## 4 Discussion  
In this study, increased expression of pain-related factors was found in pathologic LHBTs, and these expressions also showed an increase in the adjacent structures, including the anterior capsule and rotator interval, in patients with full-thickness rotator cuff tears. These results indicated that a pathologic LHBT acts as a pain generator itself, and adjacent structures reacted differently depending on the status of the LHBT. The analyzed markers are neuronal peptides involved in different aspects of the pain-generating mechanism, and their appearances have been confirmed in various tendon and joint diseases [4; 13; 14; 15; 16]. The abnormal increase in neural and pain-related markers demonstrated the presence of pathological neural changes in various tendon diseases [17; 18]. PGP 9.5 is a general neuronal marker that represents the presence of general nerve fibers [19; 20]. GAP43 is a neuronal membrane protein involved in axonal growth and regeneration that represents a marker for nerve growth [19; 21]. The neuropeptide CGRP is widely distributed in nociceptive pathways in both the central and peripheral nervous systems and is involved with the sensation of joint pain [14; 22]. CD34 is an endothelial cell marker and CD34-positive vessels are related to increased fibroblast cellularity in tendons under pathologic conditions [13]. Substance P is a neuropeptide acting as both a neurotransmitter and a neuromodulator and is released from the terminals of specific sensory nerves. Painful tendons showed an increased presence of substance P-containing nerves, and neural sprouting of substance P fibers accompanies vascular hyperplasia [23]. P75 is a nerve growth factor receptor that is expressed in nerve fibers around blood vessels. It also showed increased expression in the capsules of patients with frozen shoulder [16]. Finally, the expression of the S100 protein is significantly altered in various neurodegenerative diseases, inflammation, and autoimmune diseases [24; 25; 26; 27]. In the case of the LHBT under pathologic conditions (group 2), the expressions of PGP9.5, GAP43, CGRP, and CD34 were significantly higher than in group 1 with the normal LHBTs. CGRP-positive nerve fibers are significantly increased in chronic tendonopathy with confirmation of CGRP expression in both unmyelinated and myelinated axons of the LHBT [28]. Along with CGRP, PGP9.5 was detected in nerve fibers of the human patellar tendon in the vicinity of some of the blood vessels and in thin nerve fascicles [29]. In fact, increased expression of pain-related factors is highly predictable, as the LHBT under pathologic conditions is a well-known pain generator that coexists with rotator cuff tears. However, one marker that showed no significance among the analyzed factors in any obtained tissues was substance P. Considering the finding of no significant difference in the expression of substance P between normal cadaveric samples and pathologic LHBTs in a previous study by [PERSON] et al [30], the reactivity of substance P in the etiology of LHBT pathology can be relatively weak compared to other factors. The anterior capsule and rotator interval also contribute to the generation of shoulder pain in various ways. In particular, with the clinical manifestation of joint stiffness in rotator cuff tear patients, factors associated with inflammation or fibrosis have shown upregulation in capsules and rotator interval tissues [31]. In a similar fashion, the expression of the evaluated factors was consistently upregulated with abnormality of the LHBT. Previously, the pathologic connection between the LHBT and the shoulder capsule was revealed by [PERSON] et al., which explained the insertion of relatively large nerve fibers from the capsule to the central portion of the LHBT [32]. Similar to the reaction shown with the LHBT, the response shown for substance P was lukewarm compared to other factors.