SCN11A variants may influence postoperative pain sensitivity after gynecological surgery in Chinese Han female patients

Sun, Jiaoli; Duan, Guangyou; Guo, Shanna; Zhang, Yuhao; Ying, Ying; Zhang, Mi; Wang, Qingli; Liu, Jingyu; Zhang, Xianwei

doi:10.1097/md.0000000000008149

Cited by 16 publications

(16 citation statements)

References 42 publications

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“…It is now known that there are nine voltage-gated sodium channel subtypes along with numerous splice variants. Of note, three of these isotypes: Na V 1.7 16,17 , Na V 1.8 [18][19][20] , and Na V 1.9 21,22 have been found to be principally expressed in primary afferent nociceptors. The relevance of these isotypes to human pain has been suggested by the observation that a loss-of-function mutation in Na V 1.7 (SCN9A) leads to congenital insensitivity to pain (CIP), a rare genetic disorder.…”

Section: Introductionmentioning

confidence: 99%

“…Further, it is not clear that such antibodies can gain access to the appropriate Na V 1.7 channels and yield a reliable block of their function. Consequently, in spite of preclinical studies demonstrating that decreased Na V 1.7 activity leads to a reduction in inflammatory and neuropathic pain [16][17][18][19][20][21][22]37 , no molecule targeting this gene product has reached the final phase of clinical trials 32 . We therefore took an alternative approach by epigenetically modulating the expression of Na V 1.7 using two genome engineering tools, clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 (CRISPR-Cas9) and zinc-finger proteins (ZFP), such that one could engineer highly specific, long-lasting and reversible treatments for pain.…”

Section: Introductionmentioning

confidence: 99%

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Long-lasting Analgesia via Targetedin vivoEpigenetic Repression of Nav1.7

Moreno

Catroli

Alemán

et al. 2019

Preprint

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One sentence summary:In situ epigenome engineering approach for genomically scarless, durable, and non-addictive management of pain. ABSTRACTCurrent treatments for chronic pain rely largely on opioids despite their unwanted side effects and risk of addiction. Genetic studies have identified in humans key targets pivotal to nociceptive processing, with the voltage-gated sodium channel, Na V 1.7 (SCN9A), being perhaps the most promising candidate for analgesic drug development.Specifically, a hereditary loss-of-function mutation in Na V 1.7 leads to insensitivity to pain without other neurodevelopmental alterations. However, the high sequence similarity between Na V subtypes has frustrated efforts to develop selective inhibitors. Here, we investigated targeted epigenetic repression of Na V 1.7 via genome engineering approaches based on clustered regularly interspaced short palindromic repeats (CRISPR)-dCas9 and zinc finger proteins as a potential treatment for chronic pain.Towards this end, we first optimized the efficiency of Na V 1.7 repression in vitro in Neuro2A cells, and then by the lumbar intrathecal route delivered both genomeengineering platforms via adeno-associated viruses (AAVs) to assess their effects in three mouse models of pain: carrageenan-induced inflammatory pain, paclitaxel-induced neuropathic pain and BzATP-induced pain. Our results demonstrate: one, effective repression of Na V 1.7 in lumbar dorsal root ganglia; two, reduced thermal hyperalgesia in the inflammatory state; three, decreased tactile allodynia in the neuropathic state; and four, no changes in normal motor function. We anticipate this genomically scarless and non-addictive pain amelioration approach enabling Long-lasting Analgesia via Targeted in vivo Epigenetic Repression of Nav1.7, a methodology we dub pain LATER, will have significant therapeutic potential, such as for preemptive administration in 2 anticipation of a pain stimulus (pre-operatively), or during an established chronic pain state.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Long-lasting Analgesia via Targetedin vivoEpigenetic Repression of Nav1.7

Moreno

Catroli

Alemán

et al. 2019

Preprint

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“…In this study, we identified two SNPs (rs33985936, rs11709492) were associated with inadequate analgesia. The mutation of rs33985936 (2725C > T) causes amino acid substitution Val909Ile which leads to the changes in intermolecular force of Nav1.9 [17]. Previous study reported that subjects who carrying the minor allele of rs33985936 were more sensitive to pain, while patients carrying the minor allele of rs11709492 have lower pain sensitivity [17].…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, except for OPRM1, ABCB1, UGT2B7, and P2RX7, we selected other 14 genes known to be involved in systems related to pain perception and modulation based on evidence in the literature. The selected genes have been related to the ion channels (SCN9A, SCN10A, SCN11A, KCNJ6, TRPV1, and CACN A1E) [15][16][17][18][19][20], dopaminergic system (COMT, DRD2) [21,22], purinergic receptor (P2RY12) [23], adrenergic receptor (ADRB1) [24], estrogen receptor (ESR1) [25], serine/ threonine kinase (TAOK3) [26], growth factors (TGFB1) [27], and transcription factor (CREB1) [28]. The aim of the present study was to evaluate the association of common SNPs among aforementioned genes with the inadequate analgesia after single-port VATS.…”

