*4.4. How Are the Shoulder and the Psyche Connected?*

The upper limb is especially characterized by dexterity, motion, and sensibility, all of which are at stake when the shoulder is functionally disabled and painful [65]. Mitchell et al. [66] suggest upper-limb injuries to compromise the function of the limb and, along with that, also to hamper psychosocial well-being. Surprisingly, however, as these authors further report, long-term outcomes are similar for those treated with amputation or limb salvage. Other authors find only a weak correlation and conclude there is no such thing as a "frozen shoulder personality" [31]. Notwithstanding, the comorbid conditions of diabetes and arterial hypertension are both linked to personality on genetic [67], clinical [68,69], and therapeutic [70] levels. Thus, the frequent coincidence of shoulder impingement, diabetes mellitus, and arterial hypertension may be rooted at least partly in shared psychosocial factors, which possibly promote their common manifestation [71]. For example, neuroticism is associated with higher levels of hypochondriasis, and may affect dietary habits and other aspects of illness behavior [72]. Generally, patients with the comorbidity of mental disorders and painful physical symptoms display higher levels of emotional distress, poorer physical functioning, and lower rates of help seeking [73].

As to the mechanisms linking psychiatric symptoms and shoulder pain, the elements of the fear avoidance model, precisely fear avoidance beliefs such as kinesiophobia and pain catastrophizing, are likely involved in the dynamics of the chronification of shoulder pain. Accordingly, there [30] was a relationship between emotional distress, depression, anxiety, preoperative concerns, and fear avoidance as well as chronic shoulder pain. However, these authors highlight the weakness of this association, as well as the presence of several biases. Moreover, the more widespread the pain, the more robust the association with psychological variables, leading the authors to conclude that generalized pain involving the shoulder is more bio-psycho-social than pain restricted to the shoulder only. Likewise, Sarquis et al. [74] found shoulder pain to be most disabling when embedded in a state of generalized pain, involving other sites as well. In line with this theorizing, knee pain especially predicts the spreading of pain [48]. For the sake of the full picture, it seems noteworthy that traditional and complementary methods (e.g., acupuncture) play only a minor role in the treatment of shoulder pain. Notwithstanding, integrative approaches are potentially promising as they effectively mitigate pain and improve states of negative affectivity, as well [75].

#### *4.5. Comorbidity*

Due to its complex anatomy, which involves not only the rotator cuff, but also capsuloligamentous structures as well as their chronic inflammation, fibrosis, and contracture, the shoulder unfolds a complicated and multifaceted etiopathology of its chronic affection with pain. Aspects of lifestyle, increasing load, immunological factors, as well as psychological features, not to mention hormonal and possibly genetic factors, all adjust the risk of SIS [76,77], and the profile of comorbidities of shoulder pain may serve to illustrate this stance. As regards the physical comorbidities, they apparently share some of the associative patterns between psychological factors and physical disease. Depression, anxiety, and neuroticism are overrepresented not only in those with shoulder pain, but also in those with arterial hypertension and diabetes [78].

One should nevertheless bear in mind that, while certain labilizing traits may have beneficial effects on one disorder, they may still be a deteriorating factor in another one [79,80].

Exemplifying this statement, neuroticism may confer a greater potential of healthrelated anxiety, promoting a healthier lifestyle and greater levels of adhesion with respect to cardiovascular disease [81]. Contrarily, neuroticism is not considered protective, but a vulnerability factor, when it comes to arthritis-related pain [82].

#### *4.6. The Shoulder and the Knee: Key to Bipedalism*

The knee is of even more importance and relevance for chronic pain than the shoulder. Reasons for the knee to bear complications include reduced participation, walking distance, and speed [83]. Yet, even more importantly, the knee is well-nigh key to bipedalism. The shoulder mirrors these qualities as it is also a peculiar joint with specific anatomy and function, is linked to chronic pain, and, once disordered, threatens the individual participation fundamentally. Both joints are essential underpinnings of the human twolegged mobility and our upright gait, and hence their pathologies have the potential of seriously crippling the body's functional capabilities. This argument may help understand the psychological impact of those entities on general well-being. In addition, both entities are embedded in a pattern of physical morbidity that adds to the individual's burden, hampering adaptive coping even more.

Not least [57], coping represents a competency depending on the individual's psychic presentation, not only as far as mood disorders are concerned, but also with respect to the fundamental organization of the psyche as reflected in the individual's personality. Thus, there may be a complex interaction between these dispositions and shoulder pain.

#### *4.7. A Note on Centralized Pain and the Lateralized Nature of Pain and Its Psychosocial Correlates*

In the nineteenth century, English physician John Spender elaborated a new classification of the initial symptoms of OA including changes in velocity and tension of the heart's action, vasomotor changes, and specific neural symptoms [83]. The suggestion implied by this description was that the CNS could be functionally involved in the pathogenesis of OA. Contemporarily, this theory is revived insofar as there is the proposal of low-grade infection regulated top-down by a setpoint, as Morris et al. [84] state, that adjusts the neural, hormonal, inflammatory, and immune tone. The synovium and other joint structures are innervated by sympathetic and sensory fibers projecting to the thalamus and diencephalon. The higher the autonomic tone, the fewer anti-inflammatory effects of the parasympathicus are being brought to bear [84]. On the contrary, total knee arthroplasty is apparently associated with increased levels of circulating noradrenaline and adrenaline [85]. This high sympathetic tone leads to increased output of neutrophils and inflammatory monocytes from the bone marrow, cytokine production, and a heightened cell-mediated immune response [84].

Contemporarily, chronic pain is understood as centralized in the sense that pain would be intensified by central nervous processes and dysfunctions. Apart from pain, these processes often coincide with problems sleeping and memorizing, as well as fatigue, anxiety, or depression [86].

Independently from states of chronic pain, research suggests psychopathologic syndromes such as depression or anxiety to be functionally attached to the hemispheres, suggesting the psychosomatic epiphenomena of chronic pain to possibly be organized in a lateralized manner [32], not unlike the inherently lateralized pattern of limb pain. Hence, some of the repeatedly reported associations between lateralized chronic (shoulder) pain and psychopathology may reflect not only processes of sensitization, but also those of lateralization. Were this the case, then laterality might codetermine maladaptive patterns of adjustment based on differential left and right pathways of neural transmission [87]. Quite obviously, a purely peripheral concept of, e.g., osteoarthritis cannot explain the above outlined pattern of comorbidity. Moreover, centralized pain is less responsive to opioid treatments, further underscoring the clinical significance of this distinction. On the contrary, an unrecognized systematic pattern of association between lateralized pain and psychic as well as psychosomatic epiphenomena may contribute to the heterogeneity and inconclusiveness of the associations reported regarding, e.g., shoulder pain and psychopathology. On this note, a recent review weighed the significance of the reported associations by counting [63] the instances in which a psychological construct proved capable of the prediction of shoulder pain, or not. This illustrative and informative procedure may nevertheless omit the role of supra-ordinate factors such as laterality. In addition to other lateralized

functions of the CNS, its neuroimmunomodulatory impact on the immune system