Sensory bedside testing: a simple stratification approach for sensory phenotyping

Introduction: Stratification of patients according to the individual sensory phenotype has been suggested a promising method to identify responders for pain treatment. However, many state-of-the-art sensory testing procedures are expensive or time-consuming. Objectives: Therefore, this study aimed to present a selection of easy-to-use bedside devices. Methods: In total, 73 patients (39 m/34 f) and 20 controls (11 m/9 f) received a standardized laboratory quantitative sensory testing (QST) and a bedside-QST. In addition, 50 patients were tested by a group of nonexperienced investigators to address the impact of training. The sensitivity, specificity, and receiver-operating characteristics were analyzed for each bedside-QST parameter as compared to laboratory QST. Furthermore, the patients’ individual sensory phenotype (ie, cluster) was determined using laboratory QST, to select bedside-QST parameters most indicative for a correct cluster allocation. Results: The bedside-QST parameters “loss of cold perception to 22˚C metal,” “hypersensitivity towards 45˚C metal,” “loss of tactile perception to Q-tip and 0.7 mm CMS hair,” as well as “the allodynia sum score” indicated good sensitivity and specificity (ie, ≳70%). Results of interrater variability indicated that training is necessary for individual parameters (ie, CMS 0.7). For the cluster assessment, the respective bedside quantitative sensory testing (QST) parameter combination indicated the following agreements as compared to laboratory QST stratification: excellent for “sensory loss” (area under the curve [AUC] 5 0.91), good for “thermal hyperalgesia” (AUC 5 0.83), and fair for “mechanical hyperalgesia” (AUC 5 0.75). Conclusion: This study presents a selection of bedside parameters to identify the individual sensory phenotype as cost and time efficient as possible

The genetics of neuropathic pain from model organisms to clinical application

Neuropathic pain (NeuP) arises due to injury of the somatosensory nervous system and is both common and disabling, rendering an urgent need for non-addictive, effective new therapies. Given the high evolutionary conservation of pain, investigative approaches from Drosophila mutagenesis to human Mendelian genetics have aided our understanding of the maladaptive plasticity underlying NeuP. Successes include the identification of ion channel variants causing hyper-excitability and the importance of neuro-immune signaling. Recent developments encompass improved sensory phenotyping in animal models and patients, brain imaging, and electrophysiology-based pain biomarkers, the collection of large well-phenotyped population cohorts, neurons derived from patient stem cells, and high-precision CRISPR generated genetic editing. We will discuss how to harness these resources to understand the pathophysiological drivers of NeuP, define its relationship with comorbidities such as anxiety, depression, and sleep disorders, and explore how to apply these findings to the prediction, diagnosis, and treatment of NeuP in the clinic

The structure of the cushions in the feet of African elephants (Loxodonta africana)

The uniquely designed limbs of the African elephant, Loxodonta africana, support the weight of the largest terrestrial animal. Besides other morphological peculiarities, the feet are equipped with large subcutaneous cushions which play an important role in distributing forces during weight bearing and in storing or absorbing mechanical forces. Although the cushions have been discussed in the literature and captive elephants, in particular, are frequently affected by foot disorders, precise morphological data are sparse. The cushions in the feet of African elephants were examined by means of standard anatomical and histological techniques, computed tomography (CT) and magnetic resonance imaging (MRI). In both the forelimb and the hindlimb a 6th ray, the prepollex or prehallux, is present. These cartilaginous rods support the metacarpal or metatarsal compartment of the cushions. None of the rays touches the ground directly. The cushions consist of sheets or strands of fibrous connective tissue forming larger metacarpal/metatarsal and digital compartments and smaller chambers which were filled with adipose tissue. The compartments are situated between tarsal, metatarsal, metacarpal bones, proximal phalanges or other structures of the locomotor apparatus covering the bones palmarly/plantarly and the thick sole skin. Within the cushions, collagen, reticulin and elastic fibres are found. In the main parts, vascular supply is good and numerous nerves course within the entire cushion. Vater–Pacinian corpuscles are embedded within the collagenous tissue of the cushions and within the dermis. Meissner corpuscles are found in the dermal papillae of the foot skin. The micromorphology of elephant feet cushions resembles that of digital cushions in cattle or of the foot pads in humans but not that of digital cushions in horses. Besides their important mechanical properties, foot cushions in elephants seem to be very sensitive structures