Dataset Information

Histone modification of pain-related gene expression in spinal cord neurons under a persistent postsurgical pain-like state by electrocautery.

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.

SUBMITTER: Katsuda Y

PROVIDER: S-EPMC8451106 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Histone modification of pain-related gene expression in spinal cord neurons under a persistent postsurgical pain-like state by electrocautery.

Katsuda Yosuke Y Tanaka Kenichi K Mori Tomohisa T Narita Michiko M Takeshima Hideyuki H Kondo Takashige T Yamabe Yoshiyuki Y Matsufuji Misa M Sato Daisuke D Hamada Yusuke Y Yamaguchi Keisuke K Ushijima Toshikazu T Inada Eiichi E Kuzumaki Naoko N Iseki Masako M Narita Minoru M

Molecular brain 20210920 1

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]

PMID: 34544461

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Project description:BackgroundSpinal Cord Stimulation (SCS) may provide pain relief in patients with therapy-refractory Persistent Spinal Pain Syndrome Type II (PSPS-T2). Despite the evidence that SCS can reduce disability and reduce pain medication usage, only 25% of the patients is able to completely omit pain medication usage after 12 months of SCS. To tackle the high burden of patients who consume a lot of pain medication, tapering programs could be initiated before starting a trajectory with SCS. The current objective is to examine whether a pain medication tapering program before SCS alters disability in PSPS-T2 patients compared to no tapering program.Methods and designA three-arm, parallel-group multicenter randomized controlled trial will be conducted including 195 patients who will be randomized (1:1:1) to either (a) a standardized pain medication tapering program, (b) a personalized pain medication tapering program, or (c) no tapering program before SCS implantation, all with a follow-up period until 12 months after implantation. The primary outcome is disability. The secondary outcomes are pain intensity, health-related quality of life, participation, domains affected by substance use, anxiety and depression, medication usage, psychological constructs, sleep, symptoms of central sensitization, and healthcare expenditure.DiscussionWithin the PIANISSIMO project we propose a way to reduce the risks of adverse events, medication-induced hyperalgesia, tolerance, and dependence by providing pain medication tapering before SCS. Due to the lack of a commonly accepted in-hospital tapering approach, two different tapering programs will be evaluated in this study. If pain medication tapering programs are deemed to be more effective than no tapering on disability, this would add to the evidence towards an improved patient-centered care model in this patient group and set a clear path to advocate for pain medication tapering before SCS as the new standard treatment guideline for these patients.Trial registrationClinicalTrials.gov NCT05861609. Registered on May 17, 2023.

Dataset Information

Histone modification of pain-related gene expression in spinal cord neurons under a persistent postsurgical pain-like state by electrocautery.

Publications

Histone modification of pain-related gene expression in spinal cord neurons under a persistent postsurgical pain-like state by electrocautery.

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