scholarly journals Interactions of Peripheral Endothelin-1 and Nerve Growth Factor as Contributors to Persistent Cutaneous Pain

2018 ◽  
pp. S215-S225
Author(s):  
A. KHODOROVA ◽  
Y. ZHANG ◽  
G. NICOL ◽  
G. STRICHARTZ

Endothelin-1 (ET-1) and Nerve Growth Factor (NGF) are proteins, released from cancer-ridden tissues, which cause spontaneous pain and hypersensitivity to noxious stimuli. Here we examined the electrophysiological and behavioral effects of these two agents for evidence of their interactions. Individual small-medium cultured DRG sensory neurons responded to both ET-1 (50 nM, n=6) and NGF (100 ng/ml, n=4), with increased numbers of action potentials and decreased slow K+ currents; pre-exposure to ET-1 potentiated NGF´s actions, but not vice versa. Behaviorally, single intraplantar (i.pl.) injection of low doses of ET-1 (20 pmol) or NGF (100 ng), did not increase hindpaw tactile or thermal sensitivity, but their simultaneous injections sensitized the paw to both modalities. Daily i.pl. injections of low ET-1 doses in male rats caused tactile sensitization after 21 days, and enabled further tactile and thermal sensitization from low dose NGF, in ipsilateral and contralateral hindpaws. Single injections of 100 ng NGF, without changing the paw’s tactile sensitivity by itself, acutely sensitized the ipsilateral paw to subsequent injections of low ET-1. The sensitization from repeated low ET-1 dosing and the cross-sensitization between NGF and ET-1 were both significantly greater in female than in male rats. These findings reveal a synergistic interaction between cutaneously administered low doses of NGF and ET-1, which could contribute to cancer-related pain.

1997 ◽  
Vol 11 (3) ◽  
pp. 185-200 ◽  
Author(s):  
Bared Safieh-Garabedian ◽  
Salim A. Kanaan ◽  
Raffy H. Jalakhian ◽  
Suhayl J. Jabbur ◽  
Nayef E. Saadé

2005 ◽  
Vol 22 (8) ◽  
pp. 933-937 ◽  
Author(s):  
ChunMei Li ◽  
Gen Watanabe ◽  
Qiang Weng ◽  
WanZhu Jin ◽  
Chie Furuta ◽  
...  

1996 ◽  
Vol 76 (5) ◽  
pp. 3593-3596 ◽  
Author(s):  
A. Rueff ◽  
L. M. Mendell

1. Perfusion of the receptive field (RF) of C- or A delta-fiber nociceptors with nerve growth factor (NGF) in an in vitro preparation of the rat saphenous nerve with functionally attached skin induced a significant decrease in heat threshold without changing mechanical or cold sensitivity. 2. NGF-induced thermal sensitization was absent after saline perfusion and in skin taken from mast-cell depleted animals, hence confirming a role for mast cells in NGF-induced thermal hyperalgesia. 3. Neurotrophin-5 (NT-5) also induced a small but significant reduction in heat threshold without affecting mechanical sensitivity. It is speculated that NT-5 exerts its action either directly on the trkA receptor, as with NGF or alternatively through trkB receptors located on sympathetic efferents or on small diameter afferents.


2014 ◽  
Vol 112 (9) ◽  
pp. 2275-2282 ◽  
Author(s):  
Hayes Wong ◽  
Xu-Dong Dong ◽  
Brian E. Cairns

Intramuscular injection of nerve growth factor (NGF) into rat masseter muscle induces a local mechanical sensitization that is greater in female than in male rats. The duration of NGF-induced sensitization in male and female rats was associated with an increase in peripheral N-methyl-d-aspartate (NMDA) receptor expression by masseter muscle afferent fibers that began 3 days postinjection. Here, we investigated the functional consequences of increased NMDA expression on the response properties of masseter muscle mechanoreceptors. In vivo extracellular single-unit electrophysiological recordings of trigeminal ganglion neurons innervating the masseter muscle were performed in anesthetized rats 3 days after NGF injection (25 μg/ml, 10 μl) into the masseter muscle. Mechanical activation threshold was assessed before and after intramuscular injection of NMDA. NMDA injection induced mechanical sensitization in both sexes that was increased significantly following NGF injection in the male rats but not in the female rats. However, in female but not male rats, further examination found that preadministration of NGF induced a greater sensitization in slow Aδ-fibers (2–7 m/s) than fast Aδ-fibers (7–12 m/s). This suggests that preadministration of NGF had a different effect on slowly conducting mechanoreceptors in the female rats compared with the male rats. Although previous studies have found an association between estrogenic tone and NMDA activity, no correlation was observed between NMDA-evoked mechanical sensitization and plasma estrogen level. This study suggests NGF alters NMDA-induced mechanical sensitization in the peripheral endings of masseter mechanoreceptors in a sexually dimorphic manner.


2003 ◽  
Vol 181 (2) ◽  
pp. 301-312 ◽  
Author(s):  
Heather A Bimonte-Nelson ◽  
Rachel S Singleton ◽  
Matthew E Nelson ◽  
Christopher B Eckman ◽  
John Barber ◽  
...  

2021 ◽  
Author(s):  
Imane Lejri ◽  
Amandine Grimm ◽  
Pascal Trempat ◽  
Naoual Boujedaini ◽  
Anne Eckert

Abstract Background: Gelsemium sempervirens (GS) is a traditional medicinal plant, described at ultra-low doses as a remedy for a variety of psychological and behavioral symptoms of anxiety and depression. Changes in neural plasticity have been shown to play a significant role in the onset and development of those mental illnesses. Mitochondria play an extremely important role in the central nervous system by being the main energy producer through the oxidative phosphorylation and being involved particularly in the regulation of cell survival or death, as well as synaptic plasticity. Neurite outgrowth is the differentiation process by which neurons establish synapses through the protrusion of neurons and their extension. Methods: Because the effects of GS dilutions on mitochondrial function and neuroplasticity remain elusive, we aimed to investigate whether a treatment with GS at low doses (centesimal dilutions, C) improved bioenergetics parameters such as ATP production, mitochondrial respiration as well as cellular glycolysis before to characterize its effects on neurite outgrowth. Nerve growth factor (NGF), which is known as a promotor of cell growth and survival, was used as a positive control. Results: Our results demonstrate that GS dilutions (3C and 5C) efficiently ameliorated the bioenergetics of SH-SY5Y neuroblastoma cells by increasing cellular ATP level and mitochondrial respiration as well as promoting the cell survival. In addition, GS dilutions significantly improved neurite extension in the 2D as well as 3D culture model after 3 days of treatment. 3C and 5C dilutions showed similar functional effects than those obtained with the positive control nerve growth factor (NGF). Conclusions: These findings indicate that GS dilutions modulate the mitochondrial bioenergetic phenotype and improve the neurite formation. The mitochondrial function improving properties of GS dilutions might represent one possible important pathway contributing to its neuroprotective effectiveness. Key words: Gelsemium dilutions, mitochondria, bioenergetics, neurite outgrowth.


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