Expression of Ecto-ATPase NTPDase2 in Human Dental Pulp

Liu, X.; Yu, Luyang; Wang, Q.; Pelletier, Julie; Fausther, Michel; Sévigny, Jean; Malmström, Hans; Dirksen, Robert T.; Ren, Yan-Fang

doi:10.1177/0022034511431582

Cited by 35 publications

(46 citation statements)

References 39 publications

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“…Furthermore, external mechanical and thermal stimulation that mimics dentin hypersensitivity induces ATP release in a tooth perfusion model, while pharmacological blocking connexin and pannexin channels abolished external stimulation-induced ATP release in dental pulp [66]. Based on the above observations, we proposed that, as illustrated in Figure 2, external stimulation-induced mechanosensitive responses and ATP release from odontoblasts and subsequently activation of purinergic receptors in dental pulpal nerves may represent a novel explanation as to how odontoblasts participate in a mechanosensory mechanism leading to the pain transduction in DHS [60,74].…”

Section: The Machinery For Atp Signaling In Dental Pulpmentioning

confidence: 73%

“…How the essentially non-noxious dentin tubule fluid movements induce the nociceptive transduction in dental pulpal nerve fibers remains an enigma. Recently, the hydrodynamic theory has been challenged by emerging evidence suggesting that odontoblasts might play an essential role in the nociceptive transduction of DHS [60][61][62].…”

Section: Hydrodynamic Theorymentioning

confidence: 99%

“…For the past decades, chemo-, mechano-, and or thermo-sensitive channels such as connexin, pannexin, TRPV1-4, TRPM3, KCa, TREK-1, beta-ENa(+) C, and ASIC2 channels have been identified in odontoblasts [60,[65][66][67][68][69][70]. Activation of these channels depolarizes the membrane potential that induces ATP release via vesicles release or channel opening in odontoblasts.…”

Section: The Machinery For Atp Signaling In Dental Pulpmentioning

confidence: 99%

“…Activation of these channels depolarizes the membrane potential that induces ATP release via vesicles release or channel opening in odontoblasts. Interestingly, mechanicas well as depolarization-sensitive ATP permeable channel such as connexin 43 and pannexins had been detected in odontoblastic processes inserting into dentinal tubules [60,64]. Indeed it has been shown that mechanical and or thermal stimulation that mimics dentin hypersensitivity in clinic induces ATP release from odontoblasts [65,66,71].…”

Section: The Machinery For Atp Signaling In Dental Pulpmentioning

confidence: 99%

“…For example, a local mechanical stimulation induces connexin/pannexin channel opening, and then result in ATP release, ATP then activates the P2X/P2Y receptors in adjacent cells inducing intracellular Ca 2+ increase and/or cell depolarization that further promote connexin/pannexin channels opening and ATP release in further beyond adjacent cells until all the cells are activated. Since odontoblasts express connexin 43 and are functionally connected via gap junction as a syncytium [60,76], stimulation from locally exposed dentin tubules will induce a response in the whole dental pulp odontoblasts. With this mechanism, external stimulation will cause the full dental pulp odontoblast activation and evoke the typical "all" or "none" short, sharp pain in patients with DHS.…”

Section: Purinergic Signaling and Dentin Hypersensitivitymentioning

confidence: 99%

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Purinergic Signaling and Dental Orofacial Pain

Liu¹

2020

Receptors P1 and P2 as Targets for Drug Therapy in Humans

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Pain is a common complaint of patients in the dental clinic. Patient with dental orofacial pain usually presents with hyperalgesia and allodynia. Its management has been a challenge, especially in the status of chronic pain or neuropathic pain. Purinergic signaling is dictated by ATP release, purinergic receptors activation, and sequential hydrolysis of ATP. Purinergic signaling participates in nociception processing in the sensory nerves by control of pain signal transduction, modulation, and sensitization. Since purinergic receptors are preferentially expressed in trigeminal nerves, purinergic singling may play a crucial role in the development of dental orofacial pain. In this chapter, we overview the expressions of purinergic receptors as well as the machinery for ATP release, ATP degradations, and adenosine generation in trigeminal nerves. Specifically, the roles of ATP signaling in dental orofacial pain generation and central sensitization via activation of P2 receptors and adenosine signaling in analgesia via activation of P1 receptors in trigeminal nerves are updated. We also discuss the affection of ecto-nucleotidases, the major enzymes responsible for extracellular ATP degradation and adenosine generation in trigeminal nerves that drive the shift from ATP-induced pain to adenosine-induced analgesia. This chapter provides advanced outlines for purinergic signaling in trigeminal nerves and unveils potential therapeutic targets for the management of dental orofacial pain.

