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Mol Brain ; 14(1): 146, 2021 09 20.
Article in English | MEDLINE | ID: mdl-34544461

ABSTRACT

Chronic postsurgical pain (CPSP) is a serious problem. We developed a mouse model of CPSP induced by electrocautery and examined the mechanism of CPSP. In this mouse model, while both incision and electrocautery each produced acute allodynia, persistent allodynia was only observed after electrocautery. Under these conditions, we found that the mRNA levels of Small proline rich protein 1A (Sprr1a) and Annexin A10 (Anxa10), which are the key modulators of neuropathic pain, in the spinal cord were more potently and persistently increased by electrocautery than by incision. Furthermore, these genes were overexpressed almost exclusively in chronic postsurgical pain-activated neurons. This event was associated with decreased levels of tri-methylated histone H3 at Lys27 and increased levels of acetylated histone H3 at Lys27 at their promoter regions. On the other hand, persistent allodynia and overexpression of Sprr1a and Anxa10 after electrocautery were dramatically suppressed by systemic administration of GSK-J4, which is a selective H3K27 demethylase inhibitor. These results suggest that the effects of electrocautery contribute to CPSP along with synaptic plasticity and epigenetic modification.


Subject(s)
Annexins/biosynthesis , Cornified Envelope Proline-Rich Proteins/biosynthesis , Electrocoagulation/adverse effects , Histone Code , Hyperalgesia/etiology , Nerve Tissue Proteins/biosynthesis , Neuralgia/genetics , Neurons/physiology , Pain, Postoperative/genetics , Spinal Cord/physiopathology , Animals , Annexins/genetics , Benzazepines/pharmacology , Benzazepines/therapeutic use , Cornified Envelope Proline-Rich Proteins/genetics , Disease Models, Animal , Female , Foot Injuries/physiopathology , Gene Expression Regulation , Gene Knock-In Techniques , Genes, Reporter , Genes, fos , Histones/metabolism , Hyperalgesia/drug therapy , Hyperalgesia/physiopathology , Jumonji Domain-Containing Histone Demethylases/antagonists & inhibitors , Lysine/metabolism , Male , Methylation , Mice , Mice, Inbred C57BL , Nerve Tissue Proteins/genetics , Neuralgia/drug therapy , Neuralgia/physiopathology , Neurons/drug effects , Pain, Postoperative/drug therapy , Pain, Postoperative/physiopathology , Pyrimidines/pharmacology , Pyrimidines/therapeutic use , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Tamoxifen/analogs & derivatives , Tamoxifen/pharmacology
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