scholarly journals The causal role of magnesium deficiency in the neuroinflammation, pain hypersensitivity and memory/emotional deficits in ovariectomized and aging mice

2021 ◽  
Author(s):  
Xian-guo Liu ◽  
Jun Zhang ◽  
Chun-lin Mai ◽  
Ying Xiong ◽  
Zhen-Jia Lin ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Dorsal Root Ganglion ◽  
Dorsal Horn ◽  
Dorsal Root ◽  
Dorsal Root Ganglion Neurons ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Emotional Deficits ◽  
Ganglion Neurons ◽  
Neuronal Disorders

Abstract Background: Postmenopausal women often suffer from chronic pain, memory decline and mood depression. The mechanisms underlying the neuronal disorders are not fully understood and effective treatment is still lacking.Methods: Oral administration of magnesium-L-threonate was tested to treat the neuronal disorders in ovariectomized and aging mice. The pain hypersensitivity, memory function and depression were measured with a set of behavioral tests. Western blots and immunochemistry were used to assess molecular changes.Results: Chronic oral administration of magnesium-L-threonate substantially prevented or reversed the chronic pain, and memory/emotional deficits in both ovariectomized and aging female mice. We found that phospho-p65, an active form of nuclear factor-kappaB, tumor necrosis factor-alpha and interleukin-1beta were significantly upregulated in the neurons of dorsal root ganglion, spinal dorsal horn and hippocampus in ovariectomized and aging mice. The microglia and astrocytes were activated in spinal dorsal horn and hippocampus. The peptidergic C-fibers in dorsal horn were increased, which are associated with potentiation of C-fiber-mediated synaptic transmission in the model mice. In parallel with neuroinflammation and synaptic potentiation, free Mg2+ levels in plasma, cerebrospinal fluid and dorsal root ganglion neurons were significantly reduced. Oral magnesium-L-threonate normalized the neuroinflammation, synaptic potentiation and Mg2+ deficiency, but did not affect the estrogen decline in ovariectomized and aging mice. Furthermore, in cultured dorsal root ganglion neurons estrogen elevated intracellular Mg2+, and depressed the upregulation of phospho-p65, tumor necrosis factor-alpha and interleukin-1beta exclusively in the presence of extracellular Mg2+.Conclusions: Estrogen decline in menopause causes neuroinflammation by reducing intracellular Mg2+ in neurons, leading to chronic pain, memory/emotional deficits. Thus, supplement Mg2+ by oral magnesium-L-threonate may be a novel approach for treating menopause-related neuronal disorders.

scholarly journals TNF-α mediated upregulation of NaV1.7 currents in rat dorsal root ganglion neurons is independent of CRMP2 SUMOylation

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Flávio Henrique Pequeno de Macedo ◽  
Rosária Dias Aires ◽  
Esdras Guedes Fonseca ◽  
Renata Cristina Mendes Ferreira ◽  
Daniel Portela Dias Machado ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Diabetic Neuropathy ◽  
Dorsal Root ◽  
Sodium Current ◽  
Dorsal Root Ganglion Neurons ◽  
Drg Neurons ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Ganglion Neurons ◽  
Total Sodium

AbstractClinical and preclinical studies have shown that patients with Diabetic Neuropathy Pain (DNP) present with increased tumor necrosis factor alpha (TNF-α) serum concentration, whereas studies with diabetic animals have shown that TNF-α induces an increase in NaV1.7 sodium channel expression. This is expected to result in sensitization of nociceptor neuron terminals, and therefore the development of DNP. For further study of this mechanism, dissociated dorsal root ganglion (DRG) neurons were exposed to TNF-α for 6 h, at a concentration equivalent to that measured in STZ-induced diabetic rats that developed hyperalgesia. Tetrodotoxin sensitive (TTXs), resistant (TTXr) and total sodium current was studied in these DRG neurons. Total sodium current was also studied in DRG neurons expressing the collapsin response mediator protein 2 (CRMP2) SUMO-incompetent mutant protein (CRMP2-K374A), which causes a significant reduction in NaV1.7 membrane cell expression levels. Our results show that TNF-α exposure increased the density of the total, TTXs and TTXr sodium current in DRG neurons. Furthermore, TNF-α shifted the steady state activation and inactivation curves of the total and TTXs sodium current. DRG neurons expressing the CRMP2-K374A mutant also exhibited total sodium current increases after exposure to TNF-α, indicating that these effects were independent of SUMOylation of CRMP2. In conclusion, TNF-α sensitizes DRG neurons via augmentation of whole cell sodium current. This may underlie the pronociceptive effects of TNF-α and suggests a molecular mechanism responsible for pain hypersensitivity in diabetic neuropathy patients.

