The Course of Serum Inflammatory Biomarkers Following Whiplash Injury and Their Relationship to Sensory and Muscle Measures: a Longitudinal Cohort Study

Tissue damage or pathological alterations are not detectable in the majority of people with whiplash associated disorders (WAD). Widespread hyperalgisa, morphological muscle changes and psychological distress are common features of WAD. However little is known about the presence of inflammation and its association with symptom persistence or the clinical presentation of WAD. This study aimed to prospectively investigate changes in serum inflammatory biomarker levels from the acute (<3 weeks) to chronic (>3 months) stages of whiplash injury. It also aimed to determine relationships between biomarker levels and hyperalgesia, fatty muscle infiltrates of the cervical extensors identified on MRI and psychological factors. 40 volunteers with acute WAD and 18 healthy controls participated. Participants with WAD were classified at 3 months as recovered/mild disability or having moderate/severe disability using the Neck Disability Index. At baseline both WAD groups showed elevated serum levels of CRP but by 3 months levels remained elevated only in the moderate/severe group. The recovered/mild disability WAD group had higher levels of TNF-α at both time points than both the moderate/severe WAD group and healthy controls. There were no differences found in serum IL-1β. Moderate relationships were found between hyperalgesia and CRP at both time points and between hyperalgesia and IL-1β 3 months post injury. There was a moderate negative correlation between TNF-α and amount of fatty muscle infiltrate and pain intensity at 3 months. Only a weak relationship was found between CRP and pain catastrophising and no relationship between biomarker levels and posttraumatic stress symptoms. The results of the study indicate that inflammatory biomarkers may play a role in outcomes following whiplash injury as well as being associated with hyperalgesia and fatty muscle infiltrate in the cervical extensors.     

Cervical helical axis characteristics and its center of rotation during active head and upper arm movements-comparisons of whiplash-associated disorders, non-specific neck pain and asymptomatic individuals

The helical axis model can be used to describe translation and rotation of spine segments. The aim of this study was to investigate the cervical helical axis and its center of rotation during fast head movements (side rotation and flexion/extension) and ball catching in patients with non-specific neck pain or pain due to whiplash injury as compared with matched controls. The aim was also to investigate correlations with neck pain intensity. A finite helical axis model with a time-varying window was used. The intersection point of the axis during different movement conditions was calculated. A repeated-measures ANOVA model was used to investigate the cervical helical axis and its rotation center for consecutive levels of 15 degrees during head movement. Irregularities in axis movement were derived using a zero-crossing approach. In addition, head, arm and upper body range of motion and velocity were observed. A general increase of axis irregularity that correlated to pain intensity was observed in the whiplash group. The rotation center was superiorly displaced in the non-specific neck pain group during side rotation, with the same tendency for the whiplash group. During ball catching, an anterior displacement (and a tendency to an inferior displacement) of the center of rotation and slower and more restricted upper body movements implied a changed movement strategy in neck pain patients, possibly as an attempt to stabilize the cervical spine during head movement.     

Energy Metabolic Changes in the Early Post-injury Period Following Traumatic Brain Injury in Rats

Impaired cerebral energy metabolism may be a major contributor to the secondary injury cascade that occurs following traumatic brain injury (TBI). To estimate the cortical energy metabolic state following mild and severe controlled cortical contusion (CCC) TBI in rats, ipsi-and contralateral cortical tissues were frozen in situ at 15 and 40 min post-injury and adenylate (ATP, ADP, AMP) levels were analyzed using high-performance liquid chromatography (HPLC) and the energy charge (EC) was calculated. At 15 min post-injury, mildly brain-injured animals showed a 43% decrease in cortical ATP levels and a 2.4-fold increase in AMP levels (P < 0.05), and there was a significant reduction of the ipsilateral cortical EC when compared to sham-injured animals (P < 0.05). At 40 min post-injury, the ipsilateral adenylate levels and EC had recovered to the values observed in the sham-injury group. In the severe CCC group, there was a 51% decrease in ipsilateral cortical ATP levels and a 5.3-fold increase in AMP levels with a significant reduction of cortical EC at 15 min post-injury (P < 0.05). At 40 min post-injury, a 2.6-fold ipsilateral increase in AMP levels and an 11% and 44% decrease in EC and ATP levels, respectively, remained (P < 0.05). A 37–38% reduction of the total adenylate pool was observed ipsilaterally in both CCC severity groups at the early time-point, and a 19% and 28% decrease remained in the mild and severe CCC groups, respectively, at 40 min post-injury. Significant contralateral ATP and EC changes were only observed in the severe CCC group at 40 min post-injury (P < 0.05). The energy-requiring secondary injury cascades that occur early post-injury do not challenge the brain tissue to the extent of ATP depletion and may provide a window of opportunity for therapeutic intervention.     

