scholarly journals Tetrodotoxin, a Potential Drug for Neuropathic and Cancer Pain Relief?

Toxins ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 483
Author(s):  
Rafael González-Cano ◽  
M. Carmen Ruiz-Cantero ◽  
Miriam Santos-Caballero ◽  
Carlos Gómez-Navas ◽  
Miguel Á. Tejada ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sensory Neurons ◽  
Therapeutic Potential ◽  
Primary Sensory Neurons ◽  
Loss Of Function ◽  
Natural Toxins ◽  
Voltage Gated Sodium Channels ◽  
Puffer Fish ◽  
Pathological Pain ◽  
Therapeutic Doses

Tetrodotoxin (TTX) is a potent neurotoxin found mainly in puffer fish and other marine and terrestrial animals. TTX blocks voltage-gated sodium channels (VGSCs) which are typically classified as TTX-sensitive or TTX-resistant channels. VGSCs play a key role in pain signaling and some TTX-sensitive VGSCs are highly expressed by adult primary sensory neurons. During pathological pain conditions, such as neuropathic pain, upregulation of some TTX-sensitive VGSCs, including the massive re-expression of the embryonic VGSC subtype NaV1.3 in adult primary sensory neurons, contribute to painful hypersensitization. In addition, people with loss-of-function mutations in the VGSC subtype NaV1.7 present congenital insensitive to pain. TTX displays a prominent analgesic effect in several models of neuropathic pain in rodents. According to this promising preclinical evidence, TTX is currently under clinical development for chemo-therapy-induced neuropathic pain and cancer-related pain. This review focuses primarily on the preclinical and clinical evidence that support a potential analgesic role for TTX in these pain states. In addition, we also analyze the main toxic effects that this neurotoxin produces when it is administered at therapeutic doses, and the therapeutic potential to alleviate neuropathic pain of other natural toxins that selectively block TTX-sensitive VGSCs.

scholarly journals Toll-like receptor 7 contributes to neuropathic pain by activating NF-κB in primary sensory neurons

2020 ◽  
Vol 87 ◽  
pp. 840-851 ◽  
Author(s):  
Long He ◽  
Guang Han ◽  
Shaogen Wu ◽  
Shibin Du ◽  
Yang Zhang ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sensory Neurons ◽  
Primary Sensory Neurons ◽  
Toll Like Receptor

Up-regulation of cholecystokinin in primary sensory neurons is associated with morphine insensitivity in experimental neuropathic pain in the rat

Neuropeptides ◽  
1993 ◽  
Vol 24 (4) ◽  
pp. 218
Author(s):  
Z. Wiesenfeld-Hallin ◽  
T. Hökfelt ◽  
J. Hughes ◽  
M.J.C. Puke ◽  
V.M.K. Verge ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sensory Neurons ◽  
Primary Sensory Neurons

scholarly journals Neuropathic Pain Develops Normally in Mice Lacking both Nav1.7 and Nav1.8

2005 ◽  
Vol 1 ◽  
pp. 1744-8069-1-24 ◽  
Author(s):  
Mohammed A Nassar ◽  
Alessandra Levato ◽  
L Caroline Stirling ◽  
John N Wood
Keyword(s):  
Neuropathic Pain ◽  
Sodium Channels ◽  
Sensory Neurons ◽  
Inflammatory Pain ◽  
Pain Thresholds ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Pain Symptoms ◽  
Α Subunits

Two voltage gated sodium channel α-subunits, Nav1.7 and Nav1.8, are expressed at high levels in nociceptor terminals and have been implicated in the development of inflammatory pain. Mis-expression of voltage-gated sodium channels by damaged sensory neurons has also been implicated in the development of neuropathic pain, but the role of Nav1.7 and Nav1.8 is uncertain. Here we show that deleting Nav1.7 has no effect on the development of neuropathic pain. Double knockouts of both Nav1.7 and Nav1.8 also develop normal levels of neuropathic pain, despite a lack of inflammatory pain symptoms and altered mechanical and thermal acute pain thresholds. These studies demonstrate that, in contrast to the highly significant role for Nav1.7 in determining inflammatory pain thresholds, the development of neuropathic pain does not require the presence of either Nav1.7 or Nav1.8 alone or in combination.

scholarly journals Up-regulation of Cavβ3Subunit in Primary Sensory Neurons Increases Voltage-activated Ca2+Channel Activity and Nociceptive Input in Neuropathic Pain

2011 ◽  
Vol 287 (8) ◽  
pp. 6002-6013 ◽  
Author(s):  
Li Li ◽  
Xue-Hong Cao ◽  
Shao-Rui Chen ◽  
Hee-Dong Han ◽  
Gabriel Lopez-Berestein ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sensory Neurons ◽  
Primary Sensory Neurons ◽  
Channel Activity ◽  
Nociceptive Input

scholarly journals The Calcium Channel α2δ1 Subunit: Interactional Targets in Primary Sensory Neurons and Role in Neuropathic Pain

2021 ◽  
Vol 15 ◽  
Author(s):  
Wenqiang Cui ◽  
Hongyun Wu ◽  
Xiaowen Yu ◽  
Ting Song ◽  
Xiangqing Xu ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Calcium Channel ◽  
Sensory Neurons ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Peripheral Sensitization ◽  
Primary Sensory Neurons ◽  
Transient Receptor ◽  
Underlying Mechanisms

Neuropathic pain is mainly triggered after nerve injury and associated with plasticity of the nociceptive pathway in primary sensory neurons. Currently, the treatment remains a challenge. In order to identify specific therapeutic targets, it is necessary to clarify the underlying mechanisms of neuropathic pain. It is well established that primary sensory neuron sensitization (peripheral sensitization) is one of the main components of neuropathic pain. Calcium channels act as key mediators in peripheral sensitization. As the target of gabapentin, the calcium channel subunit α2δ1 (Cavα2δ1) is a potential entry point in neuropathic pain research. Numerous studies have demonstrated that the upstream and downstream targets of Cavα2δ1 of the peripheral primary neurons, including thrombospondins, N-methyl-D-aspartate receptors, transient receptor potential ankyrin 1 (TRPA1), transient receptor potential vanilloid family 1 (TRPV1), and protein kinase C (PKC), are involved in neuropathic pain. Thus, we reviewed and discussed the role of Cavα2δ1 and the associated signaling axis in neuropathic pain conditions.

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