Genetic Variation A118G in the OPRM1 Gene Underlies the Dimorphic Response to Epidural Opioid-Induced Itch

doi:10.1007/s12264-025-01411-6

. 2025 May 17.

doi: 10.1007/s12264-025-01411-6. Online ahead of print.

Genetic Variation A118G in the OPRM1 Gene Underlies the Dimorphic Response to Epidural Opioid-Induced Itch

Xiaomeng Zhou^#¹, Ai-Lun Li^#¹, Wan-Jie Du^#¹, Pengyu Gao¹, Bin Lai², Fang Fang³, Qingjian Han⁴, Jing Cang⁵

Affiliations

¹ Department of Anesthesia, Department of Pain Medicine, Zhongshan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontier Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, 200032, China.
² Department of Anesthesia, Department of Pain Medicine, Zhongshan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontier Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, 200032, China. laibin@fudan.edu.cn.
³ Department of Anesthesia, Department of Pain Medicine, Zhongshan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontier Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, 200032, China. fang.fang@zs-hospital.sh.cn.
⁴ Department of Anesthesia, Department of Pain Medicine, Zhongshan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontier Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, 200032, China. qingjianhan@fudan.edu.cn.
⁵ Department of Anesthesia, Department of Pain Medicine, Zhongshan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontier Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, 200032, China. cang.jing@zs-hospital.sh.cn.

^# Contributed equally.

PMID: 40381142
DOI: 10.1007/s12264-025-01411-6

Genetic Variation A118G in the OPRM1 Gene Underlies the Dimorphic Response to Epidural Opioid-Induced Itch

Xiaomeng Zhou et al. Neurosci Bull. 2025.

. 2025 May 17.

doi: 10.1007/s12264-025-01411-6. Online ahead of print.

Authors

Xiaomeng Zhou^#¹, Ai-Lun Li^#¹, Wan-Jie Du^#¹, Pengyu Gao¹, Bin Lai², Fang Fang³, Qingjian Han⁴, Jing Cang⁵

Affiliations

¹ Department of Anesthesia, Department of Pain Medicine, Zhongshan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontier Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, 200032, China.
² Department of Anesthesia, Department of Pain Medicine, Zhongshan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontier Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, 200032, China. laibin@fudan.edu.cn.
³ Department of Anesthesia, Department of Pain Medicine, Zhongshan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontier Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, 200032, China. fang.fang@zs-hospital.sh.cn.
⁴ Department of Anesthesia, Department of Pain Medicine, Zhongshan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontier Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, 200032, China. qingjianhan@fudan.edu.cn.
⁵ Department of Anesthesia, Department of Pain Medicine, Zhongshan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontier Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, 200032, China. cang.jing@zs-hospital.sh.cn.

^# Contributed equally.

PMID: 40381142
DOI: 10.1007/s12264-025-01411-6

Abstract

Neuraxial opioids, widely used in obstetric and perioperative pain management, often lead to unwanted itch, reducing patient satisfaction. While the μ-opioid receptor has been implicated in opioid-induced itch, the genetic basis for variable itch incidence remains unknown. This study examined 3616 patients receiving epidural opioids, revealing an itch occurrence of 26.55%, with variations among opioid types and gender. Analysis of the OPRM1 gene identified six single-nucleotide polymorphisms, notably rs1799971 (A118G), that correlated with opioid-induced itch. Mouse models with an equivalent A112G mutation showed reduced neuraxial opioid-induced itch and light touch-evoked itch, mirroring human findings. The 118G allele demonstrated an anti-itch effect without impacting analgesia, addiction, or tolerance, offering insights for risk stratification and potential anti-itch pretreatment strategies.

Keywords: Itch; MOR; Opioids; SNPs.

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Conflict of interest statement

Conflict of interest: The authors have no financial interest conflicts in this paper.

References

1. Ko MC. Neuraxial opioid-induced itch and its pharmacological antagonism. Handb Exp Pharmacol 2015, 226: 315–335. - DOI - PubMed - PMC
1. Nguyen E, Lim G, Ross SE. Evaluation of therapies for peripheral and neuraxial opioid-induced pruritus based on molecular and cellular discoveries. Anesthesiology 2021, 135: 350–365. - DOI - PubMed
1. Ko MCH, Song MS, Edwards T, Lee H, Naughton NN. The role of central mu opioid receptors in opioid-induced itch in Primates. J Pharmacol Exp Ther 2004, 310: 169–176. - DOI - PubMed
1. Liu XY, Liu ZC, Sun YG, Ross M, Kim S, Tsai FF. Unidirectional cross-activation of GRPR by MOR1D uncouples itch and analgesia induced by opioids. Cell 2011, 147: 447–458. - DOI - PubMed - PMC
1. Nguyen E, Lim G, Ding H, Hachisuka J, Ko MC, Ross SE. Morphine acts on spinal dynorphin neurons to cause itch through disinhibition. Sci Transl Med 2021, 13: eabc3774. - DOI - PubMed

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[1] Ko MC. Neuraxial opioid-induced itch and its pharmacological antagonism. Handb Exp Pharmacol 2015, 226: 315–335. - DOI - PubMed - PMC

[2] Ko MC. Neuraxial opioid-induced itch and its pharmacological antagonism. Handb Exp Pharmacol 2015, 226: 315–335. - DOI - PubMed - PMC

[3] Nguyen E, Lim G, Ross SE. Evaluation of therapies for peripheral and neuraxial opioid-induced pruritus based on molecular and cellular discoveries. Anesthesiology 2021, 135: 350–365. - DOI - PubMed

[4] Nguyen E, Lim G, Ross SE. Evaluation of therapies for peripheral and neuraxial opioid-induced pruritus based on molecular and cellular discoveries. Anesthesiology 2021, 135: 350–365. - DOI - PubMed

[5] Ko MCH, Song MS, Edwards T, Lee H, Naughton NN. The role of central mu opioid receptors in opioid-induced itch in Primates. J Pharmacol Exp Ther 2004, 310: 169–176. - DOI - PubMed

[6] Ko MCH, Song MS, Edwards T, Lee H, Naughton NN. The role of central mu opioid receptors in opioid-induced itch in Primates. J Pharmacol Exp Ther 2004, 310: 169–176. - DOI - PubMed

[7] Liu XY, Liu ZC, Sun YG, Ross M, Kim S, Tsai FF. Unidirectional cross-activation of GRPR by MOR1D uncouples itch and analgesia induced by opioids. Cell 2011, 147: 447–458. - DOI - PubMed - PMC

[8] Liu XY, Liu ZC, Sun YG, Ross M, Kim S, Tsai FF. Unidirectional cross-activation of GRPR by MOR1D uncouples itch and analgesia induced by opioids. Cell 2011, 147: 447–458. - DOI - PubMed - PMC

[9] Nguyen E, Lim G, Ding H, Hachisuka J, Ko MC, Ross SE. Morphine acts on spinal dynorphin neurons to cause itch through disinhibition. Sci Transl Med 2021, 13: eabc3774. - DOI - PubMed

[10] Nguyen E, Lim G, Ding H, Hachisuka J, Ko MC, Ross SE. Morphine acts on spinal dynorphin neurons to cause itch through disinhibition. Sci Transl Med 2021, 13: eabc3774. - DOI - PubMed

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Genetic Variation A118G in the OPRM1 Gene Underlies the Dimorphic Response to Epidural Opioid-Induced Itch

Affiliations

Genetic Variation A118G in the OPRM1 Gene Underlies the Dimorphic Response to Epidural Opioid-Induced Itch

Authors

Affiliations

Abstract

Conflict of interest statement

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