scholarly journals The Role of Prostaglandin E1 as a Pain Mediator through Facilitation of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 2 via the EP2 Receptor in Trigeminal Ganglion Neurons of Mice

2021 ◽  
Vol 22 (24) ◽  
pp. 13534
Author(s):  
Jean Kwon ◽  
Young In Choi ◽  
Hang Joon Jo ◽  
Sang Hoon Lee ◽  
Han Kyu Lee ◽  
...  
Keyword(s):  
Trigeminal Ganglion ◽  
Mechanical Allodynia ◽  
Intradermal Injection ◽  
Hcn Channel ◽  
Nociceptive Neurons ◽  
Inflammatory Conditions ◽  
Gated Channel ◽  
Ganglion Neurons ◽  
Ep2 Receptor

Cyclooxygenase metabolizes dihomo-γ-linolenic acid and arachidonic acid to form prostaglandin (PG) E, including PGE1 and PGE2, respectively. Although PGE2 is well known to play an important role in the development and maintenance of hyperalgesia and allodynia, the role of PGE1 in pain is unknown. We confirm whether PGE1 induced pain using orofacial pain behavioral test in mice and determine the target molecule of PGE1 in TG neurons with whole-cell patch-clamp and immunohistochemistry. Intradermal injection of PGE1 to the whisker pads of mice induced a reduced threshold, enhancing the excitability of HCN channel-expressing trigeminal ganglion (TG) neurons. The HCN channel-generated inward current (Ih) was increased by 135.3 ± 4.8% at 100 nM of PGE1 in small- or medium-sized TG, and the action of PGE1 on Ih showed a concentration-dependent effect, with a median effective dose (ED50) of 29.3 nM. Adenylyl cyclase inhibitor (MDL12330A), 8-bromo-cAMP, and the EP2 receptor antagonist AH6809 inhibited PGE1-induced Ih. Additionally, PGE1-induced mechanical allodynia was blocked by CsCl and AH6809. PGE1 plays a role in mechanical allodynia through HCN2 channel facilitation via the EP2 receptor in nociceptive neurons, suggesting a potential therapeutic target in that PGE1 could be involved in pain as endogenous substances under inflammatory conditions.

Central sensitization following intradermal injection of capsaicin

1997 ◽  
Vol 20 (3) ◽  
pp. 471-471 ◽  
Author(s):  
William D. Willis
Keyword(s):  
Amino Acids ◽  
Substance P ◽  
Central Sensitization ◽  
Mechanical Allodynia ◽  
Excitatory Amino Acids ◽  
Intradermal Injection ◽  
Mechanical Hyperalgesia ◽  
Spinothalamic Tract ◽  
Nociceptive Neurons ◽  
Primary Hyperalgesia

Intradermal capsaicin in humans causes pain, primary hyperalgesia, and secondary mechanical hyperalgesia and allodynia. Parallel changes occur in the responses of primate spinothalamic tract cells and in rat behavior. Neurotransmitters that trigger secondary mechanical hyperalgesia and allodynia include excitatory amino acids and substance P. Secondary mechanical allodynia is actively maintained by central mechanisms. Our group has investigated mechanisms of central sensitization of nociceptive neurons by examining the responses to intradermal injection of capsaicin. These experiments are pertinent to issues raised by coderre & katz (sect. 2).

scholarly journals Application of Purified Botulinum Type A Neurotoxin to Treat Experimental Trigeminal Neuropathy in Rats and Patients with Urinary Incontinence and Prostatic Hyperplasia

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Yoshizo Matsuka ◽  
Teruhiko Yokoyama ◽  
Yumiko Yamamoto ◽  
Tomonori Suzuki ◽  
Ni Nengah Dwi Fatmawati ◽  
...  
Keyword(s):  
Urinary Incontinence ◽  
Trigeminal Ganglion ◽  
Simple Procedure ◽  
Type A ◽  
Intradermal Injection ◽  
Prostatic Hyperplasia ◽  
Infraorbital Nerve ◽  
Trigeminal Neuropathy ◽  
Trigeminal Ganglion Neurons ◽  
Ganglion Neurons

Type A neurotoxin (NTX) ofClostridium botulinumwas purified by a simple procedure using a lactose gel column. The toxicity of this purified toxin preparation was retained for at least 1 year at −30°C by supplementation with either 0.1% albumin or 0.05% albumin plus 1% trehalose. When purified NTX was used to treat 49 patients with urinary incontinence caused by either refractory idiopathic or neurogenic detrusor overactivity, 36 patients showed significant improvement in symptoms. These beneficial effects were also observed in cases of prostatic hyperplasia. The results obtained with NTX were similar to that of Botox. The effects of NTX on trigeminal neuralgia induced by infraorbital nerve constriction (IoNC) in rats were also studied. Trigeminal ganglion neurons from ipsilateral to IoNC exhibited significantly faster onset of FM4-64 release than sham-operated contralateral neurons. Intradermal injection of NTX in the area of IoNC alleviated IoNC-induced pain behavior and reduced the exaggerated FM4-64 release in trigeminal ganglion neurons.

