Dorsal root ganglion neurons with dichotomizing axons projecting to the hip joint and the knee skin in rats: possible mechanism of referred knee pain in hip joint disease

Patients who have hip joint diseases sometimes complain of knee pain as well as hip joint area pain. However, the precise sensory innervation pattern and correlation of the sensory nerves of the hip joint and knee are unknown. The purpose of this study was to investigate dorsal root ganglion (DRG) neurons with dichotomizing axons projecting to both the hip joint and the knee skin in rats using double fluorescent labeling techniques, and to examine characteristics of the DRG neurons with dichotomizing axons using immunohistochemical staining for inflammatory neuropeptides such as calcitonin gene-related peptide (CGRP). For 20 rats, two kinds of neurotracers, Fluoro-Gold (FG) and 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI), were used in the double-labeling study. FG was injected into the left hip joint, and DiI was applied to the left medial portion of knee skin. Ten days after application, bilateral DRGs were harvested and immunohistochemically stained for CGRP. DRG neurons double labeled with FG and DiI were observed only from L2 to L4 on the left side. Approximately 1.6% of all DRG neurons innervating the hip joints had other axons that extended to the medial portion of knee skin, and 35% of double-labeled neurons were CGRP positive. Our results showed that the double-labeled neurons had peripheral axons that dichotomized into both the hip joint and the knee skin. CGRP-positive neurons of these dichotomizing fibers may play some role in the manifestation of referred knee pain with hip joint pain.