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.

Pathophysiology of trigeminal neuralgia: new evidence from a trigeminal ganglion intraoperative microneurographic recording

2004 ◽  
Vol 101 (5) ◽  
pp. 872-873 ◽  
Author(s):  
Kim J. Burchiel ◽  
Thomas K. Baumann
Keyword(s):  
Trigeminal Neuralgia ◽  
Trigeminal Ganglion ◽  
Physiological Mechanism ◽  
Vascular Compression ◽  
Entry Zone ◽  
Content Type ◽  
Root Entry Zone ◽  
Trigeminal Ganglion Neurons ◽  
Ganglion Neurons ◽  
New Evidence

✓ The origin of trigeminal neuralgia (TN) appears to be vascular compression of the trigeminal nerve at the root entry zone; however, the physiological mechanism of this disorder remains uncertain. The authors obtained intraoperative microneurographic recordings from trigeminal ganglion neurons in a patient with TN immediately before percutaneous radiofrequency-induced gangliolysis. Their findings are consistent with the idea that the pain of TN is generated, at least in part, by an abnormal discharge within the peripheral nervous system.

scholarly journals Role of the Oestrogen Receptors GPR30 and ERα in Peripheral Sensitization: Relevance to Trigeminal Pain Disorders in Women

Cephalalgia ◽  
2009 ◽  
Vol 29 (7) ◽  
pp. 729-741 ◽  
Author(s):  
CS Liverman ◽  
JW Brown ◽  
R Sandhir ◽  
KE McCarson ◽  
NEJ Berman
Keyword(s):  
Trigeminal Ganglion ◽  
Oestrogen Receptor ◽  
Temporomandibular Disorder ◽  
Small Diameter ◽  
Peripheral Sensitization ◽  
Sprague Dawley ◽  
Oestrogen Receptor Alpha ◽  
Trigeminal Ganglion Neurons ◽  
Ganglion Neurons

Oestrogen increases facial allodynia through its actions on activation of the MAPK extracellular-signal regulated kinase (ERK) in trigeminal ganglion neurons. This goal of study was to determine which oestrogen receptor is required for behavioural sensitization. Immunohistochemical studies demonstrated the presence of oestrogen receptor alpha (ERα) in nuclei of larger neurons and cytoplasm of smaller neurons, and the novel oestrogen receptor G-protein coupled receptor 30 (GPR30) in small diameter neurons that also contained peripherin, a marker of unmyelinated C-fibres. Specific agonists for ERα (PPT) and GPR30 (G-1), but not ERβ (DPN), activated ERK in trigeminal ganglion neurons in vitro. Both G-1 and PPT treatment increased allodynia after CFA injections into the masseter of ovariectomized Sprague-Dawley rats. Treatment with oestrogen increased expression of ERα but not GPR30, while masseter inflammation increased GRP30 but not ER α. Differential modulation of these ERK-coupled receptors by oestrogen and inflammation may play a role in painful episodes of temporomandibular disorder and migraine.

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.

scholarly journals Dexmedetomidine Inhibits Voltage-Gated Sodium Channels via α2-Adrenoceptors in Trigeminal Ganglion Neurons

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Sang-Taek Im ◽  
Youn Yi Jo ◽  
Gayoung Han ◽  
Hyun Jung Jo ◽  
Yong Ho Kim ◽  
...  
Keyword(s):  
G Protein ◽  
Sodium Channels ◽  
Trigeminal Ganglion ◽  
Trigeminal System ◽  
Voltage Gated ◽  
Analgesic Effects ◽  
Voltage Gated Sodium Channels ◽  
New Findings ◽  
Orofacial Region ◽  
Ganglion Neurons