Whiplash injuries; diagnosis and treatment

Whiplash injury may extend far beyond the neck, and may involve even the soft tissues of the pelvis. For permanent recovery, all the injuries must be evaluated and treated together. When impact from the rear snaps the head back and then forward, posterior subluxations in the cervical spine cause anterior-posterior narrowing of the intervertebral foramina, which may result in injury to the cervical nerve roots. Impact at the front, causing hyperflexion followed by hyperextension, has a similar effect although usually not as severe. Resulting symptoms may not appear until two or three weeks later, when irritative lesions have developed because of hemorrhage or swelling. Mild or progressive degenerative changes may cause no symptoms but may predispose the affected area to injury following some slight trauma. Capsular ligaments of the lateral intervertebral joints are especially liable to whiplash injury which may give rise to scars and adhesions that compress spinal nerves. Sympathetic system involvement may cause reflex and referred pain. Detailed neurologic, roentgen and electromyographic studies may be necessary for proper evaluation of injuries. Seemingly psychosomatic pain or disability is likely to have some physical basis in whiplash injuries. In 33 patients with whiplash injury, some recently injured and some chronically disabled with persistent symptoms, good results were observed following hydromassage, hot packs, joint mobilization exercises and, in a few, cervical or pelvic traction.     

WHIPLASH INJURIES—Diagnosis and Treatment

Whiplash injury may extend far beyond the neck, and may involve even the soft tissues of the pelvis. For permanent recovery, all the injuries must be evaluated and treated together.When impact from the rear snaps the head back and then forward, posterior subluxations in the cervical spine cause anterior-posterior narrowing of the intervertebral foramina, which may result in injury to the cervical nerve roots. Impact at the front, causing hyperflexion followed by hyperextension, has a similar effect although usually not as severe. Resulting symptoms may not appear until two or three weeks later, when irritative lesions have developed because of hemorrhage or swelling. Mild or progressive degenerative changes may cause no symptoms but may predispose the affected area to injury following some slight trauma. Capsular ligaments of the lateral intervertebral joints are especially liable to whiplash injury which may give rise to scars and adhesions that compress spinal nerves. Sympathetic system involvement may cause reflex and referred pain.Detailed neurologic, roentgen and electromyographic studies may be necessary for proper evaluation of injuries. Seemingly psychosomatic pain or disability is likely to have some physical basis in whiplash injuries.In 33 patients with whiplash injury, some recently injured and some chronically disabled with persistent symptoms, good results were observed following hydromassage, hot packs, joint mobilization exercises and, in a few, cervical or pelvic traction.     

Masticatory muscle and temporomandibular joint pain in Croatian war veterans with posttraumatic stress disorder

