scholarly journals C/EBPβ Participates in Nerve Trauma-Induced TLR7 Upregulation in Primary Sensory Neurons

2021 ◽  
Author(s):  
Long He ◽  
Jing Cao ◽  
Bao-Chun Jiang ◽  
Jian-Jun Yang ◽  
Yuan-Xiang Tao ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Thermal Hyperalgesia ◽  
Spinal Nerve ◽  
Spontaneous Pain ◽  
Primary Sensory Neurons ◽  
Mechanical Stimuli ◽  
Level Increase ◽  
Enhancer Binding Protein ◽  
Nerve Trauma

Abstract Nerve trauma-induced toll-like receptor 7 (TLR7) expression level increase in primary sensory neurons in the damaged dorsal root ganglion (DRG) avails to neuropathic pain, but the reason is still unknown. In the current study, we showed that unilateral lumbar 4 (L4) spinal nerve ligation (SNL) upregulated CCAAT/enhancer-binding protein-β (C/EBPβ) expression in ipsilateral L4 DRG. Preventing this elevation attenuated the SNL-induced upregulation of TLR7 in the ipsilateral L4 DRG and inhibited cold/thermal hyperalgesia and mechanical allodynia. Mimicking nerve trauma-induced C/EBPβ upregulation generated an elevated level of TLR7 in injected DRG, augmented responses to cold/thermal/mechanical stimuli while causing ipsilateral spontaneous pain with no SNL. Mechanistically, SNL upregulated binding of increased C/EBPβ to Tlr7 promoter in ipsilateral L4 DRG. Accorded that C/EBPβ could trigger the activation of Tlr7 promoter and co-expressed with Tlr7 mRNA in individual DRG neurons, our findings strongly suggest the role of C/EBPβ in nerve trauma-mediated TLR7 upregulation in damaged primary sensory neurons.

Hypoglycemic detection at the portal vein is mediated by capsaicin-sensitive primary sensory neurons

2007 ◽  
Vol 293 (1) ◽  
pp. E96-E101 ◽  
Author(s):  
Satoshi Fujita ◽  
MaryAnn Bohland ◽  
Graciela Sanchez-Watts ◽  
Alan G. Watts ◽  
Casey M. Donovan
Keyword(s):  
Portal Vein ◽  
Sensory Neurons ◽  
Jugular Vein ◽  
Immunohistochemical Analysis ◽  
Nerve Fibers ◽  
Similar Response ◽  
Primary Sensory Neurons ◽  
Calcitonin Gene ◽  
Epinephrine Concentration

To elucidate the type of spinal afferent involved in hypoglycemic detection at the portal vein, we considered the potential role of capsaicin-sensitive primary sensory neurons. Specifically, we examined the effect of capsaicin-induced ablation of portal vein afferents on the sympathoadrenal response to hypoglycemia. Under anesthesia, the portal vein was isolated in rats and either capsaicin (CAP) or the vehicle (CON) solution applied topically. During the same surgery, the carotid artery (sampling) and jugular vein (infusion) were cannulated. One week later, all animals underwent a hyperinsulinemic hypoglycemic clamp, with glucose (variable) and insulin (25 mU·kg−1·min−1) infused via the jugular vein. Systemic hypoglycemia (2.76 ± 0.05 mM) was induced by minute 75 and sustained until minute 105. By design, no significant differences were observed in arterial glucose or insulin concentrations between groups. When hypoglycemia was induced in CON, the plasma epinephrine concentration increased from 0.67 ± 0.05 nM at basal to 36.15 ± 2.32 nM by minute 105. Compared with CON, CAP animals demonstrated an 80% suppression in epinephrine levels by minute 105, 7.11 ± 0.55 nM ( P < 0.001). A similar response to hypoglycemia was observed for norepinephrine, with CAP values suppressed by 48% compared with CON. Immunohistochemical analysis of the portal vein revealed an 85% decrease in the number of calcitonin gene-related peptide-reactive nerve fibers following capsaicin-induced ablation. That the suppression in the sympathoadrenal response was comparable to our previous findings for total denervation of the portal vein indicates that hypoglycemic detection at the portal vein is mediated by capsaicin-sensitive primary sensory neurons.

