Varied temporal expression patterns of trigeminal TRPA1 and TRPV1 and the neuropeptide CGRP during orthodontic force-induced pain

Thammanichanon, Peungchaleoy; Kaewpitak, Aunwaya; Binlateh, Thunwa; Pavasant, Prasit; Leethanakul, Chidchanok

doi:10.1016/j.archoralbio.2021.105170

Cited by 8 publications

(5 citation statements)

References 34 publications

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“…Indeed, TRPV1 is widely expressed in nociceptive primary sensory neurons of the trigeminal ganglia. 53 Previous studies showed an increased TRPV1 expression associated with the initial stages of force-induced orthodontic pain and an increased co-expression of TRPV1/CGRP in the trigeminal neurons. On the other hand, the antagonism of TRPV1 has been shown to have an analgesic effect in CARR-, CFA-, capsaicin- or acid-induced inflammatory pain.…”

Section: Discussionmentioning

confidence: 98%

Influence of TRPV1 on Thermal Nociception in Rats with Temporomandibular Joint Persistent Inflammation Evaluated by the Operant Orofacial Pain Assessment Device (OPAD)

Leite–Panissi¹,

Paula²,

Neubert³

et al. 2023

JPR

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Background T emporomandibular joint (TMJ)-associated inflammation contributes to the pain reported by patients with temporomandibular disorders (TMD). It is common for patients diagnosed with TMD to report pain in the masticatory muscles and temporomandibular joints, headache, and jaw movement disturbances. Although TMD can have different origins, including trauma and malocclusion disorder, anxiety/depression substantially impacts the development and maintenance of TMD. In general, rodent studies on orofacial pain mechanisms involve the use of tests originally developed for other body regions, which were adapted to the orofacial area. To overcome limitations and expand knowledge in orofacial pain, our group validated and characterized an operant assessment paradigm in rats with both hot and cold stimuli as well mechanical stimuli. Nevertheless, persistent inflammation of the TMJ has not been evaluated with this operant orofacial pain assessment device (OPAD). Methods We characterized the thermal orofacial sensitivity for cold, neutral, and hot stimuli during the development of TMD using the OPAD behavior test. In addition, we evaluated the role of transient receptor potential vanilloid 1 (TRPV1) expressing nociceptors in rats with persistent TMJ inflammation. The experiments were performed in male and female rats with TMJ inflammation induced by carrageenan (CARR). Additionally, resiniferatoxin (RTX) was administered into the TMJs prior CARR to lesion TRPV1-expressing neurons to evaluate the role of TRPV1-expressing neurons. Results We evidenced an increase in the number of facial contacts and changes in the number of reward licks per stimulus on neutral (37°C) and cold (21°C) temperatures. However, at the hot temperature (42°C), the inflammation did not induce changes in the OPAD test. The prior administration of RTX in the TMJ prevented the allodynia and thermal hyperalgesia induced by CARR. Conclusion We showed that TRPV-expressing neurons are involved in the sensitivity to carrageenan-induced pain in male and female rats evaluated in the OPAD.

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Section: Discussionmentioning

confidence: 98%

Influence of TRPV1 on Thermal Nociception in Rats with Temporomandibular Joint Persistent Inflammation Evaluated by the Operant Orofacial Pain Assessment Device (OPAD)

Leite–Panissi¹,

Paula²,

Neubert³

et al. 2023

JPR

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“…As mentioned above, CGRP release is promoted by the activation of the TRP channel family [ 76 ]. TRPV1 in the TG is primarily activated as an early response, whereas TRPA1 is activated as a late response to orofacial noxious stimulation [ 80 ]. Because several factors activate SGCs, and not CGRP alone [ 81 ], this suggests that the transient increase in SGC activation is an active process.…”

Section: Discussionmentioning

confidence: 99%

Effect of chronic intermittent hypoxia on ocular and intraoral mechanical allodynia mediated via the calcitonin gene-related peptide in a rat

Katagiri,

Kishimoto,

Okamoto

et al. 2023

Sleep

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Study Objectives Obstructive sleep apnea, a significant hypoxic condition, may exacerbate several orofacial pain conditions. The study aims to define the involvement of calcitonin gene-related peptide (CGRP) in peripheral and central sensitization and in evoking orofacial mechanical allodynia under chronic intermittent hypoxia (CIH). Methods Male rats were exposed to CIH. Orofacial mechanical allodynia was assessed using the eyeblink test and the two-bottle preference drinking test. The CGRP-immunoreactive neurons in the trigeminal ganglion (TG), CGRP-positive primary afferents projecting to laminae I–II of the trigeminal spinal subnucleus caudalis (Vc), and neural responses in the second-order neurons of the Vc were determined by immunohistochemistry. CGRP receptor antagonist was administrated in the TG. Results CIH induced ocular and intraoral mechanical allodynia. CGRP-immunoreactive neurons and activated satellite glial cells were significantly increased in the TG and the number of cFos-immunoreactive cells in laminae I–II of the Vc were significantly higher in CIH rats compared to normoxic rats. Local administration of the CGRP receptor antagonist in the TG of CIH rats attenuated orofacial mechanical allodynia; the number of CGRP-immunoreactive neurons and activated satellite glial cells in the TG, and the density of CGRP-positive primary afferent terminals and the number of cFos-immunoreactive cells in laminae I–II of the Vc were significantly lower compared to vehicle-administrated CIH rats. Conclusions An increase in CGRP in the TG induced by CIH, as well as orofacial mechanical allodynia and central sensitization of second-order neurons in the Vc, supported the notion that CGRP plays a critical role in CIH-induced orofacial mechanical allodynia.

