77: Reduced TET1 in the DRG and spinal cord is necessary for sleep disturbance to prolong surgical pain

Topic: Basic Science
Subtopic: Pain category (ICD-11), Chronic postsurgical pain, , , , , , , , Genetics and Epigenetics,

Background and Aims: Sleep disturbance delays surgical pain recovery. This impact is associated with the dysregulation of gene expression in the dorsal root ganglion (DRG) and spinal dorsal horn (SDH). However, the mechanisms underlying this dysregulation remain unclear.

Methods: The level of TET1 was examined in the DRG and SDH following plantar incision in rats subjected to short-term rapid eye movement sleep disturbance (REMSD). HSV-TET1 was microinjected into the ipsilateral L4/5 DRGs or SDH, and its effects on μ-opioid receptor (MOR) expression, TET1 binding to the Oprm1 promoter, and promoter-associated 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) levels in both microinjected regions were assessed. Nociceptive hypersensitivity was evaluated in these rats. Additionally, the effect of Tet1 siRNA microinjection, with or without LV-MOR, on MOR expression in microinjected DRGs and SDH and nociceptive threshold in naïve rats was assessed.

Results: REMSD downregulated TET1 in the ipsilateral L4/5 DRGs and SDH and exacerbated/prolonged incisional pain. HSV-TET1 microinjection restored MOR expression, TET1 binding activity to Oprm1 promoter, and 5hmC levels at the promoter while reducing 5mC accumulation in microinjected L4/5 DRGs or SDH and prevented REMSD-induced prolongation of incisional pain. Conversely, Tet1 siRNA microinjection reduced MOR expression in microinjected L4/5 DRGs or SDH and induced mechanical heat and cold hypersensitivity, effects abolished by LV-MOR co-microinjection.

Conclusions: TET1 downregulation is required for short-term sleep disturbance to delay surgical pain recovery, likely by reducing MOR expression in the DRG and SDH.

References: Wang, P. K.; Cao, J.; Wang, H.; Liang, L.; Zhang, J.; Lutz, B. M.; Shieh, K. R.; Bekker, A.; Tao, Y. X. Short-Term Sleep Disturbance-Induced Stress Does not Affect Basal Pain Perception, but Does Delay Postsurgical Pain Recovery. J. Pain 2015, 16 (11), 1186-1199.
Cao, J.; Wang, P. K.; Tiwari, V.; Liang, L.; Lutz, B. M.; Shieh, K. R.; Zang, W. D.; Kaufman, A. G.; Bekker, A.; Gao, X. Q.; et al. Short-term pre- and post-operative stress prolongs incision-induced pain hypersensitivity without changing basal pain perception. Mol. Pain 2015, 11 (1), 73.

Presenting Author: Yuan-Xiang Tao
Submitting Author: Yuan-Xiang Tao

Senior Author: Yuan-Xiang Tao

IASP 2026 Global Year theme of Neuropathic Pain: No

• Jing Cao: PhD - New Jersey Medical School, Rutgers, The State University of New Jersey
• Po-Kai Wang: PhD, MD - New Jersey Medical School, Rutgers, The State University of New Jersey
• Bo Xu: PhD, MD - New Jersey Medical School, Rutgers, The State University of New Jersey
• Xiyao Gu: PhD - New Jersey Medical School, Rutgers, The State University of New Jersey
• Zhiqiang Pan: PhD - New Jersey Medical School, Rutgers, The State University of New Jersey
• Weihua Cai: PhD - New Jersey Medical School, Rutgers, The State University of New Jersey
• Huijuan Hu: PhD - New Jersey Medical School, Rutgers, The State University of New Jersey
• Yuan-Xiang Tao: PhD, MD - New Jersey Medical School, Rutgers, The State University of New Jersey