Heterogeneity in patterns of pain development after nerve injury in rats and the influence of sex
The genesis of neuropathic pain is complex, as sensory abnormalities may differ between patients with different or similar etiologies, suggesting mechanistic heterogeneity, a concept that is largely unexplored. Yet, data are usually grouped for analysis based on the assumption that they share the sa...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2021-08-01
|
| Series: | Neurobiology of Pain |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452073X21000106 |
| _version_ | 1818383796580384768 |
|---|---|
| author | Katherine Sherman Victoria Woyach James C. Eisenach Francis A. Hopp Freddy Cao Quinn H. Hogan Caron Dean |
| author_facet | Katherine Sherman Victoria Woyach James C. Eisenach Francis A. Hopp Freddy Cao Quinn H. Hogan Caron Dean |
| author_sort | Katherine Sherman |
| collection | DOAJ |
| description | The genesis of neuropathic pain is complex, as sensory abnormalities may differ between patients with different or similar etiologies, suggesting mechanistic heterogeneity, a concept that is largely unexplored. Yet, data are usually grouped for analysis based on the assumption that they share the same underlying pathogenesis. Sex is a factor that may contribute to differences in pain responses. Neuropathic pain is more prevalent in female patients, but pre-clinical studies that can examine pain development in a controlled environment have typically failed to include female subjects. This study explored patterns of development of hyperalgesia-like behavior (HLB) induced by noxious mechanical stimulation in a neuropathic pain model (spared nerve injury, SNI) in both male and female rats, and autonomic dysfunction that is associated with chronic pain. HLB was analyzed across time, using both discrete mixture modeling and rules-based longitudinal clustering. Both methods identified similar groupings of hyperalgesia trajectories after SNI that were not evident when data were combined into groups by sex only. Within the same hyperalgesia development group, mixed models showed that development of HLB in females was delayed relative to males and reached a magnitude similar to or higher than males. The data also indicate that sympathetic tone (as indicated by heart rate variability) drops below pre-SNI level before or at the onset of development of HLB. This study classifies heterogeneity in individual development of HLB and identifies sexual dimorphism in the time course of development of neuropathic pain after nerve injury. Future studies addressing mechanisms underlying these differences could facilitate appropriate pain treatments. |
| first_indexed | 2024-12-14T03:12:04Z |
| format | Article |
| id | doaj.art-82906cf37ae14ebc92a32a7815a13e4e |
| institution | Directory Open Access Journal |
| issn | 2452-073X |
| language | English |
| last_indexed | 2024-12-14T03:12:04Z |
| publishDate | 2021-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Pain |
| spelling | doaj.art-82906cf37ae14ebc92a32a7815a13e4e2022-12-21T23:19:15ZengElsevierNeurobiology of Pain2452-073X2021-08-0110100069Heterogeneity in patterns of pain development after nerve injury in rats and the influence of sexKatherine Sherman0Victoria Woyach1James C. Eisenach2Francis A. Hopp3Freddy Cao4Quinn H. Hogan5Caron Dean6Research Division, Zablocki Veterans Affairs Medical Center, Milwaukee, WI 53295, United StatesResearch Division, Zablocki Veterans Affairs Medical Center, Milwaukee, WI 53295, United States; Department of Anesthesiology, Medical College of Wisconsin and Zablocki Veterans Affairs Medical Center, Milwaukee, WI 53226, United StatesDepartment of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC 27157, United StatesResearch Division, Zablocki Veterans Affairs Medical Center, Milwaukee, WI 53295, United StatesCollege of Nursing, University of Wisconsin – Milwaukee3, Milwaukee, WI 53222, United StatesResearch Division, Zablocki Veterans Affairs Medical Center, Milwaukee, WI 53295, United States; Department of Anesthesiology, Medical College of Wisconsin and Zablocki Veterans Affairs Medical Center, Milwaukee, WI 