The aim of this study was to investigate the prevalence and intensity of masticatory muscle and temporomandibular joint (TMJ) pain in Croatian war veterans with posttraumatic stress disorder (PTSD). The examined group consisted of 100 Croatian war veterans, in whom PTSD had previously been diagnosed. Patients were compared with 92 subjects who had not taken part in the war and in whom PTSD was excluded by psychiatric examination. The clinical examination consisted of palpation of the masticatory muscles, the prominent neck musculature, and TMJ. The examination technique used and the definition of items were previously tested for reliability and validity. 93% of the subjects with PTSD had masticatory muscle tenderness compared to 45.65% of the subjects in the control group (chi2 = 51.46, p < 0.0001). The most frequent painful location in the subjects with PTSD was the left lateral pterygoid site in 88%, and in subjects of the control group the right lateral pterygoid site in 28.26% of cases. The most painful location in the PTSD group was the left lateral pterygoid site in 72%, and in the control group the left posterior digastric in 4.35% of cases. 58% of the subjects with PTSD had TMJ tenderness compared to 3.26% of subjects in the control group (chi2 = 66.23, p < 0.0001). The most frequent painful location of TMJ in both groups was the left posterior capsule; in the PTSD group 38% and in subjects in the control group 2.17% of cases. The most painful location was the left posterior capsule in 28% of subjects with PTSD, while not one subject in the control group reported severe painful sensitivity. The very high frequency and intensity of pain in subjects with PTSD confirms the effect of stress on muscle and joint sensitivity, i.e. perception of pain.     

Haemodynamic changes in patients with whiplash injury measured by transcranial Doppler sonography (TCD)

The daily increasing number of cervical whiplash injuries presents ever-greater requirement for vertebrobasilar diagnostics. A cervical spine injury, which is quite frequent injury, may occur during a fall, or industrial, traffic, sport or war injury. Transcranial Doppler (TCD) sonography with Transcan 3-D EME device and 2 MHz probe was used for the assessment of vertebrobasilar circulation in patients with a whiplash injury of the cervical spine, that occurred mostly in car accident. This study includes 47 patients with clinically verified cervical spine trauma with x-ray evidence of no bone lesion. The patients were examined by TCD within a month, and then six months following the accident. The obtained values were compared to normal blood flow velocities and correlated with the severity of clinical picture. During the first month after the injury, statistically significant disturbances in the vertebrobasilar circulation were recorded, such as the increase in mean blood flow velocities in AVL (68%), AVR (62%) and BA (51%) (mostly as spasam). Six months later, normal findings were obtained in about 50% of the vessels, whereas in rest of the patients vasospasam persisted in one, two or all examined blood vessels. TCD of the vertebrobasilar circulation was found to be a very useful method in the diagnostics and follow-up of patients with a whiplash injury.     

Cervical spine vertebral and facet joint kinematics under whiplash.

Whiplash injuries sustained during a rear-end automobile collision have significant societal impact. The scientific literature on whiplash loading is both diverse and confusing. Definitive studies are lacking to describe the local mechanisms of injury that induce either acute or chronic pain symptoms. A methodology has been presented to quantify the kinematics of the cervical spine components by inducing controlled whiplash-type forces to intact human head-neck complexes. The localized facet joint kinematics and the overall segmental motions of the cervical spine are presented. It is anticipated that the use of this methodology will assist in a better delineation of the localized mechanisms of injury leading to whiplash pain.     

Specific and Evolving Resting-State Network Alterations in Post-Concussion Syndrome Following Mild Traumatic Brain Injury

Post-concussion syndrome has been related to axonal damage in patients with mild traumatic brain injury, but little is known about the consequences of injury on brain networks. In the present study, our aim was to characterize changes in functional brain networks following mild traumatic brain injury in patients with post-concussion syndrome using resting-state functional magnetic resonance imaging data. We investigated 17 injured patients with persistent post-concussion syndrome (under the DSM-IV criteria) at 6 months post-injury compared with 38 mild traumatic brain injury patients with no post-concussion syndrome and 34 healthy controls. All patients underwent magnetic resonance imaging examinations at the subacute (1–3 weeks) and late (6 months) phases after injury. Group-wise differences in functional brain networks were analyzed using graph theory measures. Patterns of long-range functional networks alterations were found in all mild traumatic brain injury patients. Mild traumatic brain injury patients with post-concussion syndrome had greater alterations than patients without post-concussion syndrome. In patients with post-concussion syndrome, changes specifically affected temporal and thalamic regions predominantly at the subacute stage and frontal regions at the late phase. Our results suggest that the post-concussion syndrome is associated with specific abnormalities in functional brain network that may contribute to explain deficits typically observed in PCS patients.     

