145: TRPV1 Mediates Stress-induced Mechanical and Cold Hypersensitivity in Female Mice

Topic: Basic Science
Subtopic: Pain category (ICD-11), Chronic widespread pain, Developing methodology/technology, Drug Development, Behavioural studies, , , , , , , ,

Background and Aims: Chronic psychosocial distress is an etiological and aggravating factor of several chronic pain conditions including fibromyalgia characterized by chronic widespread musculoskeletal pain [1,2]. Although neuroinflammation is suggested to be involved in its background, the complex pathophysiological mechanisms remain unclear [2,3]. Transient Receptor Potential Vanilloid 1 (TRPV1) and Ankyrin 1 (TRPA1) are heat-, inflammation- and cold-sensing cation channels commonly co-localized on neurons medicating pain, but their roles in stress-related pain are unknown [4,5,6,7]. Therefore, we investigated their involvement in stress-induced pain models of mice related [8,9,10].

Methods: Female TRPV1 and TRPA1 knockout mice (TRPV1-/- and TRPA1-/-; 12–15-week-old, 22–26 g) were exposed to intermittent cold (ICS; alternating temperatures between 3 and 22°C for 3 days) or chronic restraint stress (CRS; 6 h immobilization/day for 14 days in well-ventilated tubes) [8,9,10]. Mechanical and cold sensitivities of the paws were measured using dynamic plantar aesthesiometer (DPA) and withdrawal latency from ice cold water, respectively [10,11]. Open Field Test (OFT) and Tail Suspension Test (TST) were performed to detect anxiety- and depression-like behaviors, thymus and adrenal weights were recorded to determine neuroendocrine alterations [11,12].

Results: Baseline mechanical and cold sensitivity values were similar in non-stressed TRPV1-/- and TRPA1-/- mice compared to their WTs. Both ICS and CRS induced approximately 17-25% mechanical and 40-70% cold hyperalgesia in WT mice, which were significantly smaller in TRPV1-/- but not TRPA1-/- mice. Cold hyperalgesia was transiently heightened in stressed TRPA1-/- on day 4 of the ICS model. Stress decreased immobility time in the TST and increased locomotor activity in the OFT in TRPV1-/- and TRPA1-/- animals. Both Stress conditions reduced thymus weight in WT mice, an effect significantly attenuated in TRPV1-/- but not TRPA1-/- mice, while adrenal weight increased.

Conclusions: TRPV1, but not TRPA1, mediates chronic stress-induced pain responses, but both are involved in anxiety-related hyperlocomotion and depression-like behaviors. These data suggest that TRPV1 might be a novel target for chronic stress-related chronic pain conditions like FM.

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Presenting Author: Bani Ata Mohammad Izzeldeen Ali
Submitting Author: Mohammad Bani Ata

Senior Author: Tékus Valéria

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• Kepe Eszter - University of Pécs, Medical School, Department of Pharmacology and Pharmacotherapy, Pécs, Hungary
• Éva Borbély - University of Pécs, Medical School, Department of Pharmacology and Pharmacotherapy, Pécs, Hungary
• Helyes Zsuzsanna: Professor in Pharmacology - University of Pécs, Medical School, Department of Pharmacology and Pharmacotherapy, Pécs, Hungary, PharmInVivo Ltd., Pécs, Hungary, Hungarian Research Network-University of Pécs, Chronic Pain Research Group, Hungary, National Laboratory for Drug Research and Development, Budapest, Hungary