RhyothemisJan 9, 2024

Animalogic put out an interesting Floralogic episode on the extreme, long-lasting pain caused by gympie gympie - a plant in the same family as stinging nettle -

Gympie Gympie Is Doing Everything It Can To Ruin Your Life
https://youtu.be/kIGQYE8pH_Y?si=4QN-DzBHdRg3OEen

It's an Australian plant, of course.

"Altering the activation threshold, combined with effects upon inactivation, likely leads to nociceptor activation and the sensation of pain, akin to biophysical changes observed in painful conditions associated with NaV1.7 [SCN9A] gain-of-function mutations such as inherited erythromelalgia (IEM) and paroxysmal extreme pain disorder (PEPD), respectively ... As the gympietides bear little similarity to any other known NaV modulators and display unusual effects particularly on NaV inactivation, it is difficult to predict possible binding sites at this point. However, based on activity of animal venom–derived toxins and the biophysics of NaV gating, the extracellular loops of the domain IV voltage sensor could be a possible binding site."
https://doi.org/10.1126/sciadv.abb8828

#Pain #nociception #NaturalProducts #erythromelalgia #gympietides #SodiumChannels #SCN9A

Gympie Gympie Is Doing Everything It Can To Ruin Your Life

YouTube
Show threadRhyothemisJan 9, 2024

Based on the suggested mechanism of action⬆️ , an erythromelalgia case study* and my own experience with chronic pain and erythromelalgia, for longer-term management of gympie gympie exposure I would suggest oral low dose naltrexone and - maybe - topical magnesium chloride solution (aka 'magnesium oil'), after other treatment methods (e.g., waxing) have been tried.

*
Erythromelalgia in a Patient with Mast Cell Activation Syndrome: Response to Low Dose Naltrexone
https://doi.org/10.25251/skin.4.3.15

SKIN The Journal of Cutaneous Medicine

Erythromelalgia is a rare condition that may be associated with a variety of underlying conditions and can be refractory to therapy. We report a case of a patient with mast cell activation syndrome (MCAS) who developed erythromelalgia and responded to low dose naltrexone (LDN).

Show threadRhyothemis

on my to-read list:

Pain-causing stinging nettle toxins target TMEM233 to modulate NaV1.7 function
https://doi.org/10.1038/s41467-023-37963-2

#Pain #gympietides #nociception #SodiumChannels #TMEMchannels #NaturalProducts

Jan 9, 2024 at 5:39pmWeb
Show threadRhyothemisJan 10, 2024

from ⬆️ "These nettles are renowned for inflicting extremely painful stings that are characterized by acute electric shocklike, piercing, pricking and burning sensations lasting for many hours, followed by intermittent painful flares and allodynia that persists for days or even weeks."

Similarities to other types of neuropathic pain, including small fiber neuropathy and Long Covid associated neuropathy.

~

"These results provide important insights into the function of NaV channels in sensory neurons, identify TMEM233 as a previously unknown NaV1.7interacting protein, and describe the dispanins as bifunctional proteins that cause allosteric changes in channel gating upon binding of pain causing venom peptides."

~

Not finding much on TMEM233. Some dispanins are interferon activated.

review article from 2012:
- The Dispanins: A Novel Gene Family of Ancient Origin That Contains 14 Human Members
https://doi.org/10.1371%2Fjournal.pone.0031961

"The IFITM1–3 proteins were identified 25 years ago as being upregulated by interferons (IFN) [6]. Recently they received considerable attentions as IFITM1–3 were found to prevent infection of a growing list of viruses such as HIV-1, SARS influenza A H1N1, West Nile and Dengue fever viruses [7], [8], [9], [10]. Hence, proteins of the IFITM family mediate part of the antiviral response orchestrated by IFNs. However, the IFITM family is also involved in other processes such as oncogenesis, bone mineralization (IFITM5) and germ cell development (IFITM1 and 3) and IFITM5 has not been identified as interferon-inducible [11], [12], [13], [14]. Although the biological roles of the IFITM genes are emerging, no thorough evolutionary analysis has been performed on this group.

In this study, we sought to infer the evolutionary history of the human IFITM genes and identify potential homologues. We mined 36 eukaryotic species, covering all major eukaryotic groups, and found that the IFITMs form a subfamily in a larger novel family that has ten human members in addition to the four IFITM genes. We propose Dispanins as a novel name for this family, which refers to their common 2TM structure. "

#TMEM233 #dispanins #IFITM #interferon #Pain #neuropathy

The Dispanins: A Novel Gene Family of Ancient Origin That Contains 14 Human Members

The Interferon induced transmembrane proteins (IFITM) are a family of transmembrane proteins that is known to inhibit cell invasion of viruses such as HIV-1 and influenza. We show that the IFITM genes are a subfamily in a larger family of transmembrane (TM) proteins that we call Dispanins, which refers to a common 2TM structure. We mined the Dispanins in 36 eukaryotic species, covering all major eukaryotic groups, and investigated their evolutionary history using Bayesian and maximum likelihood approaches to infer a phylogenetic tree. We identified ten human genes that together with the known IFITM genes form the Dispanin family. We show that the Dispanins first emerged in eukaryotes in a common ancestor of choanoflagellates and metazoa, and that the family later expanded in vertebrates where it forms four subfamilies (A–D). Interestingly, we also find that the family is found in several different phyla of bacteria and propose that it was horizontally transferred to eukaryotes from bacteria in the common ancestor of choanoflagellates and metazoa. The bacterial and eukaryotic sequences have a considerably conserved protein structure. In conclusion, we introduce a novel family, the Dispanins, together with a nomenclature based on the evolutionary origin.