Human Placental Extract as a Promising Epidural Therapy for Lumbar Spinal Stenosis: Enhancing Axonal Plasticity and Mitigating Pain and Inflammation in a Rat Model.

BACKGROUND: Epidural injections treat lumbar spinal stenosis (LSS) by targeting localized inflammation and tissue damage. However, current medications such as corticosteroids and local anesthetics often have limited efficacy and significant adverse effects. METHODS: Human placental extract (HPE), with regenerative and anti-inflammatory properties, was tested for its axon-promoting and pain-relieving effects in an in vitro model using dorsal root ganglion neurons exposed to hydrogen peroxide (H(2)O(2)). RESULTS: Various HPE doses were applied, and 2.5 or 5 mg/mL enhanced cell viability and neurite outgrowth while alleviating the increased expression of pain-related markers (IB4, CGRP, TRPV1) caused by H(2)O(2) in a dose-dependent manner. Subsequently, rats with LSS received epidural injections of 10 or 20 mg/kg HPE five times weekly for four weeks. In vivo results showed that repeated HPE injections significantly reduced ED1(+) macrophages and altered the expression of M1 (iNOS, TNF-α, COX-2) and M2 (Arg1, CD206) macrophage markers. Pain-related markers (TRPV1, IB4, CGRP, NF200) and genes (Il1rn, Scn9a) were significantly downregulated in 3D dorsal root ganglion tissues. Additionally, the 3D spinal cord exhibited increased serotonergic axons and upregulated expression of genes related to axonal growth and neurotrophic factors (Nefh, Ngf, Bdnf, Gap43). CONCLUSIONS: Our findings suggest that repeated epidural injections of human placental extract in LSS rats can improve locomotor function. This underscores the potential benefits of human placental extract as an epidural agent, enhancing the recovery process and offering a new and minimally invasive treatment strategy for LSS.