scholarly journals CXCL12/CXCR4 signaling induced itch and pain sensation in a murine model of allergic contact dermatitis

2020 ◽  
Vol 16 ◽  
pp. 174480692092642
Author(s):  
Wenliang Su ◽  
Jiawen Yu ◽  
Qing Liu ◽  
Lulu Ma ◽  
Yuguang Huang
Keyword(s):  
Contact Dermatitis ◽  
Allergic Contact Dermatitis ◽  
Trigeminal Ganglion ◽  
Small Diameter ◽  
Intradermal Injection ◽  
Pain Sensation ◽  
Cxcr4 Antagonist ◽  
Cxcr4 Signaling ◽  
Ganglion Neurons ◽  
Allergic Contact

Allergic contact dermatitis is a skin inflammatory disease manifested with itch and pain symptom around the inflamed area. Chemokines such as CXCL12 are involved in the pathophysiology of allergic contact dermatitis, but little has been known about the effect of CXCL12/CXCR4 signaling for nociceptive sensation accompanying allergic contact dermatitis. Our study showed that CXCL12 and CXCR4 were upregulated in trigeminal ganglion with the progression of allergic contact dermatitis through western blotting and immunofluorescence. CXCL12 and CXCR4 were mainly upregulated in small-diameter neurons, which were co-localized with nociceptive markers in trigeminal ganglion. CXCR4 and CXCL12 were also expressed in trigeminal ganglion neurons retrograded from the skin lesion. Intradermal injection of CXCL12 enhanced the itch- and pain-like behavior which could be relieved by AMD3100, a CXCR4 antagonist, without changes of mast cells. Our findings suggested that blockade of CXCL12/CXCR4 signaling pathway might be beneficial to relieve itch and pain sensation accompanying allergic contact dermatitis.

scholarly journals P2X3 receptor upregulation in trigeminal ganglion neurons through TNFα production in macrophages contributes to trigeminal neuropathic pain in rats

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Momoko Koizumi ◽  
Sayaka Asano ◽  
Akihiko Furukawa ◽  
Yoshinori Hayashi ◽  
Suzuro Hitomi ◽  
...  
Keyword(s):  
Trigeminal Neuralgia ◽  
Trigeminal Ganglion ◽  
Mechanical Allodynia ◽  
Morphological Changes ◽  
Activated Macrophages ◽  
Sprague Dawley ◽  
Necrosis Factor Alpha ◽  
Orofacial Region ◽  
Whisker Pad ◽  
Ganglion Neurons

Abstract Background Trigeminal neuralgia is a characteristic disease that manifests as orofacial phasic or continuous severe pain triggered by innocuous orofacial stimulation; its mechanisms are not fully understood. In this study, we established a new animal model of trigeminal neuralgia and investigated the role of P2X3 receptor (P2X3R) alteration in the trigeminal ganglion (TG) via tumor necrosis factor alpha (TNFα) signaling in persistent orofacial pain. Methods Trigeminal nerve root compression (TNC) was performed in male Sprague-Dawley rats. Changes in the mechanical sensitivity of whisker pad skin, amount of TNFα in the TG, and number of P2X3R and TNF receptor-2 (TNFR2)-positive TG neurons were assessed following TNC. The effects of TNFR2 antagonism in TG and subcutaneous P2X3R antagonism on mechanical hypersensitivity following TNC were examined. Results TNC induced unilateral continuous orofacial mechanical allodynia, which was depressed by carbamazepine. The accumulation of macrophages showing amoeboid-like morphological changes and expression of TNFα in the TG was remarkably increased following TNC treatment. The number of P2X3R- and TNFR2-positive TG neurons innervating the orofacial skin was significantly increased following TNC. TNFα was released from activated macrophages that occurred in the TG following TNC, and TNFR2 antagonism in the TG significantly diminished the TNC-induced increase in P2X3R-immunoreactive TG neurons. Moreover, subcutaneous P2X3R antagonism in the whisker pad skin significantly depressed TNC-induced mechanical allodynia. Conclusions Therefore, it can be concluded that the signaling of TNFα released from activated macrophages in the TG induces the upregulation of P2X3R expression in TG neurons innervating the orofacial region, resulting in orofacial mechanical allodynia following TNC.

