Gender Differences in Pain Experience and Treatment after Motor Vehicle Collisions: A Secondary Analysis of the CRASH Injury Study

Madsen, Tracy E.; McLean, Samuel A.; Zhai, Wanting; Linnstaedt, Sarah D.; Kurz, Michael C.; Swor, Robert A.; Hendry, Phyllis L.; Peak, David A.; Lewandowski, Christopher; Pearson, Claire; O’Neil, Brian J.; Datner, Elizabeth M.; Lee, David; Beaudoin, Francesca L.

doi:10.1016/j.clinthera.2017.12.014

Cited by 18 publications

(7 citation statements)

References 38 publications

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“…Most individuals who develop CMSP/PTSS following MVC are women. [16][17][18] This fact is consistent with the marked increase in CMSP and PTSS burden experienced by women vs. men in other settings. [19][20][21][22][23][24][25] Additionally, data from animal models suggest that there are sex differences in response to stress/priming events that lead to increased hyperalgesia and deficits in fear extinction [26][27][28][29][30] .…”

Section: Introductionsupporting

confidence: 76%

Genes known to escape X chromosome inactivation predict co‐morbid chronic musculoskeletal pain and posttraumatic stress symptom development in women following trauma exposure

Chen

Pan

et al. 2018

American J of Med Genetics Pt B

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Co-morbid chronic musculoskeletal pain (CMSP) and posttraumatic stress symptoms (PTSS) are frequent sequelae of motor vehicle collision (MVC), are associated with greater disability than either outcome alone, and are more prevalent in women vs men. In the current study we assessed for evidence that gene transcripts originating from the X chromosome (XCh) contribute to sex differences in vulnerability to CMSP/PTSS after MVC. Nested samples were drawn from a longitudinal study of African American individuals, and CMSP (0-10 Numeric Rating Scale) and PTSS (Impact of Events Scale, Revised) outcomes were assessed six months following MVC. Blood RNA were sequenced (n=101) and the relationship between XCh mRNA expression levels and co-morbid CMSP/PTSS outcomes was evaluated using logistic regression analyses. A disproportionate number of peritraumatic XCh mRNA predicting CMSP/PTSS in women were genes previously found to escape XCh inactivation (XCI) (11/40, z=-2.9, p=0.004). Secondary analyses assessing gene ontology relationships between these genes identified an enrichment in genes known to influence neuronal plasticity. Further, the relationship of expression of two critical regulators of XCI, XIST and YY1, was different in women developing CMSP/PTSS. Together, these data suggest that XCh genes that escape inactivation may contribute to sex differences in vulnerability to CMSP/PTSS after MVC.

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Section: Introductionsupporting

confidence: 76%

Genes known to escape X chromosome inactivation predict co‐morbid chronic musculoskeletal pain and posttraumatic stress symptom development in women following trauma exposure

Chen

Pan

et al. 2018

American J of Med Genetics Pt B

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“…Interestingly, female sex is associated with pain over the first 12 months. This sex difference showing increased reporting of pain by females after trauma is seen previously in research including a study (>1800 patients) after motor vehicle accidents in which women produced higher scores on the pain catastrophizing scale 23 . However, sex was not related to functional outcome despite this relationship with pain in our cohort.…”

Section: Discussionsupporting

confidence: 83%

Epidemiology and 12-Month Outcomes of Patients Managed in a Thoracolumbosacral Orthosis After Trauma

