Mapping Genicular Nerve Endings for Optimal Pain Management: A Comparative Cadaveric Analysis Between Native Versus Prosthetic Knee

Pain Med. 2026 Sep 28:pnag130. doi: 10.1093/pm/pnag130. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic knee pain, often due to osteoarthritis (OA), is frequently treated with genicular nerve blocks, radiofrequency ablation (RFA) or genicular artery embolization (GAE). However, the intracapsular distribution of nerve endings and vascular networks key pain parameters remains poorly defined in native and prosthetic knees.

QUESTIONS/PURPOSES: We compared the distribution of intracapsular nerve endings and vascular density in native versus prosthetic knee capsules across five genicular nerve targets in relation to knee pain.

METHODS: Ten native and ten prosthetic cadaveric knees were analyzed. Capsular samples (20 × 5 mm) were harvested from regions innervated by the superior medial, superior lateral, and inferior genicular nerves, the recurrent fibular nerve, and the infrapatellar branch of the saphenous nerve. Nerve endings and vascular densities were quantified after histologic and immunohistochemical analysis comparatively.

RESULTS: Native knees had higher free nerve ending (FNE) density (p < 0.001), while prosthetic knees showed greater vascular density (p = 0.001) and increased Pacini (p = 0.006), Golgi (p = 0.01), and unclassified endings (p = 0.019). Correlation between FNE and vascular density was modest in native knees (r = 0.41) and negligible in prosthetic knees (r = 0.09). Patterns were consistent across all nerve targets. All five nerve targets showed no difference in their mechanoreceptor and vascular density distribution.

CONCLUSION: Dense FNE populations in native knees support genicular nerve-targeted interventions for OA pain. The increased vascularity and mechanoreceptor innervation identified in prosthetic knees suggest that inflammatory, angiogenic, and sensory mechanisms may contribute to persistent post-surgical pain. Whether interventions targeting these pathways, such as radiofrequency ablation or genicular artery embolization, provide better clinical benefit together remains to be established.

PMID:42803442 | DOI:10.1093/pm/pnag130