Requirement of neurotrophin-3 for the survival of proliferating trigeminal ganglion progenitor cells

Development ◽  
1996 ◽  
Vol 122 (8) ◽  
pp. 2405-2414 ◽  
Author(s):  
W.M. elshamy ◽  
P. Ernfors
Keyword(s):  
Cell Death ◽  
Progenitor Cells ◽  
Trigeminal Ganglion ◽  
Physiological Role ◽  
Proliferating Cells ◽  
Neurotrophin 3 ◽  
Dividing Cells ◽  
Incorporated Brdu ◽  
Ganglion Neurons

The aim of this study was to identify the physiological role of neurotrophin-3 (NT-3) in the development of trigeminal ganglion sensory neurons. For this purpose we have analysed mice carrying a deletion in the NT-3 gene (NT-3−/− mice). In these mice, by embryonic day (E) 11.25% of the trigeminal ganglion neurons were absent and one day later, approximately 50% were absent, after which no further significant changes were observed. Mice carrying one functional NT-3 gene (NT-3+/− mice) displayed a less severe deficit than that of NT-3−/− mice. Whereas programmed cell death occurred between E12 and E14 in the control mice, pronounced excessive cell death was apparent prior to this in the NT-3−/− mice. The excessive cell death led to a progressive decline in the number of proliferating cells without a significant change in the fraction of dividing cells and total number of neurons, indicating that the neuronal deficit of NT-3−/− mice was caused by cell death of trigeminal ganglion progenitors. Furthermore, the degenerating cells had incorporated BrdU, a nucleotide analogue which labels proliferating cells, and expressed nestin, a marker for progenitor cells. Only rarely were degenerating cells seen to express peripherin, present in postmitotic neurons. These data provide evidence that NT-3 is a survival factor for trigeminal ganglion progenitor cells, and suggests that limiting amounts of NT-3 could influence progenitor cell numbers during gangliogenesis.

scholarly journals Whisking in Air: Encoding of Kinematics by Trigeminal Ganglion Neurons in Awake Rats

2009 ◽  
Vol 101 (4) ◽  
pp. 1836-1846 ◽  
Author(s):  
V. Khatri ◽  
R. Bermejo ◽  
J. C. Brumberg ◽  
A. Keller ◽  
H. P. Zeigler
Keyword(s):  
Trigeminal Ganglion ◽  
High Reliability ◽  
Kinematic Parameter ◽  
Movement Direction ◽  
Trigeminal Ganglion Neurons ◽  
Ganglion Neurons ◽  
The Brain ◽  
Precise Time ◽  
Do So

Active sensing requires the brain to distinguish signals produced by external inputs from those generated by the animal's own movements. Because the rodent whisker musculature lacks proprioceptors, we asked whether trigeminal ganglion neurons encode the kinematics of the rat's own whisker movements in air. By examining the role of kinematics, we have extended previous findings showing that many neurons that respond during such movements do not do so consistently. Nevertheless, the majority (∼70%) of trigeminal ganglion neurons display significant correlations between firing rate and a kinematic parameter, and a subset, ∼30%, represent kinematics with high reliability. Preferential firing to movement direction was observed but was strongly modulated by movement amplitude and speed. However, in contrast to the precise time-locking that occurs in response to active whisker contacts, whisker movements in air generate temporally dispersed responses that are not time-locked to the onset of either protractions or retractions.

scholarly journals Sumatriptan activates TRPA1

2019 ◽  
Vol 2 ◽  
pp. 251581631984715
Author(s):  
Alexandru Babes ◽  
Cristian Neacsu ◽  
Michael JM Fischer ◽  
Karl Messlinger
Keyword(s):  
Side Effects ◽  
Trigeminal Ganglion ◽  
Transient Receptor Potential ◽  
Animal Experiments ◽  
Receptor Potential ◽  
Membrane Currents ◽  
Nociceptive Neurons ◽  
Trigeminal Ganglion Neurons ◽  
Transient Receptor ◽  
Ganglion Neurons

Background: Migraine therapy with sumatriptan may cause adverse side effects like pain at the injection site, muscle pain, and transient aggravation of headaches. In animal experiments, sumatriptan excited or sensitized slowly conducting meningeal afferents. We hypothesized that sumatriptan may activate transduction channels of the “irritant receptor,” the transient receptor potential ankyrin type (TRPA1) expressed in nociceptive neurons. Methods: Calcium microfluorometry was performed in HEK293t cells transfected with human TRPA1 (hTRPA1) or a mutated channel (TRPA1-3C) and in dissociated trigeminal ganglion neurons. Membrane currents were recorded in the whole-cell patch clamp configuration. Results: Sumatriptan (10 and 400 µM) evoked calcium transients in hTRPA1-expressing HEK293t cells also activated by the TRPA1 agonist carvacrol (100 µM). In TRPA1-3C-expressing HEK293t cells, sumatriptan had hardly any effect. In rat trigeminal ganglion neurons, sumatriptan, carvacrol, and the transient receptor potential vanillod type 1 agonist capsaicin (1 µM) generated robust calcium signals. All sumatriptan-sensitive neurons (8% of the sample) were also activated by carvacrol (14%) and capsaicin (48%). In HEK293-hTRPA1 cells, sumatriptan (100 µM) evoked outwardly rectifying currents, which were almost completely inhibited by the TRPA1 antagonist HC-030031 (10 µM). Conclusion: Sumatriptan activates TRPA1 channels inducing calcium inflow and membrane currents. TRPA1-dependent activation of primary afferents may explain the painful side effects of sumatriptan.

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