Novel Methods for Clinical Assessment of Nociception

Pain is a leading cause of morbidity in neuro-orthopaedic conditions, and remains an unmet clinical need. In this study, I aimed to advance the assessment of the pain states using novel objective methods in patients with neuro-orthopaedic disorders, and to develop biomarkers that could be useful in clinical trials of new therapies. Quantitative sensory testing, the current method of assessment of small fibre (nociceptor) function, was compared to novel objective methods including skin biopsy, contact heat evoked potentials (CHEPS) and functional magnetic resonance imaging (fMRI), in human volunteer models and patients. The clinical conditions studied were congenital insensitivity to pain presenting as orthopaedic disorders, complex regional pain syndrome, osteoarthritis, small-fibre pain syndromes, nerve and spinal root injuries. Cutaneous sensitisation biomarkers and mechanisms were identified in topical capsaicin pain models in human volunteers with study of skin biopsies, contact heat and laser evoked cerebral potentials, and fMRI. The models showed features observed in patients with neurogenic hypersensitivity, including hypersensitivity associated with regenerating nerve fibres. In patient groups, congenital insensitivity of pain patients showed absent CHEPS and lack of intra-epidermal nerve fibres, a novel finding. In patient groups with pain / hypersensitivity, CHEPS distinguished neuropathic from inflammatory mechanisms, while skin biopsies showed changes in nerve fibre density, particularly of nerve fibres positive for GAP43, a marker of regenerating nerve fibres, and of TRPV1, the heat and capsaicin receptor. As these changes require p38 MAP kinase activation in neurons, an inhibitor of p38MAP kinase was studied in a neuropathic pain clinical trial, which showed efficacy and support of the biomarkers. fMRI studies showed increased activation in regions of the brain associated with pain processing in the capsaicin model and painful osteoarthritis affecting the hand. These findings advance the assessment and understanding of pain disorders, and provide biomarkers for the development of new analgesics

Age Related Incidence and Early Outcomes of Hip Fractures: A Prospective Cohort Study of 1177 patients

<p>Abstract</p> <p>Introduction</p> <p>Associated with the increase in the aging population, there is an increase in the incidence of hip fractures worldwide. Outcome following such fractures is affected by age of the patient. This study aims to assess the incidence and early outcome of hip fractures, comparing between different age groups.</p> <p>Methods</p> <p>Data of hip fractures collected over a period of five years was analysed. Patients were divided into three groups, group A (patients under the age of 64), group B (patients between 65 and 84 years of age), and group C (patients over the age of 85).</p> <p>Results</p> <p>Of the 1177 patients included in the study, there were 90 patients in group A, 702 patients in group B and 385 patients in group C. There was a female preponderance across all age groups, and this increased as age advanced (p < 0.0001). A significantly larger number of older patients lived alone and needed aids to walk before the injury (p < 0.0001). There was no significant difference in the type of fracture across the three groups (p = 0.13). A higher proportion of the elderly with intracapsular fractures were treated by replacement arthroplasty. Older patients who had internal fixation of intracapsular fractures had a better walking ability at 4 months. The overall deterioration in mobility was greater in older patients (p < 0.0001). Mortality was higher in older patients.</p> <p>Conclusions</p> <p>Hip fractures are more common among females irrespective of age group. Older patients have a higher mortality and a greater deterioration of walking ability after such injuries. Internal fixation of intracapsular fractures have demonstrated satisfactory early outcome in the immediate period. This could be attributed to retention of native bone, better propioception and shorter operation time.</p

Functional MRI brain imaging studies using the Contact Heat Evoked Potential Stimulator (CHEPS) in a human volunteer topical capsaicin pain model

Acute application of topical capsaicin produces spontaneous burning and stinging pain similar to that seen in some neuropathic states, with local hyperalgesia. Use of capsaicin applied topically or injected intradermally has been described as a model for neuropathic pain, with patterns of activation in brain regions assessed using functional magnetic resonance imaging (fMRI) and positron emission tomography. The Contact Heat Evoked Potential Stimulator (CHEPS) is a noninvasive clinically practical method of stimulating cutaneous A-delta nociceptors. In this study, topical capsaicin (1%) was applied to the left volar forearm for 15 minutes of twelve adult healthy human volunteers. fMRI scans and a visual analog pain score were recorded during CHEPS stimulation precapsaicin and postcapsaicin application. Following capsaicin application there was a significant increase in visual analog scale (mean ± standard error of the mean; precapsaicin 26.4 ± 5.3; postcapsaicin 48.9 ± 6.0; P < 0.0001). fMRI demonstrated an overall increase in areas of activation, with a significant increase in the contralateral insular signal (mean ± standard error of the mean; precapsaicin 0.434 ± 0.03; postcapsaicin 0.561 ± 0.07; P = 0.047). The authors of this paper recently published a study in which CHEPS-evoked A-delta cerebral potential amplitudes were found to be decreased postcapsaicin application. In patients with neuropathic pain, evoked pain and fMRI brain responses are typically increased, while A-delta evoked potential amplitudes are decreased. The protocol of recording fMRI following CHEPS stimulation after topical application of capsaicin could be combined with recording of evoked potentials to provide a simple, rapid, and robust volunteer model to develop novel drugs for neuropathic pain

