Analgesic effects of the CTK 01512-2 toxin in different models of orofacial pain in rats

Caminski, Emanuelle Sistherenn; Freitas, Leandro Mendes de; Dallegrave, Eliane; Silva, Claudio Antônio da; Gomez, Marcus V.; Pereira, Elizete Maria Rita; Antunes, Flavia Tasmin Techera; Souza, Alessandra Hübner de

doi:10.1007/s43440-020-00108-z

Cited by 15 publications

(10 citation statements)

References 49 publications

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“…We used two models here in order to confirm the relevance of TRPA1 in TMD-induced pain/arthritis. Independently, a combined TRPA1 antagonist and the selective inhibitor of the N-type voltage-gated calcium channels has very recently been shown to attenuate TRPA1-mediated facial grooming in a CFA-induced rat TMJ model [27], and our results build on that finding. A link between zymosan and TRPA1-induced nociception is also established in inflammatory models associated with pain [28,29].…”

Section: Discussionsupporting

confidence: 79%

Evidence That a TRPA1-Mediated Murine Model of Temporomandibular Joint Pain Involves NLRP3 Inflammasome Activation

et al. 2021

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This study investigates the role of transient receptor potential ankyrin 1 (TRPA1) in murine temporomandibular joint (TMJ) inflammatory hyperalgesia and the influence of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome. Two distinct murine models of TMJ pain and inflammation (zymosan and CFA) were established. Spontaneous pain-like behaviours were observed as unilateral front paw cheek wipes. Ipsilateral cheek blood flow was used as a measure of ongoing inflammation, which, to our knowledge, is a novel approach to assessing real-time inflammation in the TMJ. Joint tissue and trigeminal ganglia were collected for ex vivo investigation. Both zymosan and CFA induced a time-dependent increase in hyperalgesia and inflammation biomarkers. Zymosan induced a significant effect after 4 h, correlating with a significantly increased IL-1β protein expression. CFA (50 µg) induced a more sustained response. The TRPA1 receptor antagonist A967079 significantly inhibited hyper-nociception. The NLRP3 inhibitor MCC950 similarly inhibited hyper-nociception, also attenuating inflammatory markers. In the trigeminal ganglia, CFA-induced CGRP expression showed trends of inhibition by A967079, whilst lba1 immunofluorescence was significantly inhibited by A967079 and MCC950, where the effect of TRPA1 inhibition lasted up to 14 days. Our results show that stimulation of TRPA1 is key to the TMJ pain. However, the inflammasome inhibitor exhibited similar properties in attenuating these pain-like behaviours, in addition to some inflammatory markers. This indicates that in addition to the therapeutic targeting of TRPA1, NLRP3 inhibition may provide a novel therapeutic strategy for TMJ inflammation and pain.

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Section: Discussionsupporting

confidence: 79%

Evidence That a TRPA1-Mediated Murine Model of Temporomandibular Joint Pain Involves NLRP3 Inflammasome Activation

et al. 2021

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“…It was shown recently that calcium channels blockers' toxins attenuated abdominal hyperalgesia and in ammatory response associated with the cerulein-induced acute pancreatitis in rats [22]. The recombinant peptide also showed analgesic effects in orofacial pain models [21] and neuroprotective effects against neurotoxicity induced by 3-nitropropionic acid in rats [26]. In a model of multiple sclerosis, CTK 01512-2 signi cantly improved the neuroin ammatory with a higher e cacy when compared to ziconotide [12].…”

Section: Discussionmentioning

confidence: 99%

“…To block the VGCCs, the channelactivating current must be disrupted, whereby the blockers and the toxins normally act by modulating the G-protein-coupled receptors [18,19,17]. CTK 01512-2 toxin has proved to have a therapeutically potential in preclinical studies of pain models, such as in ammatory [20][21][22][23][24], neuropathic [13,25,24], energy metabolism and cell death [26], cancer [27][28][29], multiple sclerosis [12], and bromyalgia [30,31]. Based on previous ndings, herein, we have investigated whether CTK 01512-2 central and systemic treatments can produce analgesic and anti-in ammatory effects in both CPIP and neuropathy induced by paclitaxel models in order to provide further evidence on its related pain mechanisms.…”

