Psychophysical Investigations into the Role of Low-Threshold C Fibres in Non-Painful Affective Processing and Pain Modulation

We recently showed that C low-threshold mechanoreceptors (CLTMRs) contribute to touch-evoked pain (allodynia) during experimental muscle pain. Conversely, in absence of ongoing pain, the activation of CLTMRs has been shown to correlate with a diffuse sensation of pleasant touch. In this study, we evaluated (1) the primary afferent fibre types contributing to positive (pleasant) and negative (unpleasant) affective touch and (2) the effects of tactile stimuli on tonic muscle pain by varying affective attributes and frequency parameters. Psychophysical observations were made in 10 healthy participants. Two types of test stimuli were applied: stroking stimulus using velvet or sandpaper at speeds of 0.1, 1.0 and 10.0 cm/s; focal vibrotactile stimulus at low (20 Hz) or high (200 Hz) frequency. These stimuli were applied in the normal condition (i.e. no experimental pain) and following the induction of muscle pain by infusing hypertonic saline (5%) into the tibialis anterior muscle. These observations were repeated following the conduction block of myelinated fibres by compression of sciatic nerve. In absence of muscle pain, all participants reliably linked velvet-stroking to pleasantness and sandpaper-stroking to unpleasantness (no pain). Likewise, low-frequency vibration was linked to pleasantness and high-frequency vibration to unpleasantness. During muscle pain, the application of previously pleasant stimuli resulted in overall pain relief, whereas the application of previously unpleasant stimuli resulted in overall pain intensification. These effects were significant, reproducible and persisted following the blockade of myelinated fibres. Taken together, these findings suggest the role of low-threshold C fibres in affective and pain processing. Furthermore, these observations suggest that temporal coding need not be limited to discriminative aspects of tactile processing, but may contribute to affective attributes, which in turn predispose individual responses towards excitatory or inhibitory modulation of pain

Comparative Study of Tumor Targeting and Biodistribution of pH (Low) Insertion Peptides (pHLIP® Peptides) Conjugated with Different Fluorescent Dyes

Purpose Acidification of extracellular space promotes tumor development, progression, and invasiveness. pH (low) insertion peptides (pHLIP® peptides) belong to the class of pH-sensitive membrane peptides, which target acidic tumors and deliver imaging and/or therapeutic agents to cancer cells within tumors. Procedures Ex vivo fluorescent imaging of tissue and organs collected at various time points after administration of different pHLIP® variants conjugated with fluorescent dyes of various polarity was performed. Methods of multivariate statistical analyses were employed to establish classification between fluorescently labeled pHLIP® variants in multidimensional space of spectral parameters. Results The fluorescently labeled pHLIP® variants were classified based on their biodistribution profile and ability of targeting of primary tumors. Also, submillimeter-sized metastatic lesions in lungs were identified by ex vivo imaging after intravenous administration of fluorescent pHLIP® peptide. Conclusions Different cargo molecules conjugated with pHLIP® peptides can alter biodistribution and tumor targeting. The obtained knowledge is essential for the design of novel pHLIP®-based diagnostic and therapeutic agents targeting primary tumors and metastatic lesions

A Functional Role for Modality-Specific Perceptual Systems in Conceptual Representations

Theories of embodied cognition suggest that conceptual processing relies on the same neural resources that are utilized for perception and action. Evidence for these perceptual simulations comes from neuroimaging and behavioural research, such as demonstrations of somatotopic motor cortex activations following the presentation of action-related words, or facilitation of grasp responses following presentation of object names. However, the interpretation of such effects has been called into question by suggestions that neural activation in modality-specific sensorimotor regions may be epiphenomenal, and merely the result of spreading activations from “disembodied”, abstracted, symbolic representations. Here, we present two studies that focus on the perceptual modalities of touch and proprioception. We show that in a timed object-comparison task, concurrent tactile or proprioceptive stimulation to the hands facilitates conceptual processing relative to control stimulation. This facilitation occurs only for small, manipulable objects, where tactile and proprioceptive information form part of the multimodal perceptual experience of interacting with such objects, but facilitation is not observed for large, nonmanipulable objects where such perceptual information is uninformative. Importantly, these facilitation effects are independent of motor and action planning, and indicate that modality-specific perceptual information plays a functionally constitutive role in our mental representations of objects, which supports embodied assumptions that concepts are grounded in the same neural systems that govern perception and action

High-Pitch, Low-Voltage and Low-Iodine-Concentration CT Angiography of Aorta: Assessment of Image Quality and Radiation Dose with Iterative Reconstruction

Objective: To assess the image quality of aorta obtained by dual-source computed tomography angiography (DSCTA), performed with high pitch, low tube voltage, and low iodine concentration contrast medium (CM) with images reconstructed using iterative reconstruction (IR). Methods: One hundred patients randomly allocated to receive one of two types of CM underwent DSCTA with the electrocardiogram-triggered Flash protocol. In the low-iodine group, 50 patients received CM containing 270 mg I/mL and were scanned at low tube voltage (100 kVp). In the high-iodine CM group, 50 patients received CM containing 370 mg I/mL and were scanned at the tube voltage (120 kVp). The filtered back projection (FBP) algorithm was used for reconstruction in both groups. In addition, the IR algorithm was used in the low-iodine group. Image quality of the aorta was analyzed subjectively by a 3-point grading scale and objectively by measuring the CT attenuation in terms of the signal- and contrast-to-noise ratios (SNR and CNR, respectively). Radiation and CM doses were compared.Results: The CT attenuation, subjective image quality assessment, SNR, and CNR of various aortic regions of interest did not differ significantly between two groups. In the low-iodine group, images reconstructed by FBP and IR demonstrated significant differences in image noise, SNR, and CNR (p<0.05). The low-iodine group resulted in 34.3% less radiation (4.4 ± 0.5 mSv) than the high-iodine group (6.7 ± 0.6 mSv), and 27.3% less iodine weight (20.36 ± 2.65 g) than the high-iodine group (28 ± 1.98 g). Observers exhibited excellent agreement on the aortic image quality scores (κ = 0.904). Conclusions: CT images of aorta could be obtained within 2 s by using a DSCT Flash protocol with low tube voltage, IR, and low-iodine-concentration CM. Appropriate contrast enhancement was achieved while maintaining good image quality and decreasing the radiation and iodine doses