Fig. 5.  There are differences in the percentages of tropomyosin-related kinase A receptor (TrkA)-positive sensory nerve fibers that innervate the bone versus  skin. The skin is innervated by thickly myelinated A-β fibers (TrkA-negative), thinly myelinated Aδ fibers (both TkA-negative and TrkA-positive), unmyelinated peptide-rich C fibers (TrkA-positive), and unmyelinated peptide-poor C-fibers (TrkA-negative). In contrast, the bone appears to be predominantly innervated by thinly myelinated Aδ fibers (mostly TrkA-positive) and peptide-rich C-fibers (also mostly TrkA-positive). The percentages and types of sensory nerve fibers innervating the skin51,54,148,149and bone52,123,150,151were estimated from previous studies. Thus overall more than 80% of all sensory nerve fibers that innervate the bone are TrkA-positive, whereas only 30% of the sensory nerve fibers that innervate skin are TrkA-positive, which might help explain why blocking nerve growth factor or TrkA is highly efficacious in attenuating skeletal pain. Reproduced with modifications from Castaneda-Corral G, Jimenez-Andrade JM, Bloom AP, Taylor RN, Mantyh WG, Kaczmarska MJ, Ghilardi JR, Mantyh PW: The majority of myelinated and unmyelinated sensory nerve fibers that innervate bone express the tropomyosin receptor kinase A. Neuroscience 2011; 178:196–207, with permission from Elsevier Ltd.123