A 10-day theta burst stimulation intervention facilitates the clinical rehabilitation of patients following an isolated limb fracture: A longitudinal SHAM-controlled pilot study.

OBJECTIVE: We investigated if theta burst stimulation (TBS) could enhance recovery by reducing key symptoms when implemented acutely post-fracture in participants with an isolated upper limb fracture (IULF). METHODS/DESIGN: This was a pilot study with a randomized matched pair, sham-controlled, participant-blind design of a 10-day prolonged continuous TBS protocol. Two main groups were included: I) participants with IULF receiving active TBS; and II) patients with IULF receiving SHAM/placebo. Another group (III) of healthy individuals were the reference group. Disability and pain intensity were collected through questionnaires (DASH & NRA) at three timepoints (baseline; 72 h post-intervention & 3 months post-injury). Group III completed the baseline assessment. RESULTS: 79 participants were enrolled. Individuals in the ACTIVE and SHAM groups had similar baseline measures. For disability, the interaction between Intervention and Time approached significance (F = 2.33; p = 0.11), whereas it was significant for pain (F = 3.42; p = 0.04). At 3 months post-injury, the ACTIVE group reported reduced disability (F = 4.71; p = 0.04) and pain (F = 5.84; p = 0.02) at three months post-injury compared to the SHAM group, with clinical measures from ACTIVE group being like controls. CONCLUSIONS: In IULF patients, a 10-day TBS intervention implemented acutely post-trauma had beneficial effects on symptoms of functional recovery and pain at 3 months post-trauma.

The Impact of Sleep Disturbances on Endogenous Pain Modulation: A Systematic Review and Meta-Analysis.

The bidirectional relationship between sleep and pain problems has been extensively demonstrated but despite all the accumulating evidence, their shared mechanisms are currently not fully understood. This review examined the association between sleep disturbances, defined as a broad array of sleep-related outcomes (eg, poor quality, short duration, insomnia), and endogenous pain modulation (EPM) in healthy and clinical populations. Our search yielded 6,151 references, and 37 studies met the eligibility criteria. Qualitative results showed mixed findings regarding the association between sleep disturbances and temporal summation of pain (TSP) and conditioned pain modulation (CPM), with poor sleep more commonly associated with decreased pain inhibition in both populations. Quantitative results indicated that such associations were not statistically significant, neither in healthy populations when EPM outcomes were assessed for changes pre-/post-sleep intervention (TSP: .31 [95%CI: -.30 to .92]; P = .321; CPM: .40 [95%CI: -.06 to .85] P = .088) nor in clinical populations when such association was assessed via correlation (TSP: -.00 [95%CI: -.22 to .21] P = .970; CPM: .12 [95%CI: -.05 to .29]; P = .181). For studies that reported results by sex, meta-analysis showed that experimental sleep disturbances impaired pain inhibition in females (1.43 [95%CI: .98-1.88]; P < .001) but not in males (-.30 [95%CI: -2.69 to 1.60]; P = .760). Only one study investigating the association between sleep disturbances and offset analgesia was identified, while no studies assessing spatial summation of pain were found. Overall, this review provides a comprehensive overview of the association between sleep disturbances and EPM function, emphasizing the need for further investigation to clarify specific mechanisms and phenotypic subtypes. PERSPECTIVE: This review shines a light on the association between sleep disturbances and endogenous pain modulation function. Qualitatively, we found a frequent association between reduced sleep quality and impaired pain inhibition. However, quantitatively such an association was not corroborated. Sex-specific effects were observed, with females presenting sleep-related impaired pain inhibition but not males.

Females with painful temporomandibular disorders present higher intracortical facilitation relative to pain-free controls.

OBJECTIVES: This study aimed to investigate cortical excitability differences in the primary motor cortex (M1) hand representation between individuals with temporomandibular disorders (TMD) and healthy controls. We assessed resting motor thresholds, motor-evoked potentials (MEPs), intracortical inhibition, and intracortical facilitation and explored potential associations with clinical and psychosocial characteristics in the TMD group. MATERIALS AND METHODS: We recruited 36 female participants with TMD and 17 pain-free controls. Transcranial magnetic stimulation (TMS) was used to assess M1 cortical excitability. Correlations between clinical and psychosocial factors and cortical excitability measures were also evaluated. RESULTS: Patients with TMD showed significantly higher intracortical facilitation at 12 ms (z = 1.98, p = 0.048) and 15 ms (z = 2.65, p = 0.008) when compared to controls. Correlations revealed associations between intracortical facilitation and pain interference, sleep quality, depressive symptoms, and pain catastrophizing in the TMD group. CONCLUSIONS: Females with TMD exhibit heightened motor cortex intracortical facilitation in the hand representation, potentially indicating altered cortical excitability beyond the motor face area. This suggests a role for cortical excitability in TMD pathophysiology, influenced by psychosocial factors. CLINICAL RELEVANCE: Understanding cortical excitability in TMD may inform targeted interventions. Psychosocial variables may play a role in cortical excitability, emphasizing the multidimensional nature of TMD-related pain. Further research is needed to confirm and expand upon these findings, with potential implications for the management of TMD and related pain conditions.