单节段颈椎人工椎间盘置换术治疗颈椎病的临床研究

目的:探讨单节段颈椎人工椎间盘置换术(CDA)治疗颈椎病的临床效果。方法:选择2013年5月到2015年5月在我院收治的80例颈椎病患者,按手术方式不同分为颈椎人工椎间盘置换组(CDA组)和前路颈椎减压融合组(ACDF组),各40例。两组患者均于术前、术后3个月、术后6个月及术后1年进行末期随访时,采用颈椎功能障碍指数(NDI)评价患者颈部功能,采用颈痛视觉模拟评分(VAS)和上肢痛VAS评价患者颈部疼痛,采用X线片在过伸和过屈位测量患者术前和术后手术节段相邻节段的活动度。结果:两组患者术后3个月、6个月及术后1年时的NDI评分、颈痛VAS及上肢痛VAS均明显低于术前,差异具有统计学意义(P0.05),然而两组间比较差异无统计学意义(P0.05)。CDA组患者术后3个月、6个月及术后1年时的手术相邻上节段活动度和手术相邻下节段活动度与术前比较差异无统计学意义(P0.05),而ACDF组患者术后3个月、6个月及术后1年时均明显高于术前及同期CDA组,差异具有统计学意义(P0.05)。结论:单节段CDA治疗颈椎病的临床疗效与ACDF相近,另外其不会引起手术相邻节段活动度的增加,值得在临床上推广应用。     

Tensile cervical facet capsule ligament mechanics: failure and subfailure responses in the rat

Clinical, epidemiological, and biomechanical studies suggest the involvement of the cervical facet joint in neck pain. Mechanical studies have suggested the facet capsular ligament to be at risk for subfailure tensile injury during whiplash kinematics of the neck. Ligament mechanical properties can be altered by subfailure injury and such loading can induce cellular damage. However, at present, there is no clear understanding of the physiologic context of subfailure facet capsular ligament injury and mechanical implications for whiplash-related pain. Therefore, this study aimed to define a relationship between mechanical properties at failure and a subfailure condition associated with pain for tension in the rat cervical facet capsular ligament. Tensile failure studies of the C6/C7 rat cervical facet capsular ligament were performed using a customized vertebral distraction device. Force and displacement at failure were measured and stiffness and energy to failure were calculated. Vertebral motions and ligament deformations were tracked and maximum principal strains and their directions were calculated. Mean tensile force at failure (2.96 +/- 0.69 N) was significantly greater (p < 0.005) than force at subfailure (1.17 +/- 0.48 N). Mean ligament stiffness to failure was 0.75 +/- 0.27 N/mm. Maximum principal strain at failure (41.3 +/- 20.0%) was significantly higher (p = 0.003) than the corresponding subfailure value (23.1 +/- 9.3%). This study determined that failure and a subfailure painful condition were significantly different in ligament mechanics and findings provide preliminary insight into the relationship between mechanics and pain physiology for this ligament. Together with existing studies, these findings offer additional considerations for defining mechanical thresholds for painful injuries.     

Factors influencing recovery from headache after common whiplash.

OBJECTIVE--To assess the relation between pretraumatic and trauma related headache in patients suffering from whiplash. DESIGN--Follow up study of patients examined a mean (SD) of 7.4 (4.2) days after trauma and again at three and six months. SETTING--Patients referred from primary care. SUBJECTS--117 patients (mean age 30.8 (9.5) years. MAIN OUTCOME MEASURES--Prevalence of trauma related headache and the predictive relation by multiple logistic regression between different somatic and psychological variables and trauma related headache at each examination. RESULTS--Prevalence of trauma related headache decreased from 57% to 27%. History of pretraumatic headache proved a significant risk factor for presenting with trauma related headache. A significant relation between trauma related headache and the following variables was found: at seven days the initial wellbeing score, early onset of neck pain, depression scale from the personality inventory, and the initial intensity of neck pain; at three months, intensity of neck pain, and history of pretraumatic headache; and at six months neck pain, pain intensity, and history of pretraumatic headache. CONCLUSIONS--History of pretraumatic headache significantly increases the likelihood of presenting with trauma related headache but only in combination with findings indicative of clinically important injury to the cervical spine.     

