SU-Eohyeol Pharmacopuncture Ameliorates Parkinson's Disease-Associated Pain via the CB1 and PPARγ Pathways in an MPTP-Induced Mouse Model.

Pain is a ubiquitous nonmotor symptom in Parkinson's disease (PD), substantially impairing quality of life. Although pharmacological and surgical interventions provide partial relief, effective treatment for PD-associated pain remains limited. Pharmacopuncture, an injection of herbal extracts into acupoints, has demonstrated potential in pain management. This study evaluated the analgesic and neuroprotective effects of SU-Eohyeol pharmacopuncture (SUEHP) in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. C57BL/6N male mice received repeated intraperitoneal injections of MPTP to induce PD-related pain. SUEHP was bilaterally administered at the GB34 acupoint or a control site. Pain sensitivity and motor function were evaluated, followed by postsacrifice histological assessments. Administration of SUEHP at GB34 significantly attenuated MPTP-induced mechanical hypersensitivity and spinal c-Fos expression, enhanced tyrosine hydroxylase and brain-derived neurotrophic factor expression in the substantia nigra, and partially restored motor function. However, cotreatment with a CB1 or PPARγ antagonist eliminated these analgesic and neuroprotective effects, suggesting that SUEHP mediates its effects through specific pathways. Transcriptomic profiling of the midbrain and spinal cord revealed that SUEHP modulated inflammation, dopaminergic neurogenesis, and synaptic signaling pathways, which were typically reversed using cotreatment with CB1 or PPARγ antagonist. Collectively, SUEHP alleviates PD-associated pain and neurodegeneration through CB1 and PPARγ pathways, suggesting its potential as a safe, noninvasive complementary therapy for PD symptom management.