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HDAC6-selective inhibitors decrease nerve-injury and inflammation-associated mechanical hypersensitivity in mice
- Source :
- Psychopharmacology (Berl)
- Publication Year :
- 2020
-
Abstract
- BACKGROUND: HDAC6 is a class IIB histone deacetylase expressed at many levels of the nociceptive pathway. This study tested the ability of novel and selective HDAC6 inhibitors to alleviate sensory hypersensitivity behaviors in mouse models of peripheral nerve injury and peripheral inflammation. METHODS: We utilized the murine spared nerve injury (SNI) model for peripheral nerve injury and the Complete Freund’s Adjuvant (CFA) model of peripheral inflammation. We applied the Von Frey assay to monitor mechanical allodynia. RESULTS: Using the SNI model, we demonstrate that daily administration of the brain-penetrant HDAC6 inhibitor, ACY-738, abolishes mechanical allodynia in male and in female mice. Importantly, there is no tolerance to the antiallodynic actions of these compounds as they produce a consistent increase in Von Frey thresholds for several weeks. We observed a similar antiallodynic effect when utilizing the HDAC6 inhibitor, ACY-257, which shows limited brain expression when administered systemically. We also demonstrate that ACY-738 and ACY-257 attenuate mechanical allodynia in the CFA model of peripheral inflammation. CONCLUSIONS: Overall, our findings suggest that inhibition of HDAC6 provides a promising therapeutic avenue for the alleviation of mechanical allodynia associated with peripheral nerve injury and peripheral inflammation.
- Subjects :
- Male
SNi
Inflammation
Pharmacology
Histone Deacetylase 6
Hydroxamic Acids
Article
Rats, Sprague-Dawley
03 medical and health sciences
Mice
0302 clinical medicine
medicine
Animals
Pain Measurement
business.industry
HDAC6
Nerve injury
030227 psychiatry
Peripheral
Rats
Histone Deacetylase Inhibitors
Mice, Inbred C57BL
Nociception
Pyrimidines
Hyperalgesia
Neuropathic pain
Peripheral nerve injury
medicine.symptom
business
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Psychopharmacology (Berl)
- Accession number :
- edsair.doi.dedup.....82412ee760cd897ea2f18b6be51fcd45