Investigation of whiplash injuries in the upper cervical spine using a detailed neck model

Whiplash injuries continue to have significant societal cost; however, the mechanism and location of whiplash injury is still under investigation. Recently, the upper cervical spine ligaments, particularly the alar ligament, have been identified as a potential whiplash injury location. In this study, a detailed and validated explicit finite element model of a 50th percentile male cervical spine in a seated posture was used to investigate upper cervical spine response and the potential for whiplash injury resulting from vehicle crash scenarios. This model was previously validated at the segment and whole spine levels for both kinematics and soft tissue strains in frontal and rear impact scenarios. The model predicted increasing upper cervical spine ligament strain with increasing impact severity. Considering all upper cervical spine ligaments, the distractions in the apical and alar ligaments were the largest relative to their failure strains, in agreement with the clinical findings. The model predicted the potential for injury to the apical ligament for 15.2 g frontal or 11.7 g rear impacts, and to the alar ligament for a 20.7 g frontal or 14.4 g rear impact based on the ligament distractions. Future studies should consider the effect of initial occupant position on ligament distraction.     

Effects of abnormal posture on capsular ligament elongations in a computational model subjected to whiplash loading

Although considerable biomechanical investigations have been conducted to understand the response of the cervical spine under whiplash (rear impact-induced postero-anterior loading to the thorax), studies delineating the effects of initial spinal curvature are limited. This study advanced the hypothesis that abnormal curvatures (straight or kyphotic) of the cervical column affect spinal kinematics during whiplash loading. Specifically, compared to the normal lordotic curvature, abnormal curvatures altered facet joint ligament elongations. The quantifications of these elongations were accomplished using a validated mathematical model of the human head-neck complex that simulated three curvatures. The model was validated using companion experiments conducted in our laboratory that provided facet joint kinematics as a function of cervical spinal level. Regional facet joint ligament elongations were investigated as a function of whiplash loading in the four local anatomic regions of each joint. Under the normal posture, greatest elongations occurred in the dorsal anatomic region at the C2-C3 level and in the lateral anatomic region from C3-C4 to C6-C7 levels. Abnormal postures increased elongation magnitudes in these regions by up to 70%. Excessive ligament elongations induce laxity to the facet joint, particularly at the local regions of the anatomy in the abnormal kyphotic posture. Increased laxity may predispose the cervical spine to accelerated degenerative changes over time and lead to instability. Results from the present study, while providing quantified level- and region-specific kinematic data, concur with clinical findings that abnormal spinal curvatures enhance the likelihood of whiplash injury and may have long-term clinical and biomechanical implications.     

Prevalence of PTSD and Depression among Junior Middle School Students in a Rural Town Far from the Epicenter of the Wenchuan Earthquake in China

Context

On May12^th 2008, a devastating earthquake measuring 8.0 on the Richter scale, struck Wenchuan county and surrounding areas in China. The prevalence of mental illness among children and adolescents in a rural town far from the earthquake epicenter is unknown.

Objective

To assess the prevalence of posttraumatic stress disorder (PTSD) and depression among junior middle school students in a rural town Ningqiang county, 327 km from the earthquake epicenter.

Design, Setting, and Participants

A population-based mental health survey was conducted in March, 2009.

Main Outcome Measure

Survey Self-designed General Condition Survey Scale, Children''s Revised Impact of Event Scale (CRIES-13), and the Depression Self-rating Scale for Children (DSRSC) were used to sample 1,841 junior middle school students in Ningqiang county, ten months after the Wenchuan earthquake.

Results

The prevalence rate of a high-risk for PTSD was 28.4%, with 32.7% among females, 23.8% among males (female vs. male, p<0.001), 38.6% in the severe exposure group and 24.3% in the mild exposure group (severe vs. mild exposure, p<0.001). For depressive symptoms, the overall prevalence was 19.5%, with 24.0% among females, 14.7% among males, 24.5% in the severe exposure group and 17.5% in the mild exposure group (female vs. male, p<0.001; severe vs. mild exposure, p<0.001, respectively). In multivariate analysis, factors such as “having felt despair”, or “danger” and “having own house destroyed or damaged” were significantly associated with PTSD symptoms. Female gender and delayed evacuation in females, and earthquake related experiences in males were significantly associated with depression.