Webb,

Kimmel,

D’Souza

et al. 2023

J Prosthet Orthot

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Introduction Traumatic fractures of the thoracolumbar junction (T10–L3) are the most common fractures of the spinal column. The management of these injuries can be operative or nonoperative, and braces are often used, including the Boston Overlap Brace (BOB), a type of thoracolumbosacral orthosis (TSLO). Methods All patients admitted to the Alfred Hospital in 2015 and managed in a BOB for 2- or 3-column thoracolumbar burst fractures (without neurology) were included in the study. In-hospital and 6- and 12-month patient-reported outcome measures were collected. A random-effects regression model analysis for each outcome (self-reported) pain and functional outcome measures by the Glasgow Outcomes Scale–Extended (GOS-E) was undertaken. Results A total of 115 patients (62 male) were included with a median age of 53 years. Using a random-effects model, having a lower-limb fracture or a regional kyphosis angle >8° was associated with not having a good recovery after taking into account all other factors with a univariate relationship with this outcome. In terms of the outcome of self-reported pain, only female sex was associated with reporting pain. Conclusions This study included a large cohort of patients with management of a traumatic fracture with a BOB-type TLSO and provided information that should guide a larger study to review whether the factors associated with poorer outcome, including female sex and local kyphotic angle, need to be considered before deciding on the management of these fractures. Clinical Relevance The association between degree of deformity of fracture (>8°) and associated lower-limb injury with poorer patient outcomes may need to be taken into account before deciding to manage thoracolumbar fractures with a BOB-type TLSO although further longitudinal studies are required.

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“…This observation may enhance severity of symptoms and longer-term pain catastrophizing in women following traumatic injury and musculoskeletal disorders [41][42][43][44][45][46] . The preponderance of our imaging and behavioral observations suggests an important role of NLRP3 in ammasome-mediated caspase-1 activation following repetitive mTBI in both the initiating and modulating long-term behavioral sequelae.…”

Section: Discussionmentioning

confidence: 99%

Repeated Closed-Head Mild Traumatic Brain Injury Induces Robust Caspase-1 Mediated Inflammation that Contributes to Nociplastic Pain.

Nguyen

Cochran

et al. 2022

Preprint

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Patients who have experienced concussive mild traumatic brain injuries (mTBIs) suffer from a number of comorbidities including chronic pain. Despite extensive studies investigating the underlining mechanisms of mTBIs-associated chronic pain, the role of inflammation after brain injury, and its contribution towards long-term pain, are still poorly understood. Given the shifting dynamics of inflammation, it is important to understand the spatial-longitudinal changes and its effects on TBI-related pain. Utilizing a recently developed transgenic caspase-1 luciferase reporter mouse, we characterized the bioluminescence signal evident in both in vivo and ex vivo tissue following repetitive closed head mTBIs. This allowed us to reveal the spatiotemporal dynamics of caspase-1 activation in individual animals across time. We established that there are significant increases in bioluminescent signal upon protease cleavage in the brain, thorax, abdomen, and paws in vivo which lasted for at least one week after each injury. Enhanced inflammation also was also in ex vivo brain slice preparations following injury event that lasted for at least 3 days. Concurrent with the in vivo detection of bioluminescent signal were persistent decreases in mouse hind paw withdrawal thresholds that lasted for more than two months post-injury. Using a potent small molecule inhibitor of NLRP3 inflammasome-caspase 1 activity, MCC950, we observed reductions in both caspase-1 bioluminescent signal in vivo, caspase-1 p45 expression by immunoblot and increase in hind paw withdrawal thresholds. Overall, these findings suggest that neuroinflammation in the brain following repeated mTBIs is coincidental with a chronic nociplastic pain state, and repeated mTBI associated events can be ameliorated by a highly specific small molecule inhibitor of NLRP3 inflammasome activation.

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Gender Differences in Pain Experience and Treatment after Motor Vehicle Collisions: A Secondary Analysis of the CRASH Injury Study

Cited by 18 publications

References 38 publications

Genes known to escape X chromosome inactivation predict co‐morbid chronic musculoskeletal pain and posttraumatic stress symptom development in women following trauma exposure

Genes known to escape X chromosome inactivation predict co‐morbid chronic musculoskeletal pain and posttraumatic stress symptom development in women following trauma exposure

Epidemiology and 12-Month Outcomes of Patients Managed in a Thoracolumbosacral Orthosis After Trauma

Repeated Closed-Head Mild Traumatic Brain Injury Induces Robust Caspase-1 Mediated Inflammation that Contributes to Nociplastic Pain.

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