plantarum.
Conclusions: These results support the hypothesis that L. plantarum could represent a promising therapeutic alternative that contributes to the management of acute inflammatory pain by acting through the gut-brain axis.
References
1. Raja SN, Carr DB, Cohen M, Finnerup NB, Flor H, Gibson S, et al. The revised International Association for the Study of Pain definition of pain: concepts, challenges, and compromises. Pain. 2020 Sep;161(9):1976-82. doi: 10.1097/j.pain.0000000000001939.
2. Afridi B, Khan H, Akkol EK, Aschner M. Pain Perception and Management: Where do We Stand? Curr Mol Pharmacol. 2021 Dec;14(5):678-88. doi: 10.2174/1874467213666200611142438.
3. Woolf CJ. What is this thing called pain? J Clin Invest. 2010 Nov;120(11):3742-4. doi: 10.1172/jci45178.
4. Souza Monteiro de Araujo D, Nassini R, Geppetti P, De Logu F. TRPA1 as a therapeutic target for nociceptive pain. Expert Opin Ther Targets. 2020 Oct;24(10):997-1008. doi: 10.1080/14728222.2020.1815191.
5. Zhang X, Zhu L, Wang X, Xia L, Zhang Y. Advances in the role and mechanism of miRNA in inflammatory pain. Biomed Pharmacother. 2023 May;161:114463. doi: 10.1016/j.biopha.2023.114463.
6. Shadnoush M, Nazemian V, Manaheji H, Zaringhalam J. The Effect of Orally Administered Probiotics on the Behavioral, Cellular, and Molecular Aspects of Adjuvant-Induced Arthritis. Basic Clin Neurosci. 2018 Sep;9(5):325-36. doi: 10.32598/bcn.9.5.325.
7. Yadav MK, Kumari I, Singh B, Sharma KK, Tiwari SK. Probiotics, prebiotics and synbiotics: Safe options for next-generation therapeutics. Appl Microbiol Biotechnol. 2022 Jan;106(2):505-21. doi: 10.1007/s00253-021-11646-8.
8. Rahman SO, Bariguian F, Mobasheri A. The Potential Role of Probiotics in the Management of Osteoarthritis Pain: Current Status and Future Prospects. Curr Rheumatol Rep. 2023 Dec;25(12):307-26. doi: 10.1007/s11926-023-01108-7.
9. Moyseos M, Michael J, Ferreira N, Sophocleous A. The Effect of Probiotics on the Management of Pain and Inflammation in Osteoarthritis: A Systematic Review and Meta-Analysis of Clinical Studies. Nutrients. 2024 Jul;16(14):2243. doi: 10.3390/nu16142243.
10. Martoni CJ, Srivastava S, Damholt A, Leyer GJ. Efficacy and dose response of Lactiplantibacillus plantarum in diarrhea-predominant irritable bowel syndrome. World J Gastroenterol. 2023 Jul;29(28):4451-65. doi: 10.3748/wjg.v29.i28.4451.
11. Un-Nisa A, Khan A, Zakria M, Siraj S, Ullah S, Tipu MK, et al. Updates on the Role of Probiotics against Different Health Issues: Focus on Lactobacillus. Int J Mol Sci. 2022 Dec;24(1):142. doi: 10.3390/ijms24010142.
12. Tjølsen A, Berge O-G, Hunskaar S, Rosland JH, Hole K. The formalin test: an evaluation of the method. Pain. 1992 Oct;51(1):5-17. doi: 10.1016/0304-3959(92)90003-t.
13. Zimmermann M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain. 1983 Jun;16(2):109-10. doi: 10.1016/0304-3959(83)90201-4.
14. López-Cano M, Fernández-Dueñas V, Llebaria A, Ciruela F. Formalin Murine Model of Pain. Bio Protoc. 2017 Dec;7(23):e2628. doi: 10.21769/BioProtoc.2628.
15. Abboud C, Duveau A, Bouali-Benazzouz R, Massé K, Mattar J, Brochoire L, et al. Animal models of pain: Diversity and benefits. J Neurosci Methods. 2021 Jan 15;348:108997. doi: 10.1016/j.jneumeth.2020.108997.
16. Ren H, Cao B, Xu Q, Zhao R, Li H, Wei B. Role of microbiota in pain: From bench to bedside. iMetaOmics. 2025 Feb;2(1):e58. doi: 10.1002/imo2.58.
17. Oh DK, Na HS, Jhun JY, Lee JS, Um IG, Lee SY, et al. Bifidobacterium longum BORI inhibits pain behavior and chondrocyte death, and attenuates osteoarthritis progression. PLoS One. 2023 Jun;18(6):e0286456. doi: 10.1371/journal.pone.0286456.
18. Amdekar S, Singh V. Studies on anti-inflammatory and analgesic properties of Lactobacillus rhamnosus in experimental animal models. J Complement Integr Med. 2016 Jun;13(2):145-50. doi: 10.1515/jcim-2015-0087.
