Mechanisms of Peripheral and Central Pain Sensitization: Focus on Ocular Pain

Persistent ocular pain caused by corneal inflammation and/or nerve injury is accompanied by significant alterations along the pain axis. Both primary sensory neurons in the trigeminal nerves and secondary neurons in the spinal trigeminal nucleus are subjected to profound morphological and functional changes, leading to peripheral and central pain sensitization. Several studies using animal models of inflammatory and neuropathic ocular pain have provided insight about the mechanisms involved in these maladaptive changes. Recently, the advent of new techniques such as optogenetics or genetic neuronal labelling has allowed the investigation of identified circuits involved in nociception, both at the spinal and trigeminal level. In this review, we will describe some of the mechanisms that contribute to the perception of ocular pain at the periphery and at the spinal trigeminal nucleus. Recent advances in the discovery of molecular and cellular mechanisms contributing to peripheral and central pain sensitization of the trigeminal pathways will be also presented

Does compression sensory axonopathy in the proximal tibia contribute to noncontact anterior cruciate ligament injury in a causative way?—a new theory for the injury mechanism

Anterior cruciate ligament injury occurs when the ligament fibers are stretched, partially torn, or completely torn. The authors propose a new injury mechanism for non-contact anterior cruciate ligament injury of the knee. Accordingly, non-contact anterior cruciate ligament injury could not happen without the acute compression microinjury of the entrapped peripheral proprioceptive sensory axons of the proximal tibia. This would occur under an acute stress response when con-comitant microcracks-fractures in the proximal tibia evolve due to the same excessive and repetitive compression forces. The primary damage may occur during eccentric contractions of the acceleration and deceleration moments of strenuous or unaccustomed fatiguing exercise bouts. This primary damage is suggested to be an acute compression/crush axonopathy of the proprioceptive sensory neurons in the proximal tibia. As a result, impaired proprioception could lead to injury of the anterior cruciate ligament as a secondary damage, which is suggested to occur during the deceleration phase. Elevated prostaglandin E2, nitric oxide and glutamate may have a critical neuro-modulatory role in the damage signaling in this dichotomous neuronal injury hypothesis that could lead to mechano-energetic failure, lesion and a cascade of inflammatory events. The presynaptic modulation of the primary sensory axons by the fatigued and microdamaged proprioceptive sensory fibers in the proximal tibia induces the activation of N-methyl-D-aspartate receptors in the dorsal horn of the spinal cord, through a process that could have long term relevance due to its contribution to synaptic plasticity. Luteinizing hormone, through interleukin-1β, stimulates the nerve growth factor-tropomyosin receptor kinase A axis in the ovarian cells and promotes tropomyosin receptor kinase A and nerve growth factor gene expression and prostaglandin E2 release. This luteinizing hormone induced mechanism could further elevate prostaglandin E2 in excess of the levels generated by osteocytes, due to mechanical stress during strenuous athletic moments in the pre-ovulatory phase. This may explain why non-contact anterior cruciate ligament injury is at least three-times more prevalent among female athletes

STUDY OF THE LEUKOCYTE MIGRATION INHIBITORY FACTOR IN HUMAN GLOMERULONEPHRITIS FROM THE ASPECT OF THE PROGNOSIS

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Влияние снижения кровотока в печени на артериальное давление и на ренин-ангиотензиновую систему крыс [Effect of decreased blood flow in the liver on blood pressure and on the renin-angiotensin system of the rat]

The effect of reduced blood flow in the liver was studied in acute and chronic experiments on rats. 2 hours after partial constriction of the portal vein in anesthetized rats the mean blood pressure was lower and the plasma renin activity higher than in the control group. There was no relation between the two parameters. 20 weeks after partial constriction of the portal vein in unanesthetized animals the body weight, liver weight and serum albumin fraction were decreased, while the kidney weight was increased significantly and the heart weight insignificantly. The systolic blood pressure of these animals was found to be lower than that of the controls, and their blood pressure response to the i. v. administration of angiotensin II was also lower. In comparison with the control no significant differences were found in the blood renin and substrate levels. The natriuresis proved considerably lower in the animals with the partial constriction of the portal vein