Scholarlink

<p> Allodynia to mechanical stimuli is one of the most prevalent symptoms in paclitaxel-treated cancer patients. Paclitaxel induces ATP release from nerve terminals; thus, peripheral primary sensory neurons can be sensitized by ATP, as a large subgroup expresses purinergic P2X<sub>2/3</sub> and P2X<sub>3</sub> receptors. In this study, we examined the role of P2X<sub>2/3</sub> and P2X<sub>3</sub> receptors in paclitaxel-treated rats with&#xa0;allodynia. We assessed the paw withdrawal threshold as an allodynia test on paclitaxel-treated rats and evaluated the intrathecal and systemic effects of purinergic receptor antagonists and the transient knockdown of P2X<sub>3</sub> receptor expression in male and female allodynic rats. A single dose of paclitaxel decreased the paw withdrawal threshold to mechanical stimulation in both sexes. Pharmacological blockade of spinal P2X<sub>3</sub> and P2X<sub>2/3</sub> receptors with Ro-51, TNP-ATP, and systemic suramin reversed allodynia in paclitaxel-treated rats. In addition, the transient knockdown of P2X<sub>3</sub> receptors with intrathecal siRNA administration had an antiallodynic effect that lasted until 72&#xa0;h post-transfection. Paclitaxel produced an increase in the P2X<sub>3</sub> receptor expression in dorsal root ganglia but not in dorsal horn spinal cord. In conclusion, spinal P2X<sub>2/3</sub> and P2X<sub>3</sub> receptors have a significant role in allodynia to mechanical stimulation in paclitaxel-treated rats, regardless of sex. Therefore, the blockade of these receptors could be an alternative pharmacological target for alleviating sensory symptoms of paclitaxel-induced peripheral neuropathy in patients with cancer.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Spinal P2X3 receptors blockade reverses paclitaxel-induced allodynia in rats

  • 期刊论文

  • 发表日期：

    2026年1月21日

查看全文
  • Pedro Segura-Chama,
  • Lucio Antonio Ramos-Chávez,
  • Nashiely Yañez-Recendis,
  • Francisco Pellicer,
  • Martha León-Olea,
  • Angélica Almanza,
  • Francisco Mercado

摘要

Allodynia to mechanical stimuli is one of the most prevalent symptoms in paclitaxel-treated cancer patients. Paclitaxel induces ATP release from nerve terminals; thus, peripheral primary sensory neurons can be sensitized by ATP, as a large subgroup expresses purinergic P2X2/3 and P2X3 receptors. In this study, we examined the role of P2X2/3 and P2X3 receptors in paclitaxel-treated rats with allodynia. We assessed the paw withdrawal threshold as an allodynia test on paclitaxel-treated rats and evaluated the intrathecal and systemic effects of purinergic receptor antagonists and the transient knockdown of P2X3 receptor expression in male and female allodynic rats. A single dose of paclitaxel decreased the paw withdrawal threshold to mechanical stimulation in both sexes. Pharmacological blockade of spinal P2X3 and P2X2/3 receptors with Ro-51, TNP-ATP, and systemic suramin reversed allodynia in paclitaxel-treated rats. In addition, the transient knockdown of P2X3 receptors with intrathecal siRNA administration had an antiallodynic effect that lasted until 72 h post-transfection. Paclitaxel produced an increase in the P2X3 receptor expression in dorsal root ganglia but not in dorsal horn spinal cord. In conclusion, spinal P2X2/3 and P2X3 receptors have a significant role in allodynia to mechanical stimulation in paclitaxel-treated rats, regardless of sex. Therefore, the blockade of these receptors could be an alternative pharmacological target for alleviating sensory symptoms of paclitaxel-induced peripheral neuropathy in patients with cancer.