Connexin 43 expression in satellite glial cells contributes to ectopic tooth-pulp pain

Komiya, Hiroki; Shimizu, Kanichiro; Ishii, Keiichiro; Kudo, Hiroshi; Okamura, Teinosuke; Kanno, Kohei; Shinoda, Masamichi; Ogiso, Bunnai; Iwata, Koichi

doi:10.2334/josnusd.17-0452

Cited by 29 publications

(28 citation statements)

References 24 publications

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“…Most models are based on local injury to peripheral nerves, and include nerve section (axotomy) and tissue incision. Local inflammation models include chronic constriction injury or the application of substances such as carrageenan or complete Freund’s adjuvant to the paw 50 , face 46 and teeth 43 . Models of systemic pain include inflammation induced by lipopolysaccharide (LPS) 27 , 86 , neuropathy following systemic administration of anticancer drugs 23 and type 1 diabetes mellitus induced by streptozotocin (STZ) 87 – 89 .…”

Section: Sgcs In Selected Pain Conditionsmentioning

confidence: 99%

Emerging importance of satellite glia in nervous system function and dysfunction

2020

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Satellite glial cells (SGCs) closely envelop cell bodies of neurons in sensory, sympathetic and parasympathetic ganglia. This unique organization is not found elsewhere in the nervous system. SGCs in sensory ganglia are activated by numerous types of nerve injury and inflammation. The activation includes upregulation of glial fibrillary acidic protein, stronger gap junction-mediated SGC–SGC and neuron–SGC coupling, increased sensitivity to ATP, downregulation of Kir4.1 potassium channels and increased cytokine synthesis and release. There is evidence that these changes in SGCs contribute to chronic pain by augmenting neuronal activity and that these changes are consistent in various rodent pain models and likely also in human pain. Therefore, understanding these changes and the resulting abnormal interactions of SGCs with sensory neurons could provide a mechanistic approach that might be exploited therapeutically in alleviation and prevention of pain. We describe how SGCs are altered in rodent models of four common types of pain: systemic inflammation (sickness behaviour), post-surgical pain, diabetic neuropathic pain and post-herpetic pain.

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Section: Sgcs In Selected Pain Conditionsmentioning

confidence: 99%

Emerging importance of satellite glia in nervous system function and dysfunction

2020

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“…TRPA1 and Mrgprd have been linked in the development of mechanical allodynia in the lower body 29 , so some interaction could be involved in the dental pulp, particularly since TRPA1 is co-expressed in mechanosensitive dental pulp afferents 31 . Alternatively, paracrine signaling in the trigeminal ganglia via gap junction connections with satellite glia 40,41,44 could allow for recruitment of the non-peptidergic TLR4 negative MRGPRD population by the peptidergic TLR4+/TRPV1 and/or TRPA1+ cell populations to contribute to central mechanisms underlying the mechanical allodynia we observed.…”

Section: Discussionmentioning

confidence: 99%

Evoked and spontaneous pain assessment during tooth pulp injury

Rossi

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Foster

et al. 2020

Sci Rep

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injury of the tooth pulp is excruciatingly painful and yet the receptors and neural circuit mechanisms that transmit this form of pain remain poorly defined in both the clinic and preclinical rodent models. Easily quantifiable behavioral assessment in the mouse orofacial area remains a major bottleneck in uncovering molecular mechanisms that govern inflammatory pain in the tooth. In this study we sought to address this problem using the Mouse Grimace Scale and a novel approach to the application of mechanical Von frey hair stimuli. We use a dental pulp injury model that exposes the pulp to the outside environment, a procedure we have previously shown produces inflammation. Using RNAscope technology, we demonstrate an upregulation of genes that contribute to the pain state in the trigeminal ganglia of injured mice. We found that mice with dental pulp injury have greater Mouse Grimace Scores than sham within 24 hours of injury, suggestive of spontaneous pain. We developed a scoring system of mouse refusal to determine thresholds for mechanical stimulation of the face with Von Frey filaments. This method revealed that mice with a unilateral dental injury develop bilateral mechanical allodynia that is delayed relative to the onset of spontaneous pain. This work demonstrates that tooth pain can be quantified in freely behaving mice using approaches common for other types of pain assessment. Harnessing these assays in the orofacial area during gene manipulation should assist in uncovering mechanisms for tooth pulp inflammatory pain and other forms of trigeminal pain.

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“…The overlap of TRPA1 and Mrgprd in the tooth pulp afferents has not been explored. Alternatively, paracrine signaling in the trigeminal ganglia via gap junction connections with satellite glia 37,38,44 could allow for recruitment of the non-peptidergic TLR4 negative MRGPRD population by the peptidergic TLR4+/TRPV1 and/or TRPA1+ cell populations to produce the delayed mechanical allodynia we observed.…”

Section: Discussionmentioning

confidence: 99%

Evoked and spontaneous pain assessment during tooth pulp injury

Rossi

See

Foster

et al. 2019

Preprint

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Injury of the tooth pulp is excruciatingly painful and yet the receptors and neural circuit mechanisms that transmit this form of pain remain poorly defined in both the clinic and preclinical rodent models. Easily quantifiable behavioral assessment in the rodent orofacial area remains a major bottleneck in uncovering molecular mechanisms that govern inflammatory pain in the tooth. Here we use a dental pulp injury model in the mouse and expose the tooth pulp to the outside environment, a procedure we have previously shown produces pulpal inflammation. We demonstrate here with RNAscope technology in the trigeminal ganglion of injured mice, an upregulation of genes that contribute to the inflammatory pain state. Using both evoked and spontaneous measures of pain in the orofacial area, including application of von Frey Hair filaments and pain feature detection with the mouse grimace scale, we reveal a differential timeline of induction of spontaneous pain versus mechanical allodynia following pulpal injury. This work demonstrates that tooth pain can be easily assessed in freely behaving mice using approaches common for other types of pain assessment. Harnessing these assays in the orofacial area during gene manipulation should assist in uncovering mechanisms for tooth pulp inflammation and other forms of trigeminal pain. 11, eaal2171,

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Connexin 43 expression in satellite glial cells contributes to ectopic tooth-pulp pain

Cited by 29 publications

References 24 publications

Emerging importance of satellite glia in nervous system function and dysfunction

Emerging importance of satellite glia in nervous system function and dysfunction

Evoked and spontaneous pain assessment during tooth pulp injury

Evoked and spontaneous pain assessment during tooth pulp injury

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