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International Journal of Molecular... Aug 2023Orofacial pain represents a multidisciplinary biomedical challenge involving basic and clinical research for which no satisfactory solution has been found. In this... (Review)
Review
Orofacial pain represents a multidisciplinary biomedical challenge involving basic and clinical research for which no satisfactory solution has been found. In this regard, trigeminal pain is described as one of the worst pains perceived, leaving the patient with no hope for the future. The aim of this review is to evaluate the latest discoveries on the involvement of neurotrophins in orofacial nociception, describing their role and expression in peripheral tissues, trigeminal ganglion, and trigeminal nucleus considering their double nature as "supporters" of the nervous system and as "promoters" of nociceptive transmission. In order to scan recent literature (last ten years), three independent researchers referred to databases PubMed, Embase, Google Scholar, Scopus, and Web of Science to find original research articles and clinical trials. The researchers selected 33 papers: 29 original research articles and 4 clinical trials. The results obtained by the screening of the selected articles show an interesting trend, in which the precise modulation of neurotrophin signaling could switch neurotrophins from being a "promoter" of pain to their beneficial neurotrophic role of supporting the nerves in their recovery, especially when a structural alteration is present, as in neuropathic pain. In conclusion, neurotrophins could be interesting targets for orofacial pain modulation but more studies are necessary to clarify their role for future application in clinical practice.
Topics: Humans; Nerve Growth Factors; Facial Pain; Trigeminal Ganglion; Neuralgia; Signal Transduction
PubMed: 37569811
DOI: 10.3390/ijms241512438 -
ACS Chemical Neuroscience Jan 2011The capacity of cutaneous, including trigeminal endings, to detect chemicals is known as chemesthesis or cutaneous chemosensation. This sensory function involves the... (Review)
Review
The capacity of cutaneous, including trigeminal endings, to detect chemicals is known as chemesthesis or cutaneous chemosensation. This sensory function involves the activation of nociceptor and thermoreceptor endings and has a protective or defensive function, as many of these substances are irritants or poisonous. However, humans have also developed a liking for the distinct sharpness or pungency of many foods, beverages, and spices following activation of the same sensory afferents. Our understanding of the cellular and molecular mechanisms of chemosensation in the trigeminal system has experienced enormous progress in the past decade, following the cloning and functional characterization of several ion channels activated by physical and chemical stimuli. This brief review attempts to summarize our current knowledge in this field, including a functional description of various sensory channels, especially TRP channels, involved in trigeminal chemosensitivy. Finally, some of these new findings are discussed in the context of the pathophysiology of trigeminal chemosensation, including pain, pruritus, migraine, cough, airway inflammation, and ophthalmic diseases.
Topics: Animals; Chemoreceptor Cells; Humans; Pain; TRPV Cation Channels; Taste; Touch; Trigeminal Ganglion; Trigeminal Nerve
PubMed: 22778855
DOI: 10.1021/cn100102c -
Cellular and Molecular Neurobiology Feb 2024Calcitonin gene-related peptide (CGRP) is synthesized and secreted by trigeminal ganglion neurons, and is a key neuropeptide involved in pain and immune regulation. This...
Calcitonin gene-related peptide (CGRP) is synthesized and secreted by trigeminal ganglion neurons, and is a key neuropeptide involved in pain and immune regulation. This study investigates the expression of CGRP in the trigeminal ganglion (TG) and its regulatory role in the polarization of macrophages in rats with temporomandibular arthritis. A rat model of temporomandibular arthritis was established using CFA. Pain behavior was then observed. Temporomandibular joint (TMJ) and the TG were collected, and immunohistochemistry, immunofluorescence (IF) staining, and RT-qPCR were used to examine the expression of CGRP and macrophage-related factors. To investigate the impact of CGRP on macrophage polarization, both CGRP and its antagonist, CGRP 8-37, were separately administered directly within the TG. Statistical analysis revealed that within 24 h of inducing temporomandibular arthritis using CFA, there was a significant surge in CD86 positive macrophages within the ganglion. These macrophages peaked on the 7th day before beginning their decline. In this context, it's noteworthy that administering CGRP to the trigeminal ganglion can prompt these macrophages to adopt the M2 phenotype. Intriguingly, this study demonstrates that injecting the CGRP receptor antagonist (CGRP 8-37) to the ganglion counteracts this shift towards the M2 phenotype. Supporting these in vivo observations, we found that in vitro, CGRP indeed fosters the M2-type polarization of macrophages. CGRP can facilitate the conversion of macrophages into the M2 phenotype. The phenotypic alterations of macrophages within the TG could be instrumental in initiating and further driving the progression of TMJ disorders.