53226, United StatesResearch Division, Zablocki Veterans Affairs Medical Center, Milwaukee, WI 53295, United States; Department of Anesthesiology, Medical College of Wisconsin and Zablocki Veterans Affairs Medical Center, Milwaukee, WI 53226, United States; Corresponding author at: Department of Anesthesiology, Research Service 151, Zablocki VA Medical Center, Milwaukee, WI 53295, United States.The genesis of neuropathic pain is complex, as sensory abnormalities may differ between patients with different or similar etiologies, suggesting mechanistic heterogeneity, a concept that is largely unexplored. Yet, data are usually grouped for analysis based on the assumption that they share the same underlying pathogenesis. Sex is a factor that may contribute to differences in pain responses. Neuropathic pain is more prevalent in female patients, but pre-clinical studies that can examine pain development in a controlled environment have typically failed to include female subjects. This study explored patterns of development of hyperalgesia-like behavior (HLB) induced by noxious mechanical stimulation in a neuropathic pain model (spared nerve injury, SNI) in both male and female rats, and autonomic dysfunction that is associated with chronic pain. HLB was analyzed across time, using both discrete mixture modeling and rules-based longitudinal clustering. Both methods identified similar groupings of hyperalgesia trajectories after SNI that were not evident when data were combined into groups by sex only. Within the same hyperalgesia development group, mixed models showed that development of HLB in females was delayed relative to males and reached a magnitude similar to or higher than males. The data also indicate that sympathetic tone (as indicated by heart rate variability) drops below pre-SNI level before or at the onset of development of HLB. This study classifies heterogeneity in individual development of HLB and identifies sexual dimorphism in the time course of development of neuropathic pain after nerve injury. Future studies addressing mechanisms underlying these differences could facilitate appropriate pain treatments.http://www.sciencedirect.com/science/article/pii/S2452073X21000106Neuropathic painHyperalgesiaSex differenceAutonomicCluster analysis |
| spellingShingle | Katherine Sherman Victoria Woyach James C. Eisenach Francis A. Hopp Freddy Cao Quinn H. Hogan Caron Dean Heterogeneity in patterns of pain development after nerve injury in rats and the influence of sex Neurobiology of Pain Neuropathic pain Hyperalgesia Sex difference Autonomic Cluster analysis |
| title | Heterogeneity in patterns of pain development after nerve injury in rats and the influence of sex |
| title_full | Heterogeneity in patterns of pain development after nerve injury in rats and the influence of sex |
| title_fullStr | Heterogeneity in patterns of pain development after nerve injury in rats and the influence of sex |
| title_full_unstemmed | Heterogeneity in patterns of pain development after nerve injury in rats and the influence of sex |
| title_short | Heterogeneity in patterns of pain development after nerve injury in rats and the influence of sex |
| title_sort | heterogeneity in patterns of pain development after nerve injury in rats and the influence of sex |
| topic | Neuropathic pain Hyperalgesia Sex difference Autonomic Cluster analysis |
| url | http://www.sciencedirect.com/science/article/pii/S2452073X21000106 |
| work_keys_str_mv | AT katherinesherman heterogeneityinpatternsofpaindevelopmentafternerveinjuryinratsandtheinfluenceofsex AT victoriawoyach heterogeneityinpatternsofpaindevelopmentafternerveinjuryinratsandtheinfluenceofsex AT jamesceisenach heterogeneityinpatternsofpaindevelopmentafternerveinjuryinratsandtheinfluenceofsex AT francisahopp heterogeneityinpatternsofpaindevelopmentafternerveinjuryinratsandtheinfluenceofsex AT freddycao heterogeneityinpatternsofpaindevelopmentafternerveinjuryinratsandtheinfluenceofsex AT quinnhhogan heterogeneityinpatternsofpaindevelopmentafternerveinjuryinratsandtheinfluenceofsex AT carondean heterogeneityinpatternsofpaindevelopmentafternerveinjuryinratsandtheinfluenceofsex |