2014
DOI: 10.3390/toxins6082363
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Synthesis and Analgesic Effects of μ-TRTX-Hhn1b on Models of Inflammatory and Neuropathic Pain

Abstract: μ-TRTX-Hhn1b (HNTX-IV) is a 35-amino acid peptide isolated from the venom of the spider, Ornithoctonus hainana. It inhibits voltage-gated sodium channel Nav1.7, which has been considered as a therapeutic target for pain. The goal of the present study is to elucidate the analgesic effects of synthetic μ-TRTX-Hhn1b on animal models of pain. The peptide was first synthesized and then successfully refolded/oxidized. The synthetic peptide had the same inhibitory effect on human Nav1.7 current transiently expressed … Show more

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Cited by 39 publications
(29 citation statements)
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“…Various analgesic toxins have been proposed as candidates to replace opioids, because of their well-known side-effects. Hence, HwTx-IV, HnTx-IV, Pn3a and ProTx-II were shown to decrease pain at the level of morphine relief, in a dose-depending manner, in neuropathic (mainly spared nerve injury and diabetic neuropathy) and all inflammatory pain models, revealing a real evidence of their analgesic potential as drugs ( Liu et al, 2014a , b , Tanaka et al, 2015 ; Deuis et al, 2017a ; Flinspach et al, 2017 ). Pn3a and the ProTx-II mutant JNJ63955918 were also described as being effective on acute thermal pain tests ( Deuis et al, 2017a ; Flinspach et al, 2017 ).…”
Section: Analgesic Spider Toxins Targeting the Na V mentioning
confidence: 94%
“…Various analgesic toxins have been proposed as candidates to replace opioids, because of their well-known side-effects. Hence, HwTx-IV, HnTx-IV, Pn3a and ProTx-II were shown to decrease pain at the level of morphine relief, in a dose-depending manner, in neuropathic (mainly spared nerve injury and diabetic neuropathy) and all inflammatory pain models, revealing a real evidence of their analgesic potential as drugs ( Liu et al, 2014a , b , Tanaka et al, 2015 ; Deuis et al, 2017a ; Flinspach et al, 2017 ). Pn3a and the ProTx-II mutant JNJ63955918 were also described as being effective on acute thermal pain tests ( Deuis et al, 2017a ; Flinspach et al, 2017 ).…”
Section: Analgesic Spider Toxins Targeting the Na V mentioning
confidence: 94%
“…Small-molecule peptide blockers of Na v 1.7 (for example, m-TRTX-Hhn1b derived from spider venom or m-SLPTX-Ssm6a from centipede venom) are also of interest Liu et al, 2014). A monoclonal antibody targeting the voltage sensor paddle domain of Nav1.7 is available to allow for greater sodium channel subtype selectivity .…”
Section: Role Of Ectopic Activity In Primary Afferent Fibersmentioning
confidence: 99%
“…Use of a Na V 1.7-specific antagonist in a rodent model of abdominal inflammation was noted to reduce pain scores. 62 Na V 1.7 mRNA expression was shown to increase in lower lumbar DRG neurons in the setting of a chronic stress 63 and colitis models 64 in rats. However, another study utilizing a conditional nociceptor-specific Na V 1.7 knockout mouse model and selective Na V 1.7…”
Section: Na V 17mentioning
confidence: 96%
“…Animal studies investigating the role of Na V 1.7 in visceral pain perception have demonstrated somewhat conflicting results. Use of a Na V 1.7‐specific antagonist in a rodent model of abdominal inflammation was noted to reduce pain scores . Na V 1.7 mRNA expression was shown to increase in lower lumbar DRG neurons in the setting of a chronic stress and colitis models in rats.…”
Section: The Influence Of Voltage‐gated Sodium Channels (Vgscs) On Gamentioning
confidence: 99%