Effects of a kappa opioid receptor antagonist on delayed postoperative pain recovery in a novel mouse sleep disorder model
IntroductionSleep disturbances have been shown to exacerbate pain sensitivity and prolong recovery from pain. However, conventional animal models of sleep disturbance, which involve physical disruptions, such as water or forced movement, might not fully represent modern human sleep disorders.Methods...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-07-01
|
| Series: | Frontiers in Pain Research |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fpain.2025.1516935/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849706637395230720 |
|---|---|
| author | Hisakatsu Ito Hisakatsu Ito Masaaki Kawakami Masashi Yoshida Sadamu Sugimoto Tomonori Takazawa |
| author_facet | Hisakatsu Ito Hisakatsu Ito Masaaki Kawakami Masashi Yoshida Sadamu Sugimoto Tomonori Takazawa |
| author_sort | Hisakatsu Ito |
| collection | DOAJ |
| description | IntroductionSleep disturbances have been shown to exacerbate pain sensitivity and prolong recovery from pain. However, conventional animal models of sleep disturbance, which involve physical disruptions, such as water or forced movement, might not fully represent modern human sleep disorders.MethodsWe utilized a novel sleep disorder model, the perpetual avoidance of water on a wheel (PAWW) model, which induces spontaneous activity, chronic stress, and abnormal sleep–wake cycles in mice. We investigated the effects of a kappa opioid receptor (KOR) antagonist, nor-binaltorphimine (nor-BNI), on pain recovery in a postoperative pain model in mice in a state of disordered sleep. After 1 week of acclimation, the mice were housed in PAWW or regular cages for 2 weeks. Sleep conditions were evaluated using electroencephalogram and electromyogram recordings, and postoperative pain recovery following plantar incision was assessed using von Frey tests. We also examined the effects of nor-BNI on pain recovery.ResultsThe evaluation showed that PAWW housing significantly increased activity during the light phase, disrupted sleep patterns, and delayed postoperative pain recovery. The administration of nor-BNI alleviated the delayed pain recovery.DiscussionThese findings suggest that sleep disorders, such as those modeled by PAWW, could delay postoperative pain recovery, and that KOR antagonists might provide therapeutic benefits in the management of delayed recovery of postoperative pain induced by sleep disorders. |
| format | Article |
| id | doaj-art-f949fee754b14e8e9e48254bf92dd3a6 |
| institution | DOAJ |
| issn | 2673-561X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pain Research |
| spelling | doaj-art-f949fee754b14e8e9e48254bf92dd3a62025-08-20T03:16:08ZengFrontiers Media S.A.Frontiers in Pain Research2673-561X2025-07-01610.3389/fpain.2025.15169351516935Effects of a kappa opioid receptor antagonist on delayed postoperative pain recovery in a novel mouse sleep disorder modelHisakatsu Ito0Hisakatsu Ito1Masaaki Kawakami2Masashi Yoshida3Sadamu Sugimoto4Tomonori Takazawa5Department of Anesthesiology, Toyama University Hospital, Toyama, Toyama, JapanDepartment of Anesthesiology and Intensive Care Unit, Gunma University Hospital, Maebashi, Gunma, JapanDepartment of Anesthesiology, Toyama University Hospital, Toyama, Toyama, JapanDepartment of Anesthesiology, Toyama University Hospital, Toyama, Toyama, JapanDepartment of Anesthesiology, Toyama University Hospital, Toyama, Toyama, JapanDepartment of Anesthesiology, Toyama University Hospital, Toyama, Toyama, JapanIntroductionSleep disturbances have been shown to exacerbate pain sensitivity and prolong recovery from pain. However, conventional animal models of sleep disturbance, which involve physical disruptions, such as water or forced movement, might not fully represent modern human sleep disorders.MethodsWe utilized a novel sleep disorder model, the perpetual avoidance of water on a wheel (PAWW) model, which induces spontaneous activity, chronic stress, and abnormal sleep–wake cycles in mice. We investigated the effects of a kappa opioid receptor (KOR) antagonist, nor-binaltorphimine (nor-BNI), on pain recovery in a postoperative pain model in mice in a state of disordered sleep. After 1 week of acclimation, the mice were housed in PAWW or regular cages for 2 weeks. Sleep conditions were evaluated using electroencephalogram and electromyogram recordings, and postoperative pain recovery following plantar incision was assessed using von Frey tests. We also examined the effects of nor-BNI on pain recovery.ResultsThe evaluation showed that PAWW housing significantly increased activity during the light phase, disrupted sleep patterns, and delayed postoperative pain recovery. The administration of nor-BNI alleviated the delayed pain recovery.DiscussionThese findings suggest that sleep disorders, such as those modeled by PAWW, could delay postoperative pain recovery, and that KOR antagonists might provide therapeutic benefits in the management of delayed recovery of postoperative pain induced by sleep disorders.https://www.frontiersin.org/articles/10.3389/fpain.2025.1516935/fullpostoperative painpain recoverysleep disorderkappa opioid receptornorbinaltorphiminedynorphin |
| spellingShingle | Hisakatsu Ito Hisakatsu Ito Masaaki Kawakami Masashi Yoshida Sadamu Sugimoto Tomonori Takazawa Effects of a kappa opioid receptor antagonist on delayed postoperative pain recovery in a novel mouse sleep disorder model Frontiers in Pain Research postoperative pain pain recovery sleep disorder kappa opioid receptor norbinaltorphimine dynorphin |
| title | Effects of a kappa opioid receptor antagonist on delayed postoperative pain recovery in a novel mouse sleep disorder model |
| title_full | Effects of a kappa opioid receptor antagonist on delayed postoperative pain recovery in a novel mouse sleep disorder model |
| title_fullStr | Effects of a kappa opioid receptor antagonist on delayed postoperative pain recovery in a novel mouse sleep disorder model |
| title_full_unstemmed | Effects of a kappa opioid receptor antagonist on delayed postoperative pain recovery in a novel mouse sleep disorder model |
| title_short | Effects of a kappa opioid receptor antagonist on delayed postoperative pain recovery in a novel mouse sleep disorder model |
| title_sort | effects of a kappa opioid receptor antagonist on delayed postoperative pain recovery in a novel mouse sleep disorder model |
| topic | postoperative pain pain recovery sleep disorder kappa opioid receptor norbinaltorphimine dynorphin |
| url | https://www.frontiersin.org/articles/10.3389/fpain.2025.1516935/full |
| work_keys_str_mv | AT hisakatsuito effectsofakappaopioidreceptorantagonistondelayedpostoperativepainrecoveryinanovelmousesleepdisordermodel AT hisakatsuito effectsofakappaopioidreceptorantagonistondelayedpostoperativepainrecoveryinanovelmousesleepdisordermodel AT masaakikawakami effectsofakappaopioidreceptorantagonistondelayedpostoperativepainrecoveryinanovelmousesleepdisordermodel AT masashiyoshida effectsofakappaopioidreceptorantagonistondelayedpostoperativepainrecoveryinanovelmousesleepdisordermodel AT sadamusugimoto effectsofakappaopioidreceptorantagonistondelayedpostoperativepainrecoveryinanovelmousesleepdisordermodel AT tomonoritakazawa effectsofakappaopioidreceptorantagonistondelayedpostoperativepainrecoveryinanovelmousesleepdisordermodel |