• Modeling Mechanism：

  Capsaicin, as a TRPV1-specific agonist, induces Ca²⁺ influx upon activation. This influx occurs through both the Ca²⁺/calpain pathway and the axonal microtubule depolymerization (increasing the content of free tubulin), jointly mediating TRPV1⁺ nociceptive nerve ending ablation. Nerve ending ablation reduces the transmission of abnormal pain signals, thereby alleviating mechanohypnosis. Moreover, this process is independent of TRPV1 S801 site phosphorylation.

• Related Products：

  Capsaicin (T1062)

• Modeling Method：

  Experimental Subject：

  Mice: C57BL/6J, TRPV1^Cre transgenic mice, ROSA^mT/mG transgenic mice, homozygous Calca^Cre mice, TRPV1 S801A knock-in mice, littermate wild-type (WT) mice (as controls); adult (22–30 g)

  Dosage and Administration Route：

  Pain model establishment: ION-CCI surgery (bilateral suborbital nerves ligated with 4.0 chromium sutures, 2 ligatures spaced 2 mm apart), resulting in stable mechanical hyperalgesia 14 days post-surgery;
  Capsaicin administration: 10 μg/20 μL capsaicin (dissolved in 25% PEG300+75% water) administered via subcutaneous injection into facial skin

  Dosing Frequency and Duration Model：

  Single injection of capsaicin 14 days post-ION-CCI surgery

• Validation：

  Behavioral studies: 3-7 days after capsaicin injection, the mechanical pain threshold in the face of ION-CCI mice was significantly increased, and mechanical hyperalgesia was relieved; Molecular markers: Increased content of free tubulin in DRG neurons; Histology: Decreased density of TRPV1⁺ nerve endings and CGRP⁺ peptidergic nerve endings in facial and hind paw skin (ablation effect); Functional validation: Calcium imaging showed that capsaicin could induce Ca²⁺ influx in DRG neurons.

*Precautions： To facilitate the testing, a blind method was used. Mice were acclimatized for 20 minutes daily for 3 days prior to the experiment to reduce stress interference. After the experiment, mice were sacrificed, and DRG and facial/hind paw skin tissue were collected for immunohistochemistry, Western blot, or free microtubule detection.

*References：Arora V,et,al. Capsaicin-induced depolymerization of axonal microtubules mediates analgesia for trigeminal neuropathic pain. Pain. 2022 Aug 1;163(8):1479-1488.

• Modeling Mechanism：

  Capsaicin's target TRPV1 channel is upregulated under acetone-ether-water (AEW) induction due to skin barrier disruption: TRPV1⁺ sensory neurons proliferate in the trigeminal ganglion (TG), and the density of TRPV1⁺ sensory fibers innervating the skin increases; after enhanced TRPV1 sensitivity, capsaicin no longer induces pain-related rubbing behavior, but instead triggers itch-related scratching behavior. The core mechanism is the activation of the peripheral TRPV1 pathway and sensitization of the central itch signaling pathway.

• Related Products：

  Capsaicin (T1062)

• Modeling Method：

  Experimental Subject：

  Mice: C57BL/6 (expressing Pirt-GCaMP3 and TRPV1-PLAP transgenes) • Male • 8–10 weeks old

  Dosage and Administration Route：

  First shave the facial hair of the mouse, then perform AEW treatment (apply acetone-di-ethyl ether 1:1 mixture for 20 seconds, followed by distilled water for 30 seconds); after modelling, administer a subcutaneous injection of 500 nM capsaicin

  Dosing Frequency and Duration Model：

  AEW twice daily for 4–8 consecutive days; Capsaicin administered as a single subcutaneous injection

• Validation：

  Capsaicin-induced AEW treatment mice showed significant scratching behavior (54.00±4.86 times), a substantial increase compared to the control group (5.25±1.44 times), while pain-related wiping behavior showed no significant change. Molecular markers: TRPV1 mRNA and protein expression were upregulated in TG, and the proportion of TRPV1⁺ neurons in the V3 branch increased (20.2% in the control group vs. 30.2% on day 4 of AEW). Histologically: The density of TRPV1⁺ sensory fiber innervation in the skin increased by 35.89%. Functional validation: Calcium imaging showed that the response rate of Capsaicin (50 nM, 500 nM, 1-10 μM) to TG neurons was significantly higher than that in the control group.

*Precautions： Behavioral tests were conducted 4-8 days after modeling (observing scratching/wiping behavior for 30-60 minutes). Mice were euthanized after the tests to collect TG and skin tissue. The experimental environment was maintained at 20-24℃ and 45%-65% humidity. Behavioral assessments were performed by blinded observers.

*References：Yu G,et,al. Enhanced itch elicited by capsaicin in a chronic itch model. Mol Pain. 2016 Apr 26;12:1744806916645349.