147: T and B lymphocytes mediate chronic immobilization-induced pain responses in male mice
Topic: Basic Science
Subtopic: Pain category (ICD-11), Chronic widespread pain, Assessment and Measurement of Pain/Nociception, Transgenic models, Behavioural studies, , , , , , , ,
Background and Aims: Chronic stress induces and aggravates many chronic pain conditions, such as widespread musculoskeletal pain in fibromyalgia, but the pathophysiological mechanisms are not fully understood. Autoimmunity and neuroimmune interactions have been considered as primary causes, where T and B lymphocytes play key roles. Therefore, the involvement of these cells in chronic stress-induced pain, anxiety and depression-like behaviour was investigated using lymphocyte-deficient mice.
Methods: Chronic restrain stress (CRS; 6 hours/day for 14 days) was performed on recombination activator gene deficient (Rag1-/-) mice on both sexes compared to their C57/Bl6 wild-type (WT) controls (10-12 weeks old, 18-28 g). Touch sensitivity of the paws was measured by dynamic plantar esthesiometry, cold sensitivity by detecting withdrawal latency from icy water. Open field test (OFT), light-dark box (LDB) and tail suspension test (TST) were performed after the stress, thymus and adrenal glands weights were detected at the end of the experiment.
Results: Without stress, no difference was found in Rag1-/- mice compared to their WTs in all examined parameters. CRS caused 60-70% and 40-50% decrease in mechanical and cold sensitivity in WT males and females, but his mechanical hyperalgesia was significantly lower in male Rag1-/- animals. Stress decreased the time spent in the middle zone of the OFT and the light of the LDB and time spent immobility in TST with no effect of gene deletion. The thymus weights of non-stressed Rag1-/- mice were significantly lower than those of WTs, and stress further reduced thymus weight in all groups.
Conclusions: These results suggests, that T and B lymphocytes might have a crucial role in chronic immobilization-induced mechanical pain responses in male mice.
References: Brum ES, Becker G, Fialho MFP, Oliveira SM (2022). Animal models of fibromyalgia: What is the best choice? Pharmacol. Therap. 2022;230:1077959. doi: 10.1016/j.pharmthera.2021.107959.
Borbély, É., Kecskés, A., Kun, J., Kepe, E., Fülöp, B., Kovács-Rozmer, K., Scheich, B., Renner, É., Palkovits, M., & Helyes, Z. (2023). Hemokinin-1 is a mediator of chronic restraint stress-induced pain. Scientific reports, 13(1), 20030. https://doi.org/10.1038/s41598-023-46402-7
Fülöp, B., Hunyady, Á., Bencze, N., Kormos, V., Szentes, N., Dénes, Á., Lénárt, N., Borbély, É., & Helyes, Z. (2023). IL-1 Mediates Chronic Stress-Induced Hyperalgesia Accompanied by Microglia and Astroglia Morphological Changes in Pain-Related Brain Regions in Mice. International journal of molecular sciences, 24(6), 5479. https://doi.org/10.3390/ijms24065479
Goebel A, et al. (2022). The autoimmune aetiology of unexplained chronic pain. Autoimmun. Rev. 2022;21:103015. doi: 10.1016/j.autrev.2021.103015.
Himanshu, Dharmila; Deepa Sarkar; Nutan. A Review of Behavioral Tests to Evaluate Different Types of Anxiety and Anti-anxiety Effects. Clin Psychopharmacol Neurosci. 2020 Aug 31;18(3):341-351. doi: 10.9758/cpn.2020.18.3.341.
Mashaghi A, et al. (2016). Neuropeptide substance P and the immune response. Cell. Mol. Life Sci. 2016;73:4249–4264. doi: 10.1007/s00018-016-2293-z.
N K Popova, M A Tibeikina (2010). Immobility and hyperthermia in the tail suspension test: association with the Porsolt test and the reflex startle reaction in 11 inbred mouse strains and the effects of genetic knockout of MAO A. Neurosci Behav Physiol. 2010 Jun;40(5):489-94. DOI: 10.1007/s11055-010-9286-4
Scheich, B., Vincze, P., Szőke, É., Borbély, É., Hunyady, Á., Szolcsányi, J., Dénes, Á., Környei, Z., Gaszner, B., & Helyes, Z. (2017). Chronic stress-induced mechanical hyperalgesia is controlled by capsaicin-sensitive neurones in the mouse. European journal of pain (London, England), 21(8), 1417–1431. https://doi.org/10.1002/ejp.1043
Sergio Gutierrez Nunez, Sara Peixoto Rabelo, Nikola Subotic, James Wilson Caruso, Nebojsa Nick Knezevic (2025). Chronic Stress and Autoimmunity: The Role of HPA Axis and Cortisol Dysregulation, Int J Mol Sci. 2025 Oct 14;26(20):9994. doi: 10.3390/ijms26209994.
Fundings: HUN-REN-PTE (Chronic Pain Research Group), Pécs, National Brain Research Program 3.0, NKFIH FK_146283, OTKA K138046, TKP2021-EGA-16
Presenting Author: Eszter Kepe
Submitting Author: Eszter Kepe
Senior Author: Valéria Tékus
IASP 2026 Global Year theme of Neuropathic Pain: Yes
Co-Authors:
- Barbara Fülöp: Dr. - 1. Institute of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, 2.National Laboratory for Drug Research and Development, Magyar tudósok krt. 2. H-1117 Budapest, Hungary 3.HUN-REN-PTE, Chronic Pain Research Group, Pécs, Hungary
- Éva Borbély: Dr. - 1. Institute of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, 2.National Laboratory for Drug Research and Development, Magyar tudósok krt. 2. H-1117 Budapest, Hungary 3.HUN-REN-PTE, Chronic Pain Research Group, Pécs, Hungary
- Péter Balogh: Prof. Dr. - Department of Immunology and Biotechnology, Clinical Center, University of Pécs, Pécs Hungary
- Zsuzsanna Helyes: Prof. Dr. - 1. Institute of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, 2.National Laboratory for Drug Research and Development, Magyar tudósok krt. 2. H-1117 Budapest, Hungary 3.HUN-REN-PTE, Chronic Pain Research Group, Pécs, Hungary, 5. PharmInVivo Kft., Pécs, Hungary
- Valéria Tékus: Dr. - 1. Institute of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, 3.HUN-REN-PTE, Chronic Pain Research Group, Pécs, Hungary, 5. PharmInVivo Kft., Pécs, Hungary
T and B lymphocytes mediate chronic immobilization-induced pain responses in male mice
Category
Poster
Description
Session Type: Posters
Room: Exhibit Hall EH102-103
28/10/2026
03:15 PM - 04:45 PM