Identification of oxytocin receptor in the dorsal horn and nociceptive dorsal root ganglion neurons

Neuropeptides ◽  
2013 ◽  
Vol 47 (2) ◽  
pp. 117-123 ◽  
Author(s):  
Y. Moreno-López ◽  
G. Martínez-Lorenzana ◽  
M. Condés-Lara ◽  
G. Rojas-Piloni
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Horn ◽  
Dorsal Root ◽  
Oxytocin Receptor ◽  
Dorsal Root Ganglion Neurons ◽  
Ganglion Neurons

Kv1.1 Channels of Dorsal Root Ganglion Neurons Are Inhibited byn-Butyl-p-aminobenzoate, a Promising Anesthetic for the Treatment of Chronic Pain

2003 ◽  
Vol 304 (2) ◽  
pp. 531-538 ◽  
Author(s):  
J. P. Beekwilder ◽  
M. E. O'Leary ◽  
L. P. van den Broek ◽  
G. Th. H. Van Kempen ◽  
D. L. Ypey ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Dorsal Root Ganglion Neurons ◽  
Ganglion Neurons

scholarly journals L-bupivacaine Inhibition of Nociceptive Transmission in Rat Peripheral and Dorsal Horn Neurons

2020 ◽  
Vol 134 (1) ◽  
pp. 88-102
Author(s):  
Daisuke Uta ◽  
Kohei Koga ◽  
Hidemasa Furue ◽  
Keiji Imoto ◽  
Megumu Yoshimura
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Horn ◽  
Dorsal Root ◽  
Spinal Dorsal Horn ◽  
Dorsal Root Ganglion Neurons ◽  
Evoked Responses ◽  
Half Maximum ◽  
Sodium Currents ◽  
Spinal Dorsal ◽  
Ganglion Neurons

Background Although the widely used single L-enantiomers of local anesthetics have less toxic effects on the cardiovascular and central nervous systems, the mechanisms mediating their antinociceptive actions are not well understood. The authors hypothesized that significant differences in the ion channel blocking abilities of the enantiomers of bupivacaine would be identified. Methods The authors performed electrophysiologic analysis on rat dorsal root ganglion neurons in vitro and on spinal transmissions in vivo. Results In the dorsal root ganglion, these anesthetics decreased the amplitudes of action potentials. The half-maximum inhibitory concentrations of D-enantiomer D-bupivacaine were almost equal for Aβ (29.5 μM), Aδ (29.7μM), and C (29.8 μM) neurons. However, the half-maximum inhibitory concentrations of L-bupivacaine was lower for Aδ (19.35 μM) and C (19.5 μM) neurons than for A β (79.4 μM) neurons. Moreover, D-bupivacaine almost equally inhibited tetrodotoxin-resistant (mean ± SD: 15.8 ± 10.9% of the control, n = 14, P < 0.001) and tetrodotoxin-sensitive (15.4 ± 15.6% of the control, n = 11, P = 0.004) sodium currents. In contrast, L-bupivacaine suppressed tetrodotoxin-resistant sodium currents (26.1 ± 19.5% of the control, n = 18, P < 0.001) but not tetrodotoxin-sensitive sodium currents (74.5 ± 18.2% of the control, n = 11, P = 0.477). In the spinal dorsal horn, L-bupivacaine decreased the area of pinch-evoked excitatory postsynaptic currents (39.4 ± 11.3% of the control, n = 7, P < 0.001) but not touch-evoked responses (84.2 ± 14.5% of the control, n = 6, P = 0.826). In contrast, D-bupivacaine equally decreased pinch- and touch-evoked responses (38.8 ± 9.5% of the control, n = 6, P = 0.001, 42.9 ± 11.8% of the control, n = 6, P = 0.013, respectively). Conclusions These results suggest that the L-enantiomer of bupivacaine (L-bupivacaine) effectively inhibits noxious transmission to the spinal dorsal horn by blocking action potential conduction through C and Aδ afferent fibers. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

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