Intracerebroventricular Treatment with Resiniferatoxin for TRPV1 Desensitization in the Mouse Brain

Take a microsyringe filled with resiniferatoxin, a high-affinity agonist of TRPV1 receptors, pain-sensitive ion channels expressed on sensory neurons.

Pass the needle through a metal tube, exposing a short end of the tip for precise ventricular targeting.

Position an anesthetized mouse prone and disinfect its head using alcohol. Hold the head firmly to stabilize the skull.

Move the needle laterally on the scalp until it hooks onto the sagittal suture.

Shift the needle to the right, then move rostrally to hook onto the coronal suture.

Insert the needle into the right lateral ventricle, then inject the RTX slowly.

Hold the needle briefly to allow RTX diffusion, then withdraw it slowly to prevent backflow.

RTX binds to TRPV1 channels on sensory neurons in the brain, causing sustained calcium influx and prolonged neuronal depolarization.

This triggers phosphorylation-mediated TRPV1 desensitization, followed by TRPV1 internalization and lysosomal degradation, which reduces neuronal responsiveness to pain stimuli.

Anesthetize a mouse with pentobarbital sodium intraperitoneally and check for loss of righting reflex. For subcutaneous treatment, inject RTX at 20 micrograms per milliliter into the b