19. Huang C-T, Wang L-K, Lue J-H, Chen S-H, Tsai Y-J. Lactobacillus Plantarum intake mitigates neuropathic pain behavior via enhancing macrophage M2 polarization in a rat model of peripheral neuropathy. Biomed Pharmacother. 2024 Jun;175:116769. doi: 10.1016/j.biopha.2024.116769
20. Wang X, Chen Y, Qian S, Kong J, Su Z, Wang Q, et al. Compound Probiotics Improve Neuropathic Pain Prognosis in a Murine Model of Chronic Constriction Injury. J Pain Res. 2024 Dec;17:4213-21. doi: 10.2147/JPR.S486259.
21. Chatsirisakul O, Leenabanchong N, Siripaopradit Y, Chang C-W, Buhngamongkol P, Pongpirul K. Strain-Specific Therapeutic Potential of Lactiplantibacillus plantarum: A Systematic Scoping Review. Nutrients. 2025 Mar;17(7):1165.
22. Lin YY, Wu CY, Tsai YS, Chen CC, Chang TC, Chen LC, et al. The joint protective function of live- and dead-Lactobacillus plantarum GKD7 on anterior cruciate ligament transection induces osteoarthritis. Aging (Albany NY). 2024 Sep;16(18):12559-73. doi: 10.18632/aging.206101.
23. Kaźmierczak-Siedlecka K, Daca A, Folwarski M, Witkowski JM, Bryl E, Makarewicz W. The role of Lactobacillus plantarum 299v in supporting treatment of selected diseases. Cent Eur J Immunol. 2021 Jan;45(4):488-93. doi: 10.5114/ceji.2020.101515.
24. Amaral FA, Sachs D, Costa VV, Fagundes CT, Cisalpino D, Cunha TM, et al. Commensal microbiota is fundamental for the development of inflammatory pain. Proc Natl Acad Sci USA. 2008 Feb;105(6):2193-7. doi: 10.1073/pnas.0711891105.
25. Mansuy-Aubert V, Ravussin Y. Short chain fatty acids: the messengers from down below. Front Neurosci. 2023 Jul;17:1197759. doi: 10.3389/fnins.2023.1197759.
26. Sashide Y, Takeda M. Gut microbiota-derived short-chain fatty acid suppresses the excitability of rat nociceptive secondary neurons via G-protein-coupled receptor 41 signaling. Mol Pain. 2025 Feb;21:17448069251320233. doi: 10.1177/17448069251320233.
27. Yang W, Yu T, Huang X, Bilotta AJ, Xu L, Lu Y, et al. Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL-22 production and gut immunity. Nat Commun. 2020 Sep;11(1):4457. doi: 10.1038/s41467-020-18262-6.
28. Laroute V, Beaufrand C, Gomes P, Nouaille S, Tondereau V, Daveran-Mingot ML, et al. Lactococcus lactis NCDO2118 exerts visceral antinociceptive properties in rat via GABA production in the gastro-intestinal tract. Elife. 2022 Jun;11:e77100. doi: 10.7554/eLife.77100.
29. Casertano M, Dekker M, Valentino V, De Filippis F, Fogliano V, Ercolini D. Gaba-producing lactobacilli boost cognitive reactivity to negative mood without improving cognitive performance: A human Double-Blind Placebo-Controlled Cross-Over study. Brain Behav Immun. 2024 Nov;122:256-65. doi: 10.1016/j.bbi.2024.08.029.
30. Zhong H-J, Wang S-Q, Zhang R-X, Zhuang Y-P, Li L, Yi S-Z, et al. Supplementation with high-GABA-producing Lactobacillus plantarum L5 ameliorates essential tremor triggered by decreased gut bacteria-derived GABA. Transl Neurodegener. 2023 Dec;12(1):58. doi: 10.1186/s40035-023-00391-9.
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Ana Victoria Estrada-Estrada, Crystell Guadalupe Guzmán-Priego, Guadalupe del Carmen Baeza-Flores, Karen Elvira García-Sánchez, Leova Pacheco-Gil
This work is licensed under a Creative Commons Attribution 4.0 International License.
Those authors who have publications with this magazine accept the following terms:
Authors will keep their copyright and guarantee the journal the right of first publication of their work, which will be simultaneously subject to the Creative Commons Recognition License that allows third parties to share the work whenever its author is indicated and his first publication in this magazine. The authors may adopt other non-exclusive licensing agreements for the distribution of the published version of the work (eg, deposit it in an institutional telematic file or publish it in a monographic volume) whenever the initial publication in this journal is indicated. Authors are allowed and advised to disseminate their work through the Internet (eg in institutional telematic archives or on their website) after the submission has been accepted and published, which can produce interesting exchanges and increase citations of the published work.
(See The effect of open access)
