Protein disulfide isomerase modulation of TRPV1 controls heat hyperalgesia in chronic pain
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Updated: Sep 27, 2025

Chronic Post-Ischemia Pain Model for Complex Regional Pain Syndrome Type-I in Rats
Published on: January 21, 2020
Yongxue Zhang1, Qi Miao2, Sai Shi3
1Department of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei, China; Department of Pharmacy, The First Hospital of Handan, Handan, Hebei, China.
Abstract:
Protein disulfide isomerase (PDI) plays a key role in maintaining cellular homeostasis by mediating protein folding via catalyzing disulfide bond formation, breakage, and rearrangement in the endoplasmic reticulum. Increasing evidence suggests that PDI can be a potential treatment target for several diseases. However, the function of PDI in the peripheral sensory nervous system is unclear. Here we report the expression and secretion of PDI from primary sensory neurons is upregulated in inflammatory and neuropathic pain models. Deletion of PDI in nociceptive DRG neurons results in a reduction in inflammatory and neuropathic heat hyperalgesia. We demonstrate that secreted PDI activates TRPV1 channels through oxidative modification of extracellular cysteines of the channel, indicating that PDI acts as an unconventional positive modulator of TRPV1. These findings suggest that PDI in primary sensory neurons plays an important role in development of heat hyperalgesia and can be a potential therapeutic target for chronic pain.
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