Topics: Animals; Rats; Calcitonin Gene-Related Peptide; Macrophages; Pain; Temporomandibular Joint Disorders; Trigeminal Ganglion
PubMed: 38363424
DOI: 10.1007/s10571-024-01456-7 -
Experimental Eye Research Jul 2022The normal cornea has no blood vessels but has abundant innervation. There is emerging evidence that sensory nerves, originated from the trigeminal ganglion (TG)...
The normal cornea has no blood vessels but has abundant innervation. There is emerging evidence that sensory nerves, originated from the trigeminal ganglion (TG) neurons, play a key role in corneal angiogenesis. In the current study, we examined the role of TG sensory neuron-derived calcitonin gene-related peptide (CGRP) in promoting corneal neovascularization (CNV). We found that CGRP was expressed in the TG and cultured TG neurons. In the cornea, minimal CGRP mRNA was detected and CGRP immunohistochemical staining was exclusively co-localized with corneal nerves, suggesting corneal nerves are likely the source of CGRP in the cornea. In response to intrastromal suture placement and neovascularization in the cornea, CGRP expression was increased in the TG. In addition, we showed that CGRP was potently pro-angiogenic, leading to vascular endothelial cell (VEC) proliferation, migration, and tube formation in vitro and corneal hemangiogenesis and lymphangiogenesis in vivo. In a co-culture system of TG neurons and VEC, blocking CGRP signaling in the conditioned media of TG neurons led to decreased VEC migration and tube formation. More importantly, subconjunctival injection of a CGRP antagonist CGRP8-37 reduced suture-induced corneal hemangiogenesis and lymphangiogenesis in vivo. Taken together, our data suggest that TG sensory neuron and corneal nerve-derived CGRP promotes corneal angiogenesis.
Topics: Calcitonin Gene-Related Peptide; Cornea; Corneal Neovascularization; Humans; Sensory Receptor Cells; Trigeminal Ganglion
PubMed: 35618042
DOI: 10.1016/j.exer.2022.109125 -
Anatomical Record (Hoboken, N.J. : 2007) Dec 2020Microvascular compression on the trigeminal root entry zone (TREZ) is the main etiology of trigeminal neuralgia (TN) patients. To investigate brain-derived neurotrophic...
Brain-derived neurotrophic factor and Glial cell line-derived neurotrophic factor expressions in the trigeminal root entry zone and trigeminal ganglion neurons of a trigeminal neuralgia rat model.
Microvascular compression on the trigeminal root entry zone (TREZ) is the main etiology of trigeminal neuralgia (TN) patients. To investigate brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) in the trigeminal ganglion (TG) and TREZ, immunofluorescence staining and Western blot were used in a rat TN model. Both BDNF and GDNF were observed in the TG neurons and TREZ. The expression of the BDNF dimer in the TG was increased in the TN group, while GDNF expression was decreased after compression injury. The BDNF dimer/pro-BDNF ratio in the TREZ of the TN group was higher than that in the sham group, but the GDNF expression in the TREZ was significantly lower than that in the sham group. These results suggested that compression injury in the TREZ of rats induced dynamic changes in BDNF and GDNF in both the TG and TREZ, and these changes are involved in the nociceptive transmission of the TN animal model.
