Cellular senescence in chronic pain: Mechanisms and senotherapeutic perspectives
Abstract
Chronic pain often persists after the initial injury, inflammation, or tissue stress has subsided, suggesting that sustained cellular and microenvironmental changes contribute to pain chronification. Cellular senescence may be one of the mechanisms linking persistent tissue stress with neuroinflammation and altered pain processing. Senescence or senescence-like changes have been reported in nociceptors, dorsal root ganglion neurons, glial cells, immune cells, and local tissue-resident cells in several chronic pain conditions. These changes may influence pain through senescence-associated secretory phenotype (SASP)-related signaling, which can sustain inflammation, increase nociceptor excitability, promote glial activation, and contribute to peripheral and central sensitization. The available evidence, however, is not equally strong across pain conditions. Neuropathic pain and some degenerative nociceptive pain models provide relatively direct evidence, including senescence-related phenotypes and improvement after senolytic treatment. In nociplastic pain, glial and neuroimmune changes overlap with mechanisms associated with senescence, but direct evidence of cellular senescence remains limited. Evidence in bone cancer pain is also mainly indirect, as many inflammatory mediators and signaling pathways overlap with SASP biology without demonstrating that they originate from senescent cells. This review discusses these differences in evidence and examines the possible value of senolytic and senomorphic strategies in chronic pain. Further studies are needed to identify relevant senescent cell populations, establish reliable biomarkers, and clarify treatment timing, safety, and off-target effects before these approaches can be translated into clinical practice.
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BibTeX
@article{wu2026cellular,
title = {{Cellular senescence in chronic pain: Mechanisms and senotherapeutic perspectives}},
author = {Ying Wu and Li-Hua Hang},
journal = {Molecular Pain},
year = {2026},
month = nov,
doi = {10.1177/17448069261505849},
url = {https://doi.org/10.1177/17448069261505849},
note = {CC BY},
}
RIS
TY - JOUR
TI - Cellular senescence in chronic pain: Mechanisms and senotherapeutic perspectives
AU - Ying Wu
AU - Li-Hua Hang
PY - 2026
DA - 2026/11/04
JO - Molecular Pain
DO - 10.1177/17448069261505849
UR - https://doi.org/10.1177/17448069261505849
AB - Chronic pain often persists after the initial injury, inflammation, or tissue stress has subsided, suggesting that sustained cellular and microenvironmental changes contribute to pain chronification. Cellular senescence may be one of the mechanisms linking persistent tissue stress with neuroinflammation and altered pain processing. Senescence or senescence-like changes have been reported in nociceptors, dorsal root ganglion neurons, glial cells, immune cells, and local tissue-resident cells in several chronic pain conditions. These changes may influence pain through senescence-associated secretory phenotype (SASP)-related signaling, which can sustain inflammation, increase nociceptor excitability, promote glial activation, and contribute to peripheral and central sensitization. The available evidence, however, is not equally strong across pain conditions. Neuropathic pain and some degenerative nociceptive pain models provide relatively direct evidence, including senescence-related phenotypes and improvement after senolytic treatment. In nociplastic pain, glial and neuroimmune changes overlap with mechanisms associated with senescence, but direct evidence of cellular senescence remains limited. Evidence in bone cancer pain is also mainly indirect, as many inflammatory mediators and signaling pathways overlap with SASP biology without demonstrating that they originate from senescent cells. This review discusses these differences in evidence and examines the possible value of senolytic and senomorphic strategies in chronic pain. Further studies are needed to identify relevant senescent cell populations, establish reliable biomarkers, and clarify treatment timing, safety, and off-target effects before these approaches can be translated into clinical practice.
SN - 1744-8069
ER -