Central sensitisation in chronic pain conditions: latest discoveries and their potential for precision medicine.

Chronic pain is a leading cause of disability globally and associated with enormous health-care costs. The discrepancy between the extent of tissue damage and the magnitude of pain, disability, and associated symptoms represents a diagnostic challenge for rheumatology specialists. Central sensitisation, defined as an amplification of neural signalling within the CNS that elicits pain hypersensitivity, has been investigated as a reason for this discrepancy. Features of central sensitisation have been documented in various pain conditions common in rheumatology practice, including fibromyalgia, osteoarthritis, rheumatoid arthritis, Ehlers-Danlos syndrome, upper extremity tendinopathies, headache, and spinal pain. Within individual pain conditions, there is substantial variation among patients in terms of presence and magnitude of central sensitisation, stressing the importance of individual assessment. Central sensitisation predicts poor treatment outcomes in multiple patient populations. The available evidence supports various pharmacological and non-pharmacological strategies to reduce central sensitisation and to improve patient outcomes in several conditions commonly seen in rheumatology practice. These data open up new treatment perspectives, with the possibility for precision pain medicine treatment according to pain phenotyping as a logical next step. With this view, studies suggest the possibility of matching non-pharmacological approaches, or medications, or both to the central sensitisation pain phenotypes.

Does repeated palpation-digitization of pelvic landmarks for measurement of innominate motion introduce a systematic error?--A psychometric investigation.

BACKGROUND: Palpation-digitization technique for measurement of innominate motion involves repeated manual palpation-digitization of pelvic landmarks, which could introduce a systematic variation between subsequent trials and thereby influence final innominate angular measurement. OBJECTIVES: The aim of this study is to quantify the effect of repeated palpation-digitization errors on overall variability of innominate vector length measurements; and to determine if there is a systematic variation between subsequent repeated trials. METHOD: A single group repeated measures study, using four testers and fourteen healthy participants, was conducted. Four pelvic landmarks, left and right posterior superior iliac spine and anterior superior iliac spine, were palpated and digitized using 3D digitizing stylus of Polhemus electromagnetic tracking device, for ten consecutive trials by each tester in their random order. The ten individual trials of innominate vector lengths measured by each tester for each participant were used for the analysis. RESULTS AND CONCLUSIONS: Repeated measures ANOVA demonstrated a very small effect of repeated trial factor (≤0.66%) as well as error component (≤0.32%) on innominate vector length variability. Further, residual versus order plots demonstrated a random pattern of errors across zero; thus indicating no systematic variation between subsequent trials of innominate vector length measurements.

Sequencing of T-superfamily conotoxins from Conus virgo: pyroglutamic acid identification and disulfide arrangement by MALDI mass spectrometry.

De novo mass spectrometric sequencing of two Conus peptides, Vi1359 and Vi1361, from the vermivorous cone snail Conus virgo, found off the southern Indian coast, is presented. The peptides, whose masses differ only by 2 Da, possess two disulfide bonds and an amidated C-terminus. Simple chemical modifications and enzymatic cleavage coupled with matrix assisted laser desorption ionization (MALDI) mass spectrometric analysis aided in establishing the sequences of Vi1359, ZCCITIPECCRI-NH(2), and Vi1361, ZCCPTMPECCRI-NH(2), which differ only at residues 4 and 6 (Z = pyroglutamic acid). The presence of the pyroglutamyl residue at the N-terminus was unambiguously identified by chemical hydrolysis of the cyclic amide, followed by esterification. The presence of Ile residues in both the peptides was confirmed from high-energy collision induced dissociation (CID) studies, using the observation of w(n)- and d(n)-ions as a diagnostic. Differential cysteine labeling, in conjunction with MALDI-MS/MS, permitted establishment of disulfide connectivity in both peptides as Cys2-Cys9 and Cys3-Cys10. The cysteine pattern clearly reveals that the peptides belong to the class of T-superfamily conotoxins, in particular the T-1 superfamily.