Etidronate attenuates tactile allodynia by spinal ATP release inhibition in mice with partial sciatic nerve ligation

Yamagata, Ryota; Nemoto, Wataru; Nakagawasai, Osamu; Hung, Wan-Yi; Shima, Kazuhiro; Endo, Yasuo; Tan-No, Koichi

doi:10.1007/s00210-018-1593-2

Cited by 7 publications

(9 citation statements)

References 21 publications

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“…Interestingly, inhibition of VNUT has also been implicated in the inhibitory effect of clodronate in mechanical allodynia induced by Candida albicans ‐derived β‐glucan (Maruyama et al, 2018). Despite the relatively moderate inhibitory effects of etidronate on VNUT seen by Kato et al (2017), Yamagata et al (2018) implicated this mechanism in the anti‐allodynic effects of etidronate in a neuropathic pain model. They found a specific increase of SLC17A9 (VNUT) mRNA and protein levels in superficial dorsal horn neurons and microglia of lumbar spinal cord after partial spinal nerve ligation surgery.…”

Section: Putative Analgesic Mechanisms Of Action Of Bisphosphonatesmentioning

confidence: 99%

“…Pre-emptive treatment was most effective to prevent joint degeneration and to restore weight-bearing deficits; when treatment commenced shortly after OA induction, these effects were still present but reduced. When treatment commenced 3-4 weeks after OA induction, the effects were further reduced Strassle et al (2010) MIA Dose-dependent reduction of tactile allodynia with both routes of administration Yamagata et al (2018) CCI (rat) Alendronate (4, 10, and 20 μg•kg −1 i.t. once daily for 7 days and 0.1, 1, and 5 mg•kg −1 i.p.…”

Section: Bjpmentioning

confidence: 99%

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Pharmacology of bisphosphonates in pain

Tzschentke

2019

British J Pharmacology

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Section: Putative Analgesic Mechanisms Of Action Of Bisphosphonatesmentioning

confidence: 99%

Section: Bjpmentioning

confidence: 99%

Pharmacology of bisphosphonates in pain

Tzschentke

2019

British J Pharmacology

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“…SLC17A9/VNUT-dependent ATP release from dorsal horn neurons is an essential mechanism of tactile allodynia in neuropathic pain after peripheral nerve injury, 8 , 9 and peripheral nerve injury is reported to increase SLC17A9 expression in the spinal cord in rodents. 15 , 17 In humans, carriers of the minor allele of the rs735055 SNP have high mRNA expression in the spinal cord, 31 which may cause high SLC17A9 expression and facilitate the efficient storage and release of ATP.…”

Section: Discussionmentioning

confidence: 99%

“… 7 Purinergic receptor P2Y12 (P2RY12) is expressed on satellite glial cells, and the purinergic receptor P2X4 is expressed on MLCs. 7 In the spinal cord, SLC17A9-dependent ATP release from dorsal horn neurons 8 , 9 and high P2RY12 expression in microglia 10 , 11 have been reported to be involved in neuropathic pain.…”

Section: Introductionmentioning

confidence: 99%

Single-nucleotide polymorphisms of the SLC17A9 and P2RY12 genes are significantly associated with phantom tooth pain

et al. 2022

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Phantom tooth pain (PTP) is a rare and specific neuropathic pain that occurs after pulpectomy and tooth extraction, but its cause is not understood. We hypothesized that there is a genetic contribution to PTP. We focused on solute carrier family 17 member 9 (SLC17A9)/vesicular nucleotide transporter (VNUT) and purinergic receptor P2Y12 (P2RY12), both of which have been associated with neuropathic pain and pain transduction signaling in the trigeminal ganglion in rodents. We sought to corroborate these associations in humans. We investigated gene polymorphisms that contribute to PTP. We statistically examined the association between genetic polymorphisms and PTP vulnerability in 150 patients with orofacial pain, including PTP, and 500 healthy subjects. We found that the rs735055 polymorphism of the SLC17A9 gene and rs3732759 polymorphism of the P2RY12 gene were associated with the development of PTP. Carriers of the minor allele of rs735055 and individuals who were homozygous for the major allele of rs3732759 had a higher rate of PTP. Carriers of the minor allele of rs735055 reportedly had high SLC17A9 mRNA expression in the spinal cord, which may increase the storage and release of adenosine triphosphate. Individuals who were homozygous for the major allele of rs3732759 may have higher P2RY12 expression that is more active in microglia. Therefore, these carriers may be more susceptible to PTP. These results suggest that specific genetic polymorphisms of the SLC17A9 and P2RY12 genes are involved in PTP. This is the first report on genes that are associated with PTP in humans.

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“…Clodronate and etidronate are biphosphonates used in osteoporosis therapy that have analgesic properties. In vitro assays demonstrated that they inhibited VNUT, leading to the modulation of ATP release and purinergic transmission [ 157 , 158 ]. In addition, in vivo studies with clodronate showed attenuation of neuropathic and inflammatory pain [ 158 ].…”

Section: Perspectives Of Atp and Adenosine Signaling Modulation: Pmentioning

confidence: 99%

Purinergic Signaling in Endometriosis-Associated Pain

Trapero

Martı́n-Satué

2020

IJMS

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Endometriosis is an estrogen-dependent gynecological disease, with an associated chronic inflammatory component, characterized by the presence of endometrial tissue outside the uterine cavity. Its predominant symptom is pain, a condition notably altering the quality of life of women with the disease. This review is intended to exhaustively gather current knowledge on purinergic signaling in endometriosis-associated pain. Altered extracellular ATP hydrolysis, due to changes in ectonucleotidase activity, has been reported in endometriosis; the resulting accumulation of ATP in the endometriotic microenvironment points to sustained activation of nucleotide receptors (P2 receptors) capable of generating a persistent pain message. P2X3 receptor, expressed in sensory neurons, mediates nociceptive, neuropathic, and inflammatory pain, and is enrolled in endometriosis-related pain. Pharmacological inhibition of P2X3 receptor is under evaluation as a pain relief treatment for women with endometriosis. The role of other ATP receptors is also discussed here, e.g., P2X4 and P2X7 receptors, which are involved in inflammatory cell–nerve and microglia–nerve crosstalk, and therefore in inflammatory and neuropathic pain. Adenosine receptors (P1 receptors), by contrast, mainly play antinociceptive and anti-inflammatory roles. Purinome-targeted drugs, including nucleotide receptors and metabolizing enzymes, are potential non-hormonal therapeutic tools for the pharmacological management of endometriosis-related pain.

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Etidronate attenuates tactile allodynia by spinal ATP release inhibition in mice with partial sciatic nerve ligation

Cited by 7 publications

References 21 publications

Pharmacology of bisphosphonates in pain

Pharmacology of bisphosphonates in pain

Single-nucleotide polymorphisms of the SLC17A9 and P2RY12 genes are significantly associated with phantom tooth pain

Purinergic Signaling in Endometriosis-Associated Pain

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