Section: Introductionmentioning

confidence: 99%

Single nucleotide polymorphisms associated with postoperative inadequate analgesia after single-port VATS in Chinese population

et al. 2020

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Background: Postoperative inadequate analgesia following video-assisted thoracoscopic surgery (VATS) is a common and significant clinical problem. While genetic polymorphisms may play role in the variability of postoperative analgesia effect, few studies have evaluated the associations between genetic mutations and inadequate analgesia after single-port VATS. Methods: Twenty-eight single nucleotide polymorphisms (SNPs) among 18 selected genes involved in pain perception and modulation were genotyped in 198 Chinese patients undergoing single-port VATS. The primary outcome was the occurrence of inadequate analgesia in the first night and morning after surgery which was defined by a comprehensive postoperative evaluation. Multivariable logistic regression analyses were used to identify the association between genetic variations and postoperative inadequate analgesia. Results: The prevalence of postoperative inadequate analgesia was 45.5% in the present study. After controlling for age and education level, association with inadequate analgesia was observed in four SNPs among three genes encoding voltage-gated sodium channels. Patients with the minor allele of rs33985936 (SCN11A), rs6795970 (SCN10A), and 3312G > T (SCN9A) have an increased risk of suffering from inadequate analgesia. While the patients carrying the minor allele of rs11709492 (SCN11A) have lower risk experiencing inadequate analgesia. Conclusions: We identified that SNPs in SCN9A, SCN10A, and SCN11A play a role in the postoperative inadequate analgesia after single-port VATS. Although future larger and long-term follow up studies are warranted to confirm our findings, the results of the current study may be utilized as predictors for forecasting postoperative analgesic effect for patients receiving this type of surgery. Trial registration: This study was retrospectively registered in the ClinicalTrials.gov Registry (NCT03916120) on April 16, 2019.

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“…In the present study, except for OPRM1, ABCB1, UGT2B7, and P2RX7, we selected other 14 genes known to be involved in systems related to pain perception and modulation based on evidence in the literature. The selected genes have been related to the ion channels (SCN9A, SCN10A, SCN11A, KCNJ6, TRPV1, and CACNA1E), [15][16][17][18][19][20] dopaminergic system (COMT, DRD2), [21,22] purinergic receptor (P2RY12),[23] adrenergic receptor (ADRB1), [24] estrogen receptor (ESR1), [25] serine/threonine kinase (TAOK3), [26] growth factors (TGFB1), [27] and transcription factor (CREB1). [28] The aim of the present study was to evaluate the association of common SNPs among aforementioned genes with the inadequate analgesia after single-port VATS.…”

mentioning

confidence: 99%

Single nucleotide polymorphisms associated with postoperative inadequate analgesia after single-port VATS in Chinese population

Xing

Bai

Sun

et al. 2020

Preprint

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Background: Postoperative inadequate analgesia following video-assisted thoracoscopic surgery (VATS) is a common and significant clinical problem. While genetic polymorphisms may play role in the variability of postoperative analgesia effect, few studies have evaluated the associations between genetic mutations and inadequate analgesia after single-port VATS. Methods: Twenty-eight single nucleotide polymorphisms (SNPs) among 18 selected genes involved in pain perception and modulation were genotyped in 198 Chinese patients undergoing single-port VATS. The primary outcome was the occurrence of inadequate analgesia in the first night and morning after surgery which was defined by a comprehensive postoperative evaluation. Multivariable logistic regression analyses were used to identify the association between genetic variations and postoperative inadequate analgesia. Results: The prevalence of postoperative inadequate analgesia was 45.5% in the present study. After controlling for age and education level, association with inadequate analgesia was observed in four SNPs among three genes encoding voltage-gated sodium channels. Patients with the minor allele of rs33985936 (SCN11A), rs6795970 (SCN10A), and 3312G>T (SCN9A) have an increased risk of suffering from inadequate analgesia. While the patients carrying the minor allele of rs11709492 (SCN11A) have lower risk experiencing inadequate analgesia. Conclusions: We identified that SNPs in SCN9A, SCN10A, and SCN11A play a role in the postoperative inadequate analgesia after single-port VATS. Although future larger and long-term follow up studies are warranted to confirm our findings, the results of the current study may be utilized as predictors for forecasting postoperative analgesic effect for patients receiving this type of surgery.Trial registration: This study was retrospectively registered in the ClinicalTrials.gov Registry (NCT03916120) on April 16, 2019.

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SCN11A variants may influence postoperative pain sensitivity after gynecological surgery in Chinese Han female patients

Abstract: Supplemental Digital Content is available in the text

Cited by 16 publications

References 42 publications

Long-lasting Analgesia via Targetedin vivoEpigenetic Repression of Nav1.7

Long-lasting Analgesia via Targetedin vivoEpigenetic Repression of Nav1.7

Single nucleotide polymorphisms associated with postoperative inadequate analgesia after single-port VATS in Chinese population

Single nucleotide polymorphisms associated with postoperative inadequate analgesia after single-port VATS in Chinese population

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