Minireview: Peripheral Nesfatin-1 in Regulation of the Gut Activity–15 Years since the Discovery

Nesfatin-1, discovered in 2006, is an anorexigenic molecule derived from the precursor protein NEFA/nucleobindin2. It is generally postulated that this molecule acts through a specific G protein-coupled receptor, as yet unidentified. Research conducted over the last 15 years has revealed both central and peripheral actions of nesfatin-1. Given its major central role, studies determining its inhibitory effect on food intake seem to be of major scientific interest. However, in recent years a number of experiments have found that peripheral organs, including those of the gastrointestinal tract (GIT), may also be a source (possibly even the predominant source) of nesfatin-1. This mini-review aimed to summarize the current state of knowledge regarding the expression and immunoreactivity of nesfatin-1 and its possible involvement (both physiological and pathological) in the mammalian GIT. Research thus far has shown very promising abilities of nesfatin-1 to restore the balance between pro-oxidants and antioxidants, to interplay with the gut microbiota, and to alter the structure of the intestinal barrier. This necessitates more extensive research on the peripheral actions of this molecule. More in-depth knowledge of such mechanisms (especially those leading to anti-inflammatory and anti-apoptotic effects) is important for a better understanding of the involvement of nefatin-1 in GIT pathophysiological conditions and/or for future therapeutic approaches.

Endothelin receptor type A is involved in the development of oxaliplatin-induced mechanical allodynia and cold allodynia acting through spinal and peripheral mechanisms in rats

Oxaliplatin, a platinum-based chemotherapeutic agent, frequently causes severe neuropathic pain typically encompassing cold allodynia and long-lasting mechanical allodynia. Endothelin has been shown to modulate nociceptive transmission in a variety of pain disorders. However, the action of endothelin varies greatly depending on many variables, including pain causes, receptor types (endothelin type A (ETA) and B (ETB) receptors) and organs (periphery and spinal cord). Therefore, in this study, we investigated the role of endothelin in a Sprague–Dawley rat model of oxaliplatin-induced neuropathic pain. Intraperitoneal administration of bosentan, a dual ETA/ETB receptor antagonist, effectively blocked the development or prevented the onset of both cold allodynia and mechanical allodynia. The preventive effects were exclusively mediated by ETA receptor antagonism. Intrathecal administration of an ETA receptor antagonist prevented development of long-lasting mechanical allodynia but not cold allodynia. In marked contrast, an intraplantar ETA receptor antagonist had a suppressive effect on cold allodynia but only had a partial and transient effect on mechanical allodynia. In conclusion, ETA receptor antagonism effectively prevented long-lasting mechanical allodynia through spinal and peripheral actions, while cold allodynia was prevented through peripheral actions.