Sensory-motor response elicited by first time intraoral administered ethanol after trigeminal neuropathic injury.

Recent findings have shown a relationship between alcohol use disorders (AUD) and chronic pain. Preclinical models have demonstrated that chronic pain, including trigeminal nerve injury, increases ethanol consumption throughout extended administration periods. Nevertheless, it remains unclear whether chronic pain induces a greater susceptibility to developing AUD by altering motor control consumption regardless of the symptomatology of neuropathic pain, and whether sex influences this susceptibility. We used a former prolonged pain experience model induced by a constriction of the mental nerve (mNC) to answer this question. We analyzed ethanol consumption in a short-access protocol to reduce the post-ingestional effects and compared licking microstructure between groups. The constriction of the mental nerve induced evoked and spontaneous pain and reduction in the hedonic value of sucrose. The differences in alcohol consumption were not reflective of the former prolonged pain experience. Female mice showed a more efficient dynamic of consumption of alcohol, reflected in a long burst of licking and a less variable licking rate within a cluster.

Encoding signs of orofacial neuropathic pain from facial expressions in mice.

OBJECTIVE: To evaluate the effects of mental nerve injury in the facial reactions elicited by mechanical stimulation of different intensities and detect and quantify spontaneous facial pain-like expressions during a period free of stimuli, as signs of evoked and spontaneous pain in a mouse model for neuropathic orofacial pain. DESIGN: We recorded mouse heads in a fixed position during a stimulus-free period and with mechanical stimulation with 3 different Von Frey filaments. We extracted the Histograms of Oriented Gradients of each frame of the video recordings to be compared with a prototypical pain-like facial expression. The similarity score was then used to register and quantify the percentage of spontaneous pain-like facial reactions and evaluate the increased similarity to the prototypical pain-like face evoked by mechanical stimuli. The assessments were made one day before and four days after a unilateral mental nerve compression. RESULTS: Our findings show that mental nerve injury promotes an increase in spontaneous facial pain-like expressions and reduced mechanical threshold, reflected in a higher similarity to our pain-like face prototype, regardless of the intensity of the stimuli applied. CONCLUSIONS: Machine vision encodes the facial expression associated with evoked and spontaneous pain after mental nerve injury for up to four days. Facial expression quantitatively reflects the increased mechanical sensitivity elicited by mental nerve injury. We also show that this technique can detect spontaneous pain-like responses from facial reactions. Artificial vision can be applied to evaluate signs of orofacial neuropathic pain to study the involved neural circuits.

(Pro)renin/renin receptor expression during normal and preeclamptic pregnancy in rats.

AIMS: Pregnancy is a physiological stage with profound cardiovascular changes leading to hypotension. Preeclampsia (PE) reverts these normal changes inducing hypertension. Renin-angiotensin system (RAS) has been related in PE genesis. It has been reported a novel receptor in the system, the Prorenin/Renin receptor (PRR), with several roles in renal and cardiovascular illnesses. It is not known, however, if PRR changes its expression or is activated during normal or PE-complicated pregnancy on tissues intimately related to hypertension. So, the aim of this work was to describe PRR expression during normal and hypertensive pregnancy in rats. METHODS: We used a subrenal aortic coarctation (SRAC) model in rats. Atria, septum and ventricular heart tissue, aorta and renal tissue samples were homogenized and immunoblotted using anti-PRR and anti-PLZF antibodies. We also measured gene expression by RT-PCR. KEY FINDINGS: Hypertension and proteinuria were observed in SRAC-pregnant rats. In pregnant, non-SRAC rats, PRR showed a higher expression of both, gene and protein compared to non-pregnant rats in heart, aorta and kidney tissues. PE induces a very high expression of PRR in cardiac tissues and, on the contrary, decreases PRR expression in both, aorta and kidney. PLZF, a marker of PRR function, was augmented only in aorta and kidney in non-SRAC pregnant rats. In SRAC-pregnant rats, PLZF increment disappeared. SIGNIFICANCE: These findings indicate that PRR expression changes differently during pregnancy and PE in tissues related to cardiovascular functions and suggest a probable participation of the receptor during normal and preeclamptic pregnancy in the rat.

Three-dimensional structure and molecular dynamics studies of prorrenin/renin receptor: description of the active site.

The recent finding of a specific receptor for prorrenin/renin (PRR) has brought new insights into the physiology of the renin-angiotensin-aldosterone system. No undoubtable role has been described for this receptor so far. Its role seems to be important in chronic illnesses such as hypertension, possibly participating in the cardiovascular remodeling process, and diabetes where participation in inflammation development has been described. It is not possible, however, to explore the PRR function using classical pharmacological approaches due to the lack of specific agonists or antagonists. Two synthetic peptides have been described to accomplish these roles, but no conclusive data have been provided. There are no X-ray crystallography studies available to describe the structure and potential sites for drug development. So, the aim of this work was to model and theoretically describe the PRR. We describe and characterize the whole receptor protein, its spatial conformation and the potential interactions of PRR with the synthetic peptides available, describing the amino acid residues responsible for these interactions. This information provides the basis for directed development of drugs, seeking to agonize or antagonize PRR activity and study its function in health and ill stages.