Topics: Animals; Brain-Derived Neurotrophic Factor; Disease Models, Animal; Glial Cell Line-Derived Neurotrophic Factor; Male; Neurons; Rats; Rats, Sprague-Dawley; Trigeminal Ganglion; Trigeminal Nerve; Trigeminal Neuralgia
PubMed: 31922368
DOI: 10.1002/ar.24364 -
Pain Research & Management 2021Postherpetic neuralgia (PHN) is a painful, long-lasting condition as a consequence of nerve damage resulting from a herpes zoster infection. Although there are many...
Postherpetic neuralgia (PHN) is a painful, long-lasting condition as a consequence of nerve damage resulting from a herpes zoster infection. Although there are many different treatments available to reduce pain duration and severity, PHN is often refractory to them and no single therapy shows an effective cure for all cases of PHN, especially for those involving the ophthalmic branch of the trigeminal nerve. Pulsed radiofrequency (PRF) is a minimally invasive procedure for pain treatment that has been practiced over the past decade. However, its clinical efficacy and safety for treating PHN involving the ophthalmic branch of the trigeminal nerve have not been evaluated. . This study aimed to evaluate the efficacy and safety of PRF for treating PHN involving the ophthalmic branch of the trigeminal ganglion. . An observational study. . All patients received PRF of the ophthalmic branch of the trigeminal nerve, pain intensity was assessed by a visual analogue scale (VAS), and complications before and after PRF stimulation were noted. . Thirty-two patients with PHN of the ophthalmic branch were treated by PRF of the ophthalmic branch with controlled temperature at 42°C for 8 min. Pain relief, corneal reflex, sleep quality, and satisfaction were assessed for all patients. . Thirty out of 32 patients (93.75%) reported significant pain reduction after PRF treatment. Twenty-eight of them (87.5%) were satisfied with their sleep and obtained a pain score lower than 3 following the procedure. Only two patients had a recurrence of the severe burning pain and returned to the hospital for other medical therapies 2 weeks after the PRF procedure. No patient lost the corneal reflex. . This study is an observational study and a nonprospective trial with a short-term follow-up period. . PRF of the trigeminal ganglion of the ophthalmic branch can significantly reduce pain sensation and improve sleep quality and satisfaction for PHN of the ophthalmic branch.
Topics: Aged; Aged, 80 and over; Chronic Pain; Female; Herpes Zoster; Humans; Male; Middle Aged; Neuralgia, Postherpetic; Pain Management; Pulsed Radiofrequency Treatment; Trigeminal Ganglion; Trigeminal Neuralgia
PubMed: 34122683
DOI: 10.1155/2021/6638392 -
The Journal of Headache and Pain Apr 2021Butterbur root extract with its active ingredients petasin and isopetasin has been used in the prophylactic treatment of migraine for years, while its sites of action...
BACKGROUND
Butterbur root extract with its active ingredients petasin and isopetasin has been used in the prophylactic treatment of migraine for years, while its sites of action are not completely clear. Calcitonin gene-related peptide (CGRP) is known as a biomarker and promoting factor of migraine. We set out to investigate the impact of petasins on the CGRP release from trigeminal afferents induced by activation of the calcium conducting transient receptor potential channels (TRPs) of the subtypes TRPA1 and TRPV1.
METHODS
We used well-established in vitro preparations, the hemisected rodent skull and dissected trigeminal ganglia, to examine the CGRP release from rat and mouse cranial dura mater and trigeminal ganglion neurons, respectively, after pre-incubation with petasin and isopetasin. Mustard oil and capsaicin were used to stimulate TRPA1 and TRPV1 receptor channels. CGRP concentrations were measured with a CGRP enzyme immunoassay.
RESULTS
Pre-incubation with either petasin or isopetasin reduced mustard oil- and capsaicin-evoked CGRP release compared to vehicle in an approximately dose-dependent manner. These results were validated by additional experiments with mice expressing functionally deleted TRPA1 or TRPV1 receptor channels.