Involvement of Persistent Na+ Current in Spike Initiation in Primary Sensory Neurons of the Rat Mesencephalic Trigeminal Nucleus

2007 ◽  
Vol 97 (3) ◽  
pp. 2385-2393 ◽  
Author(s):  
Youngnam Kang ◽  
Mitsuru Saito ◽  
Hajime Sato ◽  
Hiroki Toyoda ◽  
Yoshinobu Maeda ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Pyramidal Neurons ◽  
Low Voltage ◽  
Primary Sensory Neurons ◽  
Trigeminal Nucleus ◽  
Mesencephalic Trigeminal Nucleus ◽  
Bath Application ◽  
Spike Initiation ◽  
Activation Delay

It was recently shown that the persistent Na+ current ( INaP) is generated in the proximal axon in response to somatic depolarization in neocortical pyramidal neurons, although the involvement of INaP in spike initiation is still unclear. Here we show a potential role of INaP in spike initiation of primary sensory neurons in the mesencephalic trigeminal nucleus (MTN) that display a backpropagation of the spike initiated in the stem axon toward the soma in response to soma depolarization. Riluzole (10 μM) and tetrodotoxin (TTX, 10 nM) caused an activation delay or a stepwise increase in the threshold for evoking soma spikes (S-spikes) without affecting the spike itself. Simultaneous patch-clamp recordings from the soma and axon hillock (AH) revealed that bath application of 50 nM TTX increased the delay in spike activation in response to soma depolarization, leaving the spike-backpropagation time from the AH to soma unchanged. This indicates that the increase in activation delay occurred in the stem axon. Furthermore, under a decreasing intracellular concentration gradient of QX-314 from the soma to AH created by QX-314–containing and QX-314–free patch pipettes, the amplitude and maximum rate of rise (MRR) of AH-spikes decreased with an increase in the activation delay following repetition of current-pulse injections, whereas S-spikes displayed decreases of considerably lesser degree in amplitude and MRR. This suggests that compared to S-spikes, AH-spikes more accurately reflect the attenuation of axonal spike by QX-314, consistent with the nature of spike backpropagation. These observations strongly suggest that low-voltage–activated INaP is involved in spike initiation in the stem axon of MTN neurons.

The Role of Protons in the Activation of Primary Sensory Neurons

1999 ◽  
pp. 33-42
Author(s):  
P. Geppetti ◽  
S. Amadesi ◽  
M. Tognetto ◽  
F. M. L. Ricciardolo
Keyword(s):  
Sensory Neurons ◽  
Primary Sensory Neurons

scholarly journals Cutaneous neurturin overexpression alters mechanical, thermal, and cold responsiveness in physiologically identified primary afferents

2017 ◽  
Vol 117 (3) ◽  
pp. 1258-1265 ◽  
Author(s):  
Michael P. Jankowski ◽  
Kyle M. Baumbauer ◽  
Ting Wang ◽  
Kathryn M. Albers ◽  
Brian M. Davis ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Neurotrophic Factors ◽  
Ex Vivo ◽  
Second Phase ◽  
Primary Sensory Neurons ◽  
Mechanical Stimuli ◽  
Wild Type Littermate ◽  
Basal Keratinocytes ◽  
C Fiber ◽  
The Impact

Neurotrophic factors play an important role in the regulation of functional properties of sensory neurons under normal and pathological conditions. The GDNF family member neurturin is one such factor that has been linked to modulating responsiveness to peripheral stimuli. Neurturin binds to the GFRα2 receptor, a receptor found primarily in isolectin B4-expressing polymodal cutaneous nociceptors. Previous work has shown that knockout of GFRα2 alters heat, but not mechanical, responses in dissociated sensory neurons and reduces pain-related behaviors during the second phase of the formalin test. Research has also shown that overexpression of neurturin in basal keratinocytes increases behavioral responsiveness to mechanical stimulation and innocuous cooling of the skin without affecting noxious heat responses. Here we directly examined the impact of neurturin overexpression on cutaneous afferent function. We compared physiological responses of individual sensory neurons to mechanical and thermal stimulation of the skin, using an ex vivo skin-nerve-dorsal root ganglion-spinal cord preparation produced from neurturin-overexpressing (NRTN/OE) mice and wild-type littermate controls. We found that neurturin overexpression increases responsiveness to innocuous mechanical stimuli in A-fiber nociceptors, alters thermal responses in the polymodal subpopulation of C-fiber sensory neurons, and changes the relative numbers of mechanically sensitive but thermally insensitive C-fiber afferents. These results demonstrate the potential roles of different functional groups of sensory neurons in the behavioral changes observed in mice overexpressing cutaneous neurturin and highlight the importance of neurturin in regulating cutaneous afferent response properties. NEW & NOTEWORTHY GDNF family neurotrophic factors regulate the development and function of primary sensory neurons. Of these, neurturin has been shown to modulate mechanical and cooling sensitivity behaviorally. Here we show that overexpression of neurturin in basal keratinocytes regulates mechanical responsiveness in A-fiber primary sensory neurons while increasing the overall numbers of cold-sensing units. Results demonstrate a crucial role for cutaneous neurturin in modulating responsiveness to peripheral stimuli at the level of the primary afferent.

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