Dexmedetomidine, an α2-adrenoceptor agonist, is widely used as a sedative and analgesic agent in a number of clinical applications. However, little is known about the mechanism by which it exerts its analgesic effects on the trigeminal system. Two types of voltage-gated sodium channels, Nav1.7 and Nav1.8, as well as α2-adrenoceptors are expressed in primary sensory neurons of the trigeminal ganglion (TG). Using whole-cell patch-clamp recordings, we investigated the effects of dexmedetomidine on voltage-gated sodium channel currents (INa) via α2-adrenoceptors in dissociated, small-sized TG neurons. Dexmedetomidine caused a concentration-dependent inhibition of INa in small-sized TG neurons. INa inhibition by dexmedetomidine was blocked by yohimbine, a competitive α2-adrenoceptor antagonist. Dexmedetomidine-induced inhibition of INa was mediated by G protein-coupled receptors (GPCRs) as this effect was blocked by intracellular perfusion with the G protein inhibitor GDPβ-S. Our results suggest that the INa inhibition in small-sized TG neurons, mediated by the activation of Gi/o protein-coupled α2-adrenoceptors, might contribute to the analgesic effects of dexmedetomidine in the trigeminal system. Therefore, these new findings highlight a potential novel target for analgesic drugs in the orofacial region.

Neurotrophin-4 is a target-derived neurotrophic factor for neurons of the trigeminal ganglion

Development ◽  
1993 ◽  
Vol 117 (4) ◽  
pp. 1345-1353 ◽  
Author(s):  
C.F. Ibanez ◽  
P. Ernfors ◽  
T. Timmusk ◽  
N.Y. Ip ◽  
E. Arenas ◽  
...  
Keyword(s):  
Trigeminal Ganglion ◽  
Neurotrophic Factor ◽  
Cellular Localization ◽  
Trigeminal Ganglia ◽  
Bdnf Mrna ◽  
Naturally Occurring ◽  
Whisker Pad ◽  
Trigeminal Ganglion Neurons ◽  
Ganglion Neurons

The cellular localization of mRNA for neurotrophin-4 (NT-4), a novel neurotrophic factor, in the developing whisker follicles and skin of the embryonic rat is demonstrated by in situ hybridization. Levels of NT-4 mRNA in the whisker pad decrease between embryonic day 13 (E13) and E20, correlating in time with the onset of naturally occurring neuronal death in the innervating trigeminal ganglion. In addition to NT-4, brain-derived neuotrophic factor (BDNF) mRNA is also shown to be expressed in the rat embryonic whisker follicles although in a different cellular localization, which combined with previous data on the expression of NGF and NT-3 mRNAs, shows that all four neurotrophins are expressed during development of this structure. NT-4 protein is shown to elicit neurite outgrowth from explanted embryonic trigeminal ganglia and to promote neuronal survival of dissociated trigeminal ganglion neurons when cultured during the phase of cell death. NT-4 and NT-3 mainly support different neuronal subpopulations, whereas some NT-4-responsive cells appear to respond also to NGF and BDNF. Analysis of mRNAs for members of the Trk family of neurotrophin receptors in neurons rescued by different neurotrophins demonstrates the presence of distinct neuronal subpopulations that respond to specific combinations of these factors. Based on these results we propose that NT-4, together with the other three neurotrophins, orchestrate the innervation of the different structures of the developing whisker pad by the trigeminal ganglion, acting as target-derived neurotrophic factors for different subpopulations of trigeminal ganglion neurons.

Transmission electron microscopic study of large myelinated fiber injury from percutaneous trigeminal ganglion compression for trigeminal neuralgia in a rabbit model

1991 ◽  
Vol 49 ◽  
pp. 88-89
Author(s):  
B.F. Hoeflinger ◽  
W.T. Gunning ◽  
J.A. Brown ◽  
A. Eckhardt ◽  
M. McDaniel ◽  
...  
Keyword(s):  
Trigeminal Neuralgia ◽  
Trigeminal Ganglion ◽  
Rabbit Model ◽  
Nerve Fibers ◽  
Trigeminal System ◽  
Myelinated Fiber ◽  
Electron Microscopic ◽  
Axon Terminals ◽  
C Fibers ◽  
Ganglion Neurons