Lateral Clavicular Autograft for Repair of Reverse Hill-Sachs Defect

Posterior dislocations of the shoulder joint can result in an impression fracture over the anteromedial humeral head, termed the reverse Hill-Sachs lesion, the presence of which can contribute to recurrent dislocations. Methods described to repair this defect include using allografts, iliac crest and coracoid process autografts, and bone graft substitutes. We describe a novel technique using the lateral end of the ipsilateral clavicle as an autograft in a 78 year old man with a reverse Hill Sachs lesion. This graft can be harvested through the same incision and does not compromise the stability of the acromioclavicular joint or any future shoulder arthroplasty

Contact heat evoked potentials using simultaneous EEG and fMRI and their correlation with evoked pain

BACKGROUND: The Contact Heat Evoked Potential Stimulator (CHEPS) utilises rapidly delivered heat pulses with adjustable peak temperatures to stimulate the differential warm/heat thresholds of receptors expressed by Adelta and C fibres. The resulting evoked potentials can be recorded and measured, providing a useful clinical tool for the study of thermal and nociceptive pathways. Concurrent recording of contact heat evoked potentials using electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) has not previously been reported with CHEPS. Developing simultaneous EEG and fMRI with CHEPS is highly desirable, as it provides an opportunity to exploit the high temporal resolution of EEG and the high spatial resolution of fMRI to study the reaction of the human brain to thermal and nociceptive stimuli. METHODS: In this study we have recorded evoked potentials stimulated by 51° C contact heat pulses from CHEPS using EEG, under normal conditions (baseline), and during continuous and simultaneous acquisition of fMRI images in ten healthy volunteers, during two sessions. The pain evoked by CHEPS was recorded on a Visual Analogue Scale (VAS). RESULTS: Analysis of EEG data revealed that the latencies and amplitudes of evoked potentials recorded during continuous fMRI did not differ significantly from baseline recordings. fMRI results were consistent with previous thermal pain studies, and showed Blood Oxygen Level Dependent (BOLD) changes in the insula, post-central gyrus, supplementary motor area (SMA), middle cingulate cortex and pre-central gyrus. There was a significant positive correlation between the evoked potential amplitude (EEG) and the psychophysical perception of pain on the VAS. CONCLUSION: The results of this study demonstrate the feasibility of recording contact heat evoked potentials with EEG during continuous and simultaneous fMRI. The combined use of the two methods can lead to identification of distinct patterns of brain activity indicative of pain and pro-nociceptive sensitisation in healthy subjects and chronic pain patients. Further studies are required for the technique to progress as a useful tool in clinical trials of novel analgesics

Detection of human papilloma virus in potentially malignant and malignant lesions of the oral cavity and a study of associated risk factors

Background: Squamous cell carcinoma of the head and neck is the 6 th most frequently occurring cancer worldwide, with over 400,000 cases projected annually. Multiple factors such as tobacco, alcohol, irradiation, virus, and chronic irritants are involved in the development of oral squamous cell carcinomas (OSCCs). The most important risk factors are chronic exposure to tobacco and alcohol. Although the evidence that implicates virus is increasing, particularly (human papillomavirus [HPV]), in the carcinogenesis process, the role of virus is not well established. Aim and Objective: This study is designed to assess the presence of HPV in potentially malignant and malignant lesions of the oral cavity as well as to correlate the presence of HPV with addictive habits and histopathological grading of the disease. Materials and Methods: Biopsy samples of OSCC and potentially malignant lesions were obtained and 3, 5 μm thickness sections were cut using a microtome. The sections were collected using a sterile brush and transferred to an Eppendorf tube. DNA extraction and polymerase chain reaction for the detection of HPV were done. Results and Conclusion: The association between histopathological grading and presence of HPV was assessed using Chi-square test and the values thus obtained were found to be statistically significant. HPV was more predominantly seen in well-differentiated carcinomas and moderately differentiated carcinomas as compared to poorly differentiated carcinomas

Morphological Assessment of TMJ Spaces, Mandibular Condyle, and Glenoid Fossa Using Cone Beam Computed Tomography (CBCT): A Retrospective Analysis

Background The temporomandibular joint (TMJ) is included in the category of ginglymoarthrodial synovial joints. The mandibular condyle plays a vital part in the development of the craniofacial complex. Hence, the evaluation and assessment of the condylar volume and its morphology are of utmost importance. Aim The aim of this research was to use cone beam computed tomography (CBCT) imaging modality to evaluate the morphology of the mandibular condyle and glenoid fossa in a selected population and document any morphometric changes. Setting and Design It is an observational study. Materials and Methods A retrospective CBCT analysis was performed on 119 patients. The length, width, height, linear measurements of the joint spaces (anterior, posterior, and superior), volume of the condyle, and roof of glenoid fossa thickness were evaluated on both the left and right sides in both males and females. Results The height, width, and length of mandibular condyle were significantly increased in males on both sides. Except for the left anterior space, all other spaces were significantly larger in males. Overall, the volume of the condyles in males was significantly increased on both sides. Conclusion CBCT can be a valuable diagnostic aid in the evaluation of various dimensions, joint spaces, and condylar volume in different planes and thus, can be a useful predictor in the assessment of treatment outcomes of disorders affecting the TMJ