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Section: The Machinery For Atp Signaling In Dental Pulpmentioning

confidence: 73%

Section: Hydrodynamic Theorymentioning

confidence: 99%

Section: The Machinery For Atp Signaling In Dental Pulpmentioning

confidence: 99%

Section: The Machinery For Atp Signaling In Dental Pulpmentioning

confidence: 99%

Section: Purinergic Signaling and Dentin Hypersensitivitymentioning

confidence: 99%

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Purinergic Signaling and Dental Orofacial Pain

Liu¹

2020

Receptors P1 and P2 as Targets for Drug Therapy in Humans

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Immunoelectron microscopic observation of connexin43 in rat odontoblasts

Muramatsu

Hashimoto

Shibukawa

et al. 2013

Microscopy Res & Technique

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Gap junctions play an important role in differentiation of odontoblasts. Gap junction protein, connexin 43 is expressed in odontoblast. However, the detailed localization in odontoblasts has yet to be fully investigated. We investigated the localization of connexin43 in rat odontoblasts immuno-electron microscopically. The rats were transcardially fixed with 1% paraformaldehyde in 0.1M phosphate buffer, and mandibles were decalcified with 10% ethylenediamine tetraacetic acid. Pre-embedding method was carried out for immuno-electron microscopic analysis. Microscopically, gap junctions were localized between bodies of odontoblasts, and between bodies and processes of odontoblasts. The gap junctions were labeled with gold particles that indicated connexin43. These results suggest that gap junctions between odontoblasts are definitely composed of connexin43 in rats, and our methods used in this study is useful to investigate localization of connexin43 immuno-electron microscopically.

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Odontoblasts as sensory receptors: transient receptor potential channels, pannexin-1, and ionotropic ATP receptors mediate intercellular odontoblast-neuron signal transduction

Shibukawa

Sato

Kimura

et al. 2014

Pflugers Arch - Eur J Physiol

174

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Various stimuli induce pain when applied to the surface of exposed dentin. However, the mechanisms underlying dentinal pain remain unclear. We investigated intercellular signal transduction between odontoblasts and trigeminal ganglion (TG) neurons following direct mechanical stimulation of odontoblasts. Mechanical stimulation of single odontoblasts increased the intracellular free calcium concentration ([Ca(2+)]i) by activating the mechanosensitive-transient receptor potential (TRP) channels TRPV1, TRPV2, TRPV4, and TRPA1, but not TRPM8 channels. In cocultures of odontoblasts and TG neurons, increases in [Ca(2+)]i were observed not only in mechanically stimulated odontoblasts, but also in neighboring odontoblasts and TG neurons. These increases in [Ca(2+)]i were abolished in the absence of extracellular Ca(2+) and in the presence of mechanosensitive TRP channel antagonists. A pannexin-1 (ATP-permeable channel) inhibitor and ATP-degrading enzyme abolished the increases in [Ca(2+)]i in neighboring odontoblasts and TG neurons, but not in the stimulated odontoblasts. G-protein-coupled P2Y nucleotide receptor antagonists also inhibited the increases in [Ca(2+)]i. An ionotropic ATP (P2X3) receptor antagonist inhibited the increase in [Ca(2+)]i in neighboring TG neurons, but not in stimulated or neighboring odontoblasts. During mechanical stimulation of single odontoblasts, a connexin-43 blocker did not have any effects on the [Ca(2+)]i responses observed in any of the cells. These results indicate that ATP, released from mechanically stimulated odontoblasts via pannexin-1 in response to TRP channel activation, transmits a signal to P2X3 receptors on TG neurons. We suggest that odontoblasts are sensory receptor cells and that ATP released from odontoblasts functions as a neurotransmitter in the sensory transduction sequence for dentinal pain.

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Expression of Ecto-ATPase NTPDase2 in Human Dental Pulp

Cited by 35 publications

References 39 publications

Purinergic Signaling and Dental Orofacial Pain

Purinergic Signaling and Dental Orofacial Pain

Immunoelectron microscopic observation of connexin43 in rat odontoblasts

Odontoblasts as sensory receptors: transient receptor potential channels, pannexin-1, and ionotropic ATP receptors mediate intercellular odontoblast-neuron signal transduction

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