Selective Ablation of Nociceptive Neurons to Eliminate Hyperalgesia and Neurogenic Inflammation

[StoneInFocus]

This is an old article but still very interesting.

I would not know if injecting Resiniferatoxin (RTX) into the inner ear would also destroy other cells besides type II afferents,

But if there was some sort of receptor uniquely expressed on type II afferents and a toxin that could selectively destroy cells with that receptor, maybe it could be a treatment option for tinnitus and especially noxacusis, if type II afferents are indeed the culprit.

Object: Neuropathic pain is mediated by nociceptive neurons that selectively express the vanilloid receptor 1 (VR1). Resiniferatoxin (RTX) is an excitotoxic VR1 agonist that causes destruction of VR1-positive neurons. To determine whether RTX can be used to ablate VR1-positive neurons selectively and to eliminate hyperalgesia and neurogenic inflammation without affecting tactile sensation and motor function, the authors infused it unilaterally into the trigeminal ganglia in Rhesus monkeys.

Methods: Either RTX (three animals) or vehicle (one animal) was directly infused (20 microl) into the right trigeminal ganglion in Rhesus monkeys. Animals were tested postoperatively at 1, 4, and 7 weeks thereafter for touch and pain perception in the trigeminal distribution (application of saline and capsaicin to the cornea). The number of eye blinks, eye wipes, and duration of squinting were recorded. Neurogenic inflammation was tested using capsaicin cream. Animals were killed 4 (one monkey) and 12 (three monkeys) weeks postinfusion. Histological and immunohistochemical analyses were performed. Throughout the duration of the study, response to high-intensity pain stimulation (capsaicin) was selectively and significantly reduced (p < 0.001, RTX-treated compared with vehicle-treated eye [mean +/- standard deviation]): blinks, 25.7 +/- 4.4 compared with 106.6 +/- 20.8; eye wipes, 1.4 +/- 0.8 compared with 19.3 +/- 2.5; and squinting, 1.4 +/- 0.6 seconds compared with 11.4 +/- 1.6 seconds. Normal response to sensation was maintained. Animals showed no neurological deficit or sign of toxicity. Neurogenic inflammation was blocked on the RTX-treated side. Immunohistochemical analysis of the RTX-treated ganglia showed selective elimination of VR1-positive neurons.

Conclusions: Nociceptive neurons can be selectively ablated by intraganglionic RTX infusion, resulting in the elimination of high-intensity pain perception and neurogenic inflammation while maintaining normal sensation and motor function. Analysis of these findings indicated that intraganglionic RTX infusion may provide a new treatment for pain syndromes such as trigeminal neuralgia as well as others.

→ Selective ablation of nociceptive neurons for elimination of hyperalgesia and neurogenic inflammation

 

[StoneInFocus]

Here's an article from 2023 which mentions that RTX can also be used to desensitize neurons instead of ablating them:

Per definition, desensitization by RTX is reversible. However, RTX can also kill sensory neurons, an irreversible effect. The toxic action of RTX is thought to be due to a combination of Ca2+ overload and osmotic injury. As we will see below, both reversible desensitization and permanent ablation of sensory neurons can be exploited for therapeutic purposes, most notably for pain control. Of note, desensitization to RTX may last for several months and is repeatable by a second RTX administration.

There are currently clinical trials going on for bladder pain, cancer pain, and knee osteoarthritis.