Accepted

Chronic visceral pain (CVP) is extremely difficult to diagnose, and available analgesic treatment options are quite limited. Identifying the proteins secreted from the colonic nociceptors, or their neighbor cells within the tube walls, in the context of disorders that course with visceral pain, might be useful to decipher the mechanism involved in the establishment of CVP. Addressing this question in human with gastrointestinal disorders entails multiple difficulties, as there is not a clear classification of disease severity, and colonic secretion is not easy to manage. We propose using of a murine model of colitis to identify new algesic molecules and pathways that could be explored as pain biomarkers or analgesia targets. Descending colons from naïve and colitis mice with visceral hyperalgesia were excised and maintained ex vivo. The proteins secreted in the perfusion fluid before and during acute noxious distension were evaluated using high-resolution mass spectrometry (MS). Haptoglobin (Hp), PZD and LIM domain protein 3 (Pdlim3), NADP-dependent malic enzyme (Me1), and Apolipoprotein A-I (Apoa1) were increased during visceral insult, whilst Triosephosphate isomerase (Tpi1), Glucose-6-phosphate isomerase (Gpi1), Alpha-enolase (Eno1), and Isoform 2 of Tropomyosin alpha-1 chain (Tpm1) were decreased. Most identified proteins have been described in the context of different chronic pain conditions and, according to gene ontology analysis, they are also involved in diverse biological processes of relevance. Thus, animal models that mimic human conditions in combination with unbiased omics approaches will ultimately help to identify new pathophysiological mechanisms underlying pain that might be useful in diagnosing and treating pain. Perspective Our study utilizes an unbiased proteomic approach to determine, first, the clinical relevance of a murine model of colitis and, second, to identify novel molecules/pathways involved in nociception that would be potential biomarkers or targets for chronic visceral pain.

Trigeminal neuralgia (TN) is a neuropathic pain that affects one or more branches of the trigeminal nerve. Surgical options after pharmacological failure are Microvascular Decompression (MVD) or percutaneous procedures, which include Balloon Compression (PBC). This study aims to describe pain outcomes and complications after PBC and MVD procedures for patients with trigeminal neuralgia.

Despite the pervasiveness of migraine, the underlying pathophysiological mechanisms initiating migraine attacks are far from well understood and are matter of scientific debate.

Ordinal data occur frequently in the social sciences. When applying principal component analysis (PCA), however, those data are often treated as numeric, implying linear relationships between the variables at hand; alternatively, non-linear PCA is applied where the obtained quantifications are sometimes hard to interpret. Non-linear PCA for categorical data, also called optimal scoring/scaling, constructs new variables by assigning numerical values to categories such that the proportion of variance in those new variables that is explained by a predefined number of principal components (PCs) is maximized. We propose a penalized version of non-linear PCA for ordinal variables that is a smoothed intermediate between standard PCA on category labels and non-linear PCA as used so far. The new approach is by no means limited to monotonic effects and offers both better interpretability of the non-linear transformation of the category labels and better performance on validation data than unpenalized non-linear PCA and/or standard linear PCA. In particular, an application of penalized optimal scaling to ordinal data as given with the International Classification of Functioning, Disability and Health (ICF) is provided.