CONCLUSIONS
Earlier findings of TRPA1 receptor channels being involved in the site of action of petasin and isopetasin are confirmed. Furthermore, we suggest an important inhibitory effect on TRPV1 receptor channels and assume a cooperative action between the two TRP receptors. These mechanisms may contribute to the migraine prophylactic effect of petasins.
Topics: Animals; Calcitonin; Calcitonin Gene-Related Peptide; Mice; Rats; Sesquiterpenes; TRPA1 Cation Channel; TRPV Cation Channels; Trigeminal Ganglion
PubMed: 33849430
DOI: 10.1186/s10194-021-01235-5 -
Pain Physician Jul 2021Percutaneous radiofrequency ablation (RFA) of the trigeminal Gasserian ganglion via the foramen ovale is still one of the classic treatments for primary trigeminal...
Extracranial Non-Gasserian Ganglion Application of Radiofrequency Thermocoagulation on the Mandibular Branch of the Trigeminal through the Foramen Ovale for Trigeminal Neuralgia.
BACKGROUND
Percutaneous radiofrequency ablation (RFA) of the trigeminal Gasserian ganglion via the foramen ovale is still one of the classic treatments for primary trigeminal neuralgia. However, the Gasserian ganglion is deep in the middle cranial fossa. Although it is a structure outside the brain tissue, the puncture needle must enter the encephalic to reach the Gasserian ganglion and so it is difficult to completely avoid the risk of intracranial hemorrhage and infection caused by puncture damage to intracranial blood vessels. It is not clear whether if it is possible for RFA at the extracranial non-gasserian-ganglion site via the exit of the cranial channel (foramen ovale) for patients with V3 trigeminal neuralgia (TN).
STUDY DESIGN
Prospective, clinical research study.
SETTING
Department of Anesthesiology and Pain Medical Center, Jiaxing, China.
METHODS
One hundred and seven patients with isolated mandibular branch trigeminal neuralgia were included. Radiofrequency thermocoagulation was performed by CT-guided percutaneous puncture through the foramen ovale. The puncture target was the midpoint of the horizontal transverse diameter of the oval foramen. If the tingling sensation in the mandibular nerve innervation area could be detected, the radiofrequency thermocoagulation (90°C, 120 sec) under intravenous anesthesia would be performed. We investigated the inclination angle, puncture angle and depth, puncture operation time, intraoperative complications and short-term and long-term results after operation.
RESULTS
After radiofrequency thermocoagulation, the pain in the mandibular branch dominant area was completely diminished in 104 patients. Two patients were cured after the second radiofrequency treatment. No intracranial hemorrhage not infection complications occurred, except for facial hematoma during operation in 21 cases. After 12-24 months of follow-up, 9 patients had recurrence and were still effective after receiving additional extracranial radiofrequency treatment.
LIMITATIONS
A control group should be established and more clinical data should be collected in future work.
CONCLUSION
Extracranial non-Gasserian-ganglion RF can achieve satisfactory results and improve the safety of radiofrequency treatment for trigeminal neuralgia.
Topics: Electrocoagulation; Foramen Ovale; Humans; Prospective Studies; Trigeminal Ganglion; Trigeminal Neuralgia
PubMed: 34213867
DOI: No ID Found -
Scientific Reports Sep 2021Trigeminal (TG), dorsal root (DRG), and nodose/jugular (NG/JG) ganglia each possess specialized and distinct functions. We used RNA sequencing of two-cycle sorted...