Conclusion

Traumatic events experienced during the earthquake were significantly associated with symptoms of PTSD and depression in children and adolescents, ten months after the Wenchuan earthquake. These data highlight a need for mental health services for children and adolescents in rural areas, far from earthquake epicenters.     

A Comparison of Health Outcomes in Older versus Younger Adults following a Road Traffic Crash Injury: A Cohort Study

Background

Given the aging demographics of most developed countries, understanding the public health impact of mild/moderate road traffic crash injuries in older adults is important. We aimed to determine whether health outcomes (pain severity and quality of life measures) over 24 months differ significantly between older (65+) and younger adults (18–64).

Methods

Prospective cohort study of 364, 284 and 252 participants with mild/moderate injury following a vehicle collision at baseline, 12 and 24 months, respectively. A telephone-administered questionnaire obtained information on socio-economic, pre- and post-injury psychological and heath characteristics.

Results

At baseline, there were 55 (15.1%) and 309 (84.9%) participants aged ≥65 and 18–64 years, respectively. At 12- and 24-month follow-up, older compared to younger participants who had sustained a mild/moderate musculoskeletal injury had lower physical functioning (3.9-units lower Short Form-12 Physical Composite Score, multivariable-adjusted p = 0.03 at both examinations). After multivariable adjustment, older (n = 45) versus younger (n = 207) participants had lower self-perceived health status (8.1-units lower European Quality of Life-5 Dimensions Visual Acuity Scale scores at 24 months, p = 0.03), 24 months later.

Conclusions

Older compared to younger participants who sustained a mild/moderate injury following a road-traffic crash demonstrated poorer physical functioning and general health at 24 months.     

Suprathreshold Heat Pain Response Predicts Activity-Related Pain,but Not Rest-Related Pain,in an Exercise-Induced Injury Model

Exercise-induced injury models are advantageous for studying pain since the onset of pain is controlled and both pre-injury and post-injury factors can be utilized as explanatory variables or predictors. In these studies, rest-related pain is often considered the primary dependent variable or outcome, as opposed to a measure of activity-related pain. Additionally, few studies include pain sensitivity measures as predictors. In this study, we examined the influence of pre-injury and post-injury factors, including pain sensitivity, for induced rest and activity-related pain following exercise induced muscle injury. The overall goal of this investigation was to determine if there were convergent or divergent predictors of rest and activity-related pain. One hundred forty-three participants provided demographic, psychological, and pain sensitivity information and underwent a standard fatigue trial of resistance exercise to induce injury of the dominant shoulder. Pain at rest and during active and resisted shoulder motion were measured at 48- and 96-hours post-injury. Separate hierarchical models were generated for assessing the influence of pre-injury and post-injury factors on 48- and 96-hour rest-related and activity-related pain. Overall, we did not find a universal predictor of pain across all models. However, pre-injury and post-injury suprathreshold heat pain response (SHPR), a pain sensitivity measure, was a consistent predictor of activity-related pain, even after controlling for known psychological factors. These results suggest there is differential prediction of pain. A measure of pain sensitivity such as SHPR appears more influential for activity-related pain, but not rest-related pain, and may reflect different underlying processes involved during pain appraisal.     

Cervical facet capsular ligament yield defines the threshold for injury and persistent joint-mediated neck pain

The cervical facet joint has been identified as a source of neck pain, and its capsular ligament is a likely candidate for injury during whiplash. Many studies have shown that the mechanical properties of ligaments can be altered by subfailure injury. However, the subfailure mechanical response of the facet capsular ligament has not been well defined, particularly in the context of physiology and pain. Therefore, the goal of this study was to quantify the structural mechanics of the cervical facet capsule and define the threshold for altered structural responses in this ligament during distraction. Tensile failure tests were preformed using isolated C6/C7 rat facet capsular ligaments (n=8); gross ligament failure, the occurrence of minor ruptures and ligament yield were measured. Gross failure occurred at 2.45+/-0.60 N and 0.92+/-0.17 mm. However, the yield point occurred at 1.68+/-0.56 N and 0.57+/-0.08 mm, which was significantly less than gross failure (p<0.001 for both measurements). Maximum principal strain in the capsule at yield was 80+/-24%. Energy to yield was 14.3+/-3.4% of the total energy for a complete tear of the ligament. Ligament yield point occurred at a distraction magnitude in which pain symptoms begin to appear in vivo in the rat. These mechanical findings provide insight into the relationship between gross structural failure and painful loading for the facet capsular ligament, which has not been previously defined for such neck injuries. Findings also present a framework for more in-depth methods to define the threshold for persistent pain and could enable extrapolation to the human response.     

Upregulation of Inflammatory Mediators in a Model of Chronic Pain after Spinal Cord Injury

Chronic neuropathic pain is a disabling condition observed in large number of individuals following spinal cord injury (SCI). Recent progress points to an important role of neuroinflammation in the pathogenesis of central neuropathic pain. The focus of the present study is to investigate the role of proinflammatory molecules IL-1β, TNF-α, MCP-1, MMP-9 and TIMP-1 in chronic neuropathic pain in a rodent model of SCI. Rats were subjected to spinal cord contusion using a controlled linear motor device with an injury epicenter at T10. The SCI rats had severe impairment in locomotor function at 7 days post-injury as assessed by the BBB score. The locomotor scores showed significant improvement starting at day 14 and thereafter showed no further improvement. The Hargreaves’ test was used to assess thermal hyperalgesia for hindpaw, forepaw and tail. A significant reduction in withdrawal latency was observed for forepaw and tail of SCI rats at days 21 and 28, indicating the appearance of thermal hyperalgesia. Changes in expression of mRNAs for IL-1β, TNF-α, MCP-1, MMP-9 and TIMP-1 were assessed using real-time polymerase chain reaction in spinal cord including the injury epicenter along with regions above and below the level of lesion at day 28 post-injury. A significant increase was observed in the expression of MCP-1, TNF-α, TIMP-1 and IL-1β in the injury epicenter, whereas only TIMP-1 was upregulated in the area below the injury epicenter. The results of the study suggest that prolonged upregulation of inflammatory mediators might be involved in chronic neuropathic pain in SCI, and that TIMP-1 may play a role in maintenance of chronic below level pain.     

Diffuse Brain Injury Induces Acute Post-Traumatic Sleep

Objective

Clinical observations report excessive sleepiness immediately following traumatic brain injury (TBI); however, there is a lack of experimental evidence to support or refute the benefit of sleep following a brain injury. The aim of this study is to investigate acute post-traumatic sleep.

Methods

Sham, mild or moderate diffuse TBI was induced by midline fluid percussion injury (mFPI) in male C57BL/6J mice at 9:00 or 21:00 to evaluate injury-induced sleep behavior at sleep and wake onset, respectively. Sleep profiles were measured post-injury using a non-invasive, piezoelectric cage system. In separate cohorts of mice, inflammatory cytokines in the neocortex were quantified by immunoassay, and microglial activation was visualized by immunohistochemistry.

Results

Immediately after diffuse TBI, quantitative measures of sleep were characterized by a significant increase in sleep (>50%) for the first 6 hours post-injury, resulting from increases in sleep bout length, compared to sham. Acute post-traumatic sleep increased significantly independent of injury severity and time of injury (9:00 vs 21:00). The pro-inflammatory cytokine IL-1β increased in brain-injured mice compared to sham over the first 9 hours post-injury. Iba-1 positive microglia were evident in brain-injured cortex at 6 hours post-injury.

Conclusion

Post-traumatic sleep occurs for up to 6 hours after diffuse brain injury in the mouse regardless of injury severity or time of day. The temporal profile of secondary injury cascades may be driving the significant increase in post-traumatic sleep and contribute to the natural course of recovery through cellular repair.