Identification of Potential Visceral Pain Biomarkers in Colon Exudates from Mice with Experimental Colitis: An Exploratory In Vitro Study.

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.

Zoonotic Microsporidia in Wild Lagomorphs in Southern Spain.

Microsporidia are obligate intracellular protist-like fungal pathogens that infect a broad range of animal species, including humans. This study aimed to assess the presence of zoonotic microsporidia (Enterocytozoon bieneusi, Encephalitozoon intestinalis, Encephalitozoon hellem, and Encephalitozoon cuniculi) in organ meats of European wild rabbit (Oryctolagus cuniculus) and Iberian hare (Lepus granatensis) consumed by humans in Spain. Between July 2015 and December 2018, kidney samples from 383 wild rabbits and kidney and brain tissues from 79 Iberian hares in southern Spain were tested by species-specific PCR for the detection of microsporidia DNA. Enterocytozoon bieneusi infection was confirmed in three wild rabbits (0.8%; 95% CI: 0.0-1.7%) but not in hares (0.0%; 95% CI: 0.0-4.6%), whereas E. intestinalis DNA was found in one wild rabbit (0.3%; 95% CI: 0.0-0.8%) and three Iberian hares (3.8%; 95% CI: 0.0-8.0%). Neither E. hellem nor E. cuniculi infection were detected in the 462 (0.0%; 95% CI: 0.0-0.8%) lagomorphs analyzed. The absence of E. hellem and E. cuniculi infection suggests a low risk of zoonotic foodborne transmission from these wild lagomorph species in southern Spain. To the authors' knowledge, this is the first report of E. intestinalis infection in wild rabbits and Iberian hares. The presence of E. bieneusi and E. intestinalis in organ meats from wild lagomorphs can be of public health concern. Additional studies are required to determine the real prevalence of these parasites in European wild rabbit and Iberian hare.