Trigeminal (TG), dorsal root (DRG), and nodose/jugular (NG/JG) ganglia each possess specialized and distinct functions. We used RNA sequencing of two-cycle sorted Pirt-positive neurons to identify genes exclusively expressing in L3-L5 DRG, T10-L1 DRG, NG/JG, and TG mouse ganglion neurons. Transcription factor Phox2b and Efcab6 are specifically expressed in NG/JG while Hoxa7 is exclusively present in both T10-L1 and L3-L5 DRG neurons. Cyp2f2, Krt18, and Ptgds, along with pituitary hormone prolactin (Prl), growth hormone (Gh), and proopiomelanocortin (Pomc) encoding genes are almost exclusively in TG neurons. Immunohistochemistry confirmed selective expression of these hormones in TG neurons and dural nerves; and showed GH expression in subsets of TRPV1 and CGRP TG neurons. We next examined GH roles in hypersensitivity in the spinal versus trigeminal systems. Exogenous GH produced mechanical hypersensitivity when injected intrathecally, but not intraplantarly. GH-induced thermal hypersensitivity was not detected in the spinal system. GH dose-dependently generated orofacial and headache-like periorbital mechanical hypersensitivity after administration into masseter muscle and dura, respectively. Periorbital mechanical hypersensitivity was reversed by a GH receptor antagonist, pegvisomant. Overall, pituitary hormone genes are selective for TG versus other ganglia somatotypes; and GH has distinctive functional significance in the trigeminal versus spinal systems.
Topics: Animals; Ganglia, Spinal; Growth Hormone; Mice; Mice, Transgenic; Nodose Ganglion; Pain; Pro-Opiomelanocortin; Prolactin; Sensory Receptor Cells; Trigeminal Ganglion
PubMed: 34497285
DOI: 10.1038/s41598-021-97084-y -
The Journal of Neuroscience : the... Jul 2019Rodents are the most commonly studied model system in neuroscience, but surprisingly few studies investigate the natural sensory stimuli that rodent nervous systems...
Rodents are the most commonly studied model system in neuroscience, but surprisingly few studies investigate the natural sensory stimuli that rodent nervous systems evolved to interpret. Even fewer studies examine neural responses to these natural stimuli. Decades of research have investigated the rat vibrissal (whisker) system in the context of direct touch and tactile stimulation, but recent work has shown that rats also use their whiskers to help detect and localize airflow. The present study investigates the neural basis for this ability as dictated by the mechanical response of whiskers to airflow. Mechanical experiments show that a whisker's vibration magnitude depends on airspeed and the intrinsic shape of the whisker. Surprisingly, the direction of the whisker's vibration changes as a function of airflow speed: vibrations transition from parallel to perpendicular with respect to the airflow as airspeed increases. Recordings from primary sensory trigeminal ganglion neurons show that these neurons exhibit responses consistent with those that would be predicted from direct touch. Trigeminal neuron firing rate increases with airspeed, is modulated by the orientation of the whisker relative to the airflow, and is influenced by the whisker's resonant frequencies. We develop a simple model to describe how a population of neurons could leverage mechanical relationships to decode both airspeed and direction. These results open new avenues for studying vibrissotactile regions of the brain in the context of evolutionarily important airflow-sensing behaviors and olfactory search. Although this study used only female rats, all results are expected to generalize to male rats. The rodent vibrissal (whisker) system has been studied for decades in the context of direct tactile sensation, but recent work has indicated that rats also use whiskers to help localize airflow. Neural circuits in somatosensory regions of the rodent brain thus likely evolved in part to process airflow information. This study investigates the whiskers' mechanical response to airflow and the associated neural response. Airspeed affects the magnitude of whisker vibration and the response magnitude of whisker-sensitive primary sensory neurons in the trigeminal ganglion. Surprisingly, the direction of vibration and the associated directionally dependent neural response changes with airspeed. These findings suggest a population code for airflow speed and direction and open new avenues for studying vibrissotactile regions of the brain.
Topics: Animals; Female; Male; Physical Stimulation; Rats; Rats, Long-Evans; Touch Perception; Trigeminal Ganglion; Vibration; Vibrissae
PubMed: 31097620
DOI: 10.1523/JNEUROSCI.2971-18.2019