Background: Chemotherapy-induced peripheral neuropathy (CIPN) remains a major clinical challenge because effective mechanism-based therapies are limited. Wrist-ankle acupuncture (WAA) has shown analgesic benefits in CIPN, but the spinal mechanisms underlying its effects remain largely unclear. Methods: Mechanical allodynia and thermal hyperalgesia were evaluated in a paclitaxel-induced CIPN mouse model. The cellular distribution of the α 7 nicotinic acetylcholine receptor (α 7nAChR) in the spinal dorsal horn was examined by immunofluorescence co-staining with NeuN-positive neurons. Spinal dorsal horn glutamate content and glutamatergic/N-methyl-D-aspartate receptor (NMDAR)-related signaling readouts (NMDAR NR2B subunit NR2B, vesicular glutamate transporter 2 VGluT2, phosphorylated c-Jun N-terminal kinase p-JNK, phosphorylated cAMP response element-binding protein p-CREB, and calcitonin gene-related peptide CGRP) were quantified using biochemical assays and Western blotting. To interrogate mechanism, an NMDAR agonist was administered intrathecally in a subset of mice prior to WAA. In parallel, neuronal α 7nAChR was conditionally ablated via Cre–LoxP gene editing by delivering rAAV-hSyn-Cre into the lumbar dorsal horn of Chrna7flox/flox mice and by generating VGluT2 neuron–specific Chrna7 conditional knockout mice ( Chrna7flox/flox; Slc17a6 -Cre + ). Results: WAA significantly attenuated mechanical allodynia and thermal hyperalgesia in CIPN mice. These behavioral improvements were accompanied by reduced dorsal horn glutamate levels and decreased NR2B/VGluT2-related measures and downstream markers (p-JNK, p-CREB, and CGRP), consistent with dampened glutamatergic/NMDAR pathway activity. Notably, intrathecal NMDAR activation or conditional loss of α 7nAChR markedly blunted both the analgesic effect of WAA and its associated spinal molecular changes. Conclusion: WAA alleviates paclitaxel-induced neuropathic pain in an α 7nAChR-dependent manner, at least in part through modulation of spinal glutamatergic/NMDAR-related signaling. Keywords: wrist-ankle acupuncture, chemotherapy-induced neuropathic pain, α 7nAChR, spinal dorsal horn, glutamatergic/NMDAR-related signaling
Lan et al. (Mon,) studied this question.