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“…They also express mechanosensitive ion channels, which transduce sensations of pressure and stretching to the brain. These receptors and molecules, including TRPV1 ( 46 – 51 ), transient receptor potential ankyrin 1 (TRPA1) ( 47 , 48 , 52 ), Piezo1 ( 48 , 53 – 57 ), Piezo2 ( 48 , 53 ), acid-sensing ion channel 3 (ASIC3) ( 58 – 61 ), purinergic receptor (e.g., P2X3) ( 62 , 63 ), are discussed below.…”

Section: Primary Afferent Contributions To Orthodontic Painmentioning

confidence: 99%

“…Ca 2+ influx through TRPA1 in sensory neuronal soma and nerve terminals can induce the release of neuropeptides, promoting the inflammatory periodontal tissue response. The expression of TRPV1 increases in the TG within a day (as an early response), while the upregulation of TRPA1 gradually increases from day one to day three as a late response during experimental tooth movement in rats ( 47 ). Therefore, the combined inhibition of TRPV1 and TRPA1 can additively attenuate orthodontic pain.…”

Section: Role Of Ion Channels In Periodontal Nociceptors In Orthodont...mentioning

confidence: 99%

“…Inflammation induced by tooth movement sensitizes TRPV1 and TRPA1 in the primary afferent terminals ( 52 ). Activation of TRPV1, as an early response, and TRPA1, as a late response, results in CGRP release at the end of neuronal axons in vesicles through exocytosis ( 47 ). CGRP released from periodontal afferent terminals into the periodontal tissue plays the roles of vasodilator and transmitter for nociceptive information.…”

Section: Role Of Neuropeptides In Orthodontic Painmentioning

confidence: 99%

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Nociceptor mechanisms underlying pain and bone remodeling via orthodontic forces: toward no pain, big gain

Wang,

Ko,

Chung

2024

Front. Pain Res.

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Orthodontic forces are strongly associated with pain, the primary complaint among patients wearing orthodontic braces. Compared to other side effects of orthodontic treatment, orthodontic pain is often overlooked, with limited clinical management. Orthodontic forces lead to inflammatory responses in the periodontium, which triggers bone remodeling and eventually induces tooth movement. Mechanical forces and subsequent inflammation in the periodontium activate and sensitize periodontal nociceptors and produce orthodontic pain. Nociceptive afferents expressing transient receptor potential vanilloid subtype 1 (TRPV1) play central roles in transducing nociceptive signals, leading to transcriptional changes in the trigeminal ganglia. Nociceptive molecules, such as TRPV1, transient receptor potential ankyrin subtype 1, acid-sensing ion channel 3, and the P2X3 receptor, are believed to mediate orthodontic pain. Neuropeptides such as calcitonin gene-related peptides and substance P can also regulate orthodontic pain. While periodontal nociceptors transmit nociceptive signals to the brain, they are also known to modulate alveolar bone remodeling in periodontitis. Therefore, periodontal nociceptors and nociceptive molecules may contribute to the modulation of orthodontic tooth movement, which currently remains undetermined. Future studies are needed to better understand the fundamental mechanisms underlying neuroskeletal interactions in orthodontics to improve orthodontic treatment by developing novel methods to reduce pain and accelerate orthodontic tooth movement—thereby achieving “big gains with no pain” in clinical orthodontics.

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Varied temporal expression patterns of trigeminal TRPA1 and TRPV1 and the neuropeptide CGRP during orthodontic force-induced pain

Cited by 8 publications

References 34 publications

Influence of TRPV1 on Thermal Nociception in Rats with Temporomandibular Joint Persistent Inflammation Evaluated by the Operant Orofacial Pain Assessment Device (OPAD)

Influence of TRPV1 on Thermal Nociception in Rats with Temporomandibular Joint Persistent Inflammation Evaluated by the Operant Orofacial Pain Assessment Device (OPAD)

Effect of chronic intermittent hypoxia on ocular and intraoral mechanical allodynia mediated via the calcitonin gene-related peptide in a rat

Nociceptor mechanisms underlying pain and bone remodeling via orthodontic forces: toward no pain, big gain

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