Section: Introductionmentioning

confidence: 99%

The Antihyperalgesic Effects of the Calcium Channel Blocker CTK 01512-2 Toxin in Persistent Pain Models

Cavalli

Gonçalves

Bobermin

et al. 2021

Preprint

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The CTK 01512-2 toxin is a recombinant peptide of the Phα1β version derived from the venom of the Phoneutria nigriventer spider. It is an N-type voltage-gated calcium channel (VGCC) blocker showing a prolonged effect on the prevention and reduction of nociception. Herein, CTK 01512-2 toxin was tested in two models of persistent pain, the chronic post-ischemia pain (CPIP) and the peripheral neuropathy induced by paclitaxel, to evaluate its intrathecal, systemic, and intracerebroventricular effects on mechanical hypersensitivity and thermal allodynia. The astroglial cell viability using the MTT test was also investigated. The results showed that CTK 01512-2 intrathecal and systemic treatments reduced mechanical hypersensitivity induced by CPIP, mainly between 1 – 4 h after CTK 01512-2 administration. When the CTK 01512-2 intrathecal treatment was applied, it also reduced the thermal allodynia induced by CPIP. CTK 01512-2 intracerebroventricular treatment also showed mechanical antihyperalgesic and thermal antiallodynic effects in the peripheral neuropathy induced by paclitaxel, reinforcing CTK 01512-2 therapeutically potential to treat persistent pain conditions. CTK 01512-2 further altered the astroglial cell viability in the MTT reduction assay, which may indicate its effects on the mitochondrial activity of these cells, possibly as a compensatory mechanism on calcium signaling. The current study shows CTK 01512-2 antihyperalgesic effects in persistent pain models, helping to pave new perspectives of pain relief treatments to patients affected by peripheral neuropathy and chronic pain conditions.

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“…Blocking TRPA1 can inhibit mechanical pain 83 . For example, HC‐030031 blocking TRPA1 can reduce the pain caused by orthodontic tooth movement in the rat model 81,84,85 …”

Section: Mechanismmentioning

confidence: 99%

Molecular mechanism in trigeminal nerve and treatment methods related to orthodontic pain

Tang

Long

Gao

et al. 2021

J of Oral Rehabilitation

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Background Orthodontic treatment is the main treatment approach for malocclusion. Orthodontic pain is an inevitable undesirable adverse reaction during orthodontic treatment. It is reported orthodontic pain has become one of the most common reason that patients withdraw from orthodontic treatment. Therefore, understanding the underlying mechanism and finding treatment of orthodontic pain are in urgent need. Aims This article aims to sort out the mechanisms and treatments of orthodontic pain, hoping to provide some ideas for future orthodontic pain relief. Materials Tooth movement will cause local inflammation. Certain inflammatory factors and cytokines stimulating the trigeminal nerve and further generating pain perception, as well as drugs and molecular targeted therapy blocking nerve conduction pathways, will be reviewed in this article. Method We review and summaries current studies related to molecular mechanisms and treatment approaches in orthodontic pain control. Results Orthodontics pain related influencing factors and molecular mechanisms has been introduced. Commonly used clinical methods in orthodontic pain control has been evaluated. Discussion With the clarification of more molecular mechanisms, the direction of orthodontic pain treatment will shift to targeted drugs.

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Analgesic effects of the CTK 01512-2 toxin in different models of orofacial pain in rats

Cited by 15 publications

References 49 publications

Evidence That a TRPA1-Mediated Murine Model of Temporomandibular Joint Pain Involves NLRP3 Inflammasome Activation

Evidence That a TRPA1-Mediated Murine Model of Temporomandibular Joint Pain Involves NLRP3 Inflammasome Activation

The Antihyperalgesic Effects of the Calcium Channel Blocker CTK 01512-2 Toxin in Persistent Pain Models

Molecular mechanism in trigeminal nerve and treatment methods related to orthodontic pain

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