The Putative Role of Neuroinflammation in the Interaction between Traumatic Brain Injuries, Sleep, Pain and Other Neuropsychiatric Outcomes: A State-of-the-Art Review.

Sleep disturbances are widely prevalent following a traumatic brain injury (TBI) and have the potential to contribute to numerous post-traumatic physiological, psychological, and cognitive difficulties developing chronically, including chronic pain. An important pathophysiological mechanism involved in the recovery of TBI is neuroinflammation, which leads to many downstream consequences. While neuroinflammation is a process that can be both beneficial and detrimental to individuals' recovery after sustaining a TBI, recent evidence suggests that neuroinflammation may worsen outcomes in traumatically injured patients, as well as exacerbate the deleterious consequences of sleep disturbances. Additionally, a bidirectional relationship between neuroinflammation and sleep has been described, where neuroinflammation plays a role in sleep regulation and, in turn, poor sleep promotes neuroinflammation. Given the complexity of this interplay, this review aims to clarify the role of neuroinflammation in the relationship between sleep and TBI, with an emphasis on long-term outcomes such as pain, mood disorders, cognitive dysfunctions, and elevated risk of Alzheimer's disease and dementia. In addition, some management strategies and novel treatment targeting sleep and neuroinflammation will be discussed in order to establish an effective approach to mitigate long-term outcomes after TBI.

Relevance of Sleep Disturbances to Orthopaedic Surgery: A Current Concepts Narrative and Practical Review.

➤: Sleep disturbances can increase the risk of falls and motor vehicle accidents and may reduce bone density. ➤: Poor sleep can lead to worse outcomes after fracture, such as chronic pain and delayed recovery. ➤: Orthopaedic surgeons can play an important role in the screening of sleep disorders among their patients.

Subtle long-term cognitive effects of a single mild traumatic brain injury and the impact of a three-month aerobic exercise intervention.

BACKGROUND: Although there is a growing body of literature on the impact of multiple concussions on cognitive function with aging, less is known about the long-term impact of sustaining a single mild traumatic brain injury (mTBI). Additionally, very few interventions exist to treat mTBI patients and prevent a possible accelerated cognitive decline. This study aimed to: 1) examine the long-term effects of a single mTBI on cognition in patients aged between 55 and 70 years old; and 2) evaluate the cognitive effects of an aerobic exercise program for these patients. METHODS: Thirty-five participants (average age: 58.89, SD=4.14) were assessed using neuropsychological tests. Among them, 18 hadsustained a mTBI two to seven years earlier. Significant differences in information processing speed, executive function and visual memory were found between controls and mTBI patients. Sixteen of the mTBI patients then engaged in a 12-week physical exercise program. They were divided into equivalent groups: 1) aerobic training (cycle ergometers); or 2) stretching exercises. The participants' cardiopulmonary fitness (VO2max) was evaluated pre- and postintervention and neuropsychological tests were re-administered postintervention. RESULTS: Participants from the aerobic group significantly improved their fitness compared to the stretching group. However, no between-group difference was found on neuropsychological measures postintervention. CONCLUSIONS: In summary, this study shows long-term cognitive effects of mTBI in late adulthood patients. Moreover, the controlled, 12-week aerobic exercise program did not lead to cognitive improvements in our small mTBI sample. Lastly, future directions in optimizing mTBI intervention are discussed.

Moderate to severe acute pain disturbs motor cortex intracortical inhibition and facilitation in orthopedic trauma patients: A TMS study.

