Expression of TrkA and GFRα1, and their coexpression in muscle innervating primary afferent neurons in rats

On the way of analyzing the mechanism of delayed onset muscle soreness, author’s group found that nerve growth factor (NGF) and glial cell line derived neurotrophic factor (GDNF) synergistically interact to induce muscular mechanical hyperalgesia. However, it is believed that NGF and GDNF work on different sets of DRG neurons that express NGF receptor, TrkA or GDNF receptor, GFR α 1–RET. However, this result was obtained from skin–innervating neurons or whole DRG neurons. It is not known whether muscle innervating DRGs are similar. In this experiment we examined whether it is also true for muscle innervating DRG neurons. We identified muscle innervating DRG neurons using retrograde tracing with Fluoro–Gold. Under anesthesia FG (4%, 10 μl) was injected to 10 points each of medial and lateral head of gastrocnemius muscle (GC). Ten to eleven days later rats were perfused and fixed under deep anesthesia. Using serial sections immunohistochemistry for FG and double in situ hybridization for TrkA and GFR α 1 were performed. As a result 39%–50% of FG+ DRG neurons were TrkA+, and 69–77% were GFR α 1+. Co–expression of TrkA and GFR α 1 was observed in 24%–29% DRG neurons innervating GC. The size distribution of FG + DRG neurons did not show a skewness in small size range (< 600 μm 2 ), rather distributed equally in small to large cell ranges. Size distribution of TrkA+ neurons and double positive (TrkA+ and GFR α 1+) also showed no skewness in small size range and distributed widely from small to large size. A part of these TrkA+ ⁄ GFR α 1+ coexpressing neurons might be the site of synergistic interaction of NGF and GDNF.