Trigeminal neuralgia (TN) is a disorder characterized by paroxysmal, lancing facial pain confined to the distribution of trigeminal nerve fibers. A procedure to relieve this sensation, Percutaneous Trigeminal Ganglion Compression(PTGC), was introduced in 1983 and has been shown in clinical studies to be an effective treatment for TN. The effect of PTGC on the trigeminal system has not been adequately studied. In a previous study. New Zealand White rabbits were utilized in an attempt to evaluate the consequences of PTGC at the light microscopic level. This investigation revealed a differential demyelination and fragmentation of axons in the trigeminal(V) sensory root while trigeminal ganglion neurons were found to be preserved. Immunocytochemical stains of the spinal trigeminal tract showed no specific loss of fine caliber Ad and C-fibers. Degeneration of axon terminals was found in the deeper layers of the spinal trigeminal nucleus, the region corresponding to the termination of large myelinated axons suggesting a differential loss of these specific fibers.

scholarly journals Oxytocin-Dependent Regulation of TRPs Expression in Trigeminal Ganglion Neurons Attenuates Orofacial Neuropathic Pain following Infraorbital Nerve Injury in Rats

2020 ◽  
Vol 21 (23) ◽  
pp. 9173
Author(s):  
Masatoshi Ando ◽  
Yoshinori Hayashi ◽  
Suzuro Hitomi ◽  
Ikuko Shibuta ◽  
Akihiko Furukawa ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Trigeminal Ganglion ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Infraorbital Nerve ◽  
Transient Receptor Potential Vanilloid ◽  
Withdrawal Threshold ◽  
Whisker Pad ◽  
Ganglion Neurons

We evaluated the mechanisms underlying the oxytocin (OXT)-induced analgesic effect on orofacial neuropathic pain following infraorbital nerve injury (IONI). IONI was established through tight ligation of one-third of the infraorbital nerve thickness. Subsequently, the head withdrawal threshold for mechanical stimulation (MHWT) of the whisker pad skin was measured using a von Frey filament. Trigeminal ganglion (TG) neurons innervating the whisker pad skin were identified using a retrograde labeling technique. OXT receptor-immunoreactive (IR), transient receptor potential vanilloid 1 (TRPV1)-IR, and TRPV4-IR TG neurons innervating the whisker pad skin were examined on post-IONI day 5. The MHWT remarkably decreased from post-IONI day 1 onward. OXT application to the nerve-injured site attenuated the decrease in MHWT from day 5 onward. TRPV1 or TRPV4 antagonism significantly suppressed the decrement of MHWT following IONI. OXT receptors were expressed in the uninjured and Fluoro-Gold (FG)-labeled TG neurons. Furthermore, there was an increase in the number of FG-labeled TRPV1-IR and TRPV4-IR TG neurons, which was inhibited by administering OXT. This inhibition was suppressed by co-administration with an OXT receptor antagonist. These findings suggest that OXT application inhibits the increase in TRPV1-IR and TRPV4-IR TG neurons innervating the whisker pad skin, which attenuates post-IONI orofacial mechanical allodynia.

Liver Toxicity in Rats Fed A Mixture of Pcb Congeners and 2,3,7,8-Tcdd

1997 ◽  
Vol 3 (S2) ◽  
pp. 51-52
Author(s):  
B.J. Cornell ◽  
A. Singh ◽  
I. Chu
Keyword(s):  
Aromatic Compounds ◽  
Liver Toxicity ◽  
Corn Oil ◽  
Morphological Changes ◽  
Test Substance ◽  
Sprague Dawley ◽  
Morphological Alterations ◽  
Pcb Congeners ◽  
Transmission Electron ◽  
Sprague Dawley Rats

Polyhalogenated aromatic compounds such as polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins (PCDDs) continue to be environmental contaminants because of their bioaccumulation in the food chain and high resistance to biodegradation. The current study was undertaken to determine if a mixture of PCB congeners (WHO-IPCS) were interactive with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in producing morphological changes in the rat liver. Both compounds are known to produce a broad range of biochemical and morphological alterations including enzyme induction.Groups (N=5) of female Sprague-Dawley rats were administered TCDD (0, 2.5, 25, 250, 1000 ng/kg bw/day) or PCB (0, 2, 20 μg/kg bw/day) alone, or in combination with each concentration of both compounds. Incorrect concentrations were published in a previous abstract. The test substance was mixed with corn oil and given by gavage at 2 ml/kg daily for 28 days. At the end of the experiment, the rats were killed and liver samples were prepared for transmission electron microscopy.

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