OBJECTIVE: Primary motor (M1) cortical excitability alterations are involved in the development and maintenance of chronic pain. Less is known about M1-cortical excitability implications in the acute phase of an orthopedic trauma. This study aims to assess acute M1-cortical excitability in patients with an isolated upper limb fracture (IULF) in relation to pain intensity. METHODS: Eighty-four (56 IULF patients <14 days post-trauma and 28 healthy controls). IULF patients were divided into two subgroups according to pain intensity (mild versus moderate to severe pain). A single transcranial magnetic stimulation (TMS) session was performed over M1 to compare groups on resting motor threshold (rMT), short-intracortical inhibition (SICI), intracortical facilitation (ICF), and long-interval cortical inhibition (LICI). RESULTS: Reduced SICI and ICF were found in IULF patients with moderate to severe pain, whereas mild pain was not associated with M1 alterations. Age, sex, and time since the accident had no influence on TMS measures. DISCUSSION: These findings show altered M1 in the context of acute moderate to severe pain, suggesting early signs of altered GABAergic inhibitory and glutamatergic facilitatory activities.

Investigating the incidence and magnitude of heterotopic ossification with and without joints involvement in patients with a limb fracture and mild traumatic brain injury.

OBJECTIVES: This study seeks to evaluate the incidence rate of heterotopic ossification (HO) formation in patients afflicted by an isolated limb fracture (ILF) and a concomitant mild traumatic brain injury (mTBI). METHODS: The current study is an observational study including ILF patients with or without a concomitant mTBI recruited from an orthopedic clinic of a Level 1 Trauma Hospital. Patients were diagnosed with a mTBI according to the American Congress of Rehabilitation Medicine (ACRM) criteria. Radiographs taken on average 3 months post-trauma were analyzed separately by two distinct specialists for the presence of HO proximally to the fracture site (joints or extra joints). Both raters referred to Brooker's and Della's Valle's classification to establish signs of HO. First, analyses were conducted for the full sample. Secondly, a matched cohort was used in order to control for specific factors, namely age, sex, type of injury, and time elapsed between the accident and the analyzed radiograph. RESULTS: The full sample included a total of 183 patients with an ILF (94 females; 47.5 years old), of which 50 had a concomitant mTBI and 133 without. Radiographic evidence of HO was significantly higher in patients with an ILF and a mTBI compared to ILF patients (X2 = 6.50; p = 0.01). The matched cohort consisted of 94 participants (i.e.; 47 patients from the ILF + mTBI group and 47 patients from the ILF group). Again, ILF + mTBI patients presented significantly higher rates of HO signs in comparison to ILF patients (X2 = 3.69; p = 0.04). Presence of HO was associated with prolonged delays to return to work (RTW) only in ILF + mTBI patients (F = 4.055; p = 0.05) but not in ILF patients (F = 0.823; p = 0.37). CONCLUSIONS: Study findings suggest that rates of HO are significantly higher proximally to fracture sites when ILF patients sustain a concomitant mTBI, even after controlling for factors known to influence HO. Moreover, results show that HO is associated with a prolonged RTW only in ILF patients with a concomitant mTBI but not in ILF-only patients. The impact of mTBI on HO formation warrants further attention to detect early signs of HO, to identify shared physiopathological mechanisms and, ultimately, to design targeted therapies.

The clinical utility of repetitive transcranial magnetic stimulation in reducing the risks of transitioning from acute to chronic pain in traumatically injured patients.

Pain is a multifaceted condition and a major ongoing challenge for healthcare professionals having to treat patients in whom pain put them at risk of developing other conditions. Significant efforts have been invested in both clinical and research settings in an attempt to demystify the mechanisms at stake and develop optimal treatments as well as to reduce individual and societal costs. It is now universally accepted that neuroinflammation and central sensitization are two key underlying factors causing pain chronification as they result from maladaptive central nervous system plasticity. Recent research has shown that the mechanisms of action of repetitive transcranial magnetic stimulation (rTMS) make it a particularly promising avenue in treating various pain conditions. This review will first discuss the contribution of neuroinflammation and central sensitization in the transition from acute to chronic pain in traumatically injured patients. A detailed discussion on how rTMS may allow the restoration from maladaptive plasticity in addition to breaking down the chain of events leading to pain chronification will follow. Lastly, this review will provide a theoretical framework of what might constitute optimal rTMS modalities in dealing with pain symptoms in traumatically injured patients based on an integrated perspective of the physiopathological mechanisms underlying pain.

Effects of concomitant mild traumatic brain injury on resuming work after suffering from an isolated limb fracture: A cohort study.

BACKGROUND: The objective is to explore the effects of concomitant mild traumatic brain injury (mTBI) on return to work (RTW), among patients suffering from an isolated limb fracture. This follow-up study included a total of 170 working age subjects with an isolated limb fracture, and was conducted in a phone interview approximately 1-year post trauma. 41 had experienced an mTBI and 129 did not. METHODS: Data were obtained through a phone interview conducted on average 20.7 months (SD = 9.6 months) post-accident. The main outcome measure was the number of days taken to RTW after the injury. Demographic information was also gathered during the phone interview. Workers' compensation status was obtained through the hospitals' orthopaedic clinic data. RESULTS: The mTBI group took on average 329.7 days (SD = 298.0) to RTW after the injury, as opposed to 150.3 days (SD = 171.3) for the control group (p < 0.001). After excluding patients who received workers' compensation, the mTBI group still missed significantly more days of work (M = 299.4 days; SD = 333.0) than the control group (M = 105.2 days; SD = 121.6) (p < 0.0001). CONCLUSION: This study shows that mTBI increases work disability by preventing working-age individuals from rapidly returning to work.

Comorbid mild traumatic brain injury increases pain symptoms in patients suffering from an isolated limb fracture.

OBJECTIVES: This study seeks to evaluate the effects of a mild traumatic brain injury (mTBI) on pain in patients with an isolated limb fracture (ILF) when compared to a matched cohort group with no mTBI (control group). PATIENTS AND METHODS: All subjects included in this observational study suffered from an ILF. Groups were matched according to the type of injury, sex, age, and time since the accident. Main outcome measurements were: Standardized semi-structured interviews at follow-up of a Level I Trauma Center, and a questionnaire on fracture-related pain symptoms. Factors susceptible to influence the perception of pain, such as age, sex, severity of post-concussive symptoms, and worker compensation were also assessed. RESULTS: A total of 68 subjects (36 females; 45 years old) with an ILF were selected, 34 with a comorbid mTBI and 34 without (24/34 with an upper limb fracture per group, 71% of total sample). Patients with mTBI and an ILF reported significantly higher pain scores at the time of assessment (mean: 49days, SD: 34.9), compared to the control group (p<0.0001; mean difference 2.8, 95% confidence interval 1.8-4.0). Correlational analyses show no significant association between the level of pain and factors such as age, sex, severity of post-concussive symptoms, and worker compensation. CONCLUSIONS: Results suggest that mTBI exacerbate perception of pain in the acute phase when occurring with an ILF, and were not explained by age, sex, post-concussive symptoms, or worker compensation. Rather, it appears possible that neurological sequelae induced by mTBI may interfere with the normal recovery of pain following trauma.

Incidence rate of mild traumatic brain injury among patients who have suffered from an isolated limb fracture: Upper limb fracture patients are more at risk.

OBJECTIVES: This study compares the incidence rate of mild traumatic brain injury (mild TBI) detected at follow-up visits (retrospective diagnosis) in patients suffering from an isolated limb trauma, with the incidence rate held by the hospital records (prospective diagnosis) of the sampled cohort. This study also seeks to determine which types of fractures present with the highest incidence of mild TBI. PATIENTS AND METHODS: Retrospective assessment of mild TBI among orthopaedic monotrauma patients, randomly selected for participation in an Orthopaedic clinic of a Level I Trauma Hospital. Patients in the remission phase of a limb fracture were recruited between August 2014 and May 2015. No intervention was done (observational study). MAIN OUTCOME MEASUREMENTS: Standardized semi-structured interviews were conducted with all patients to retrospectively assess for mild TBI at the time of the fracture. Emergency room related medical records of all patients were carefully analyzed to determine whether a prospective mild TBI diagnosis was made following the accident. RESULTS: A total of 251 patients were recruited (54% females, Mean age=49). Study interview revealed a 23.5% incidence rate of mild TBI compared to an incidence rate of 8.8% for prospective diagnosis (χ(2)=78.47; p<0.0001). Patients suffering from an upper limb monotrauma (29.6%; n=42/142) are significantly more at risk of sustaining a mild TBI compared to lower limb fractures (15.6%; n=17/109) (χ(2)=6.70; p=0.010). More specifically, patients with a proximal upper limb injury were significantly more at risk of sustaining concomitant mild TBI (40.6%; 26/64) compared to distal upper limb fractures (20.25%; 16/79) (χ(2)=7.07; p=0.008). CONCLUSIONS: Results suggest an important concomitance of mild TBI among orthopaedic trauma patients, the majority of which go undetected during acute care. Patients treated for an upper limb fracture are particularly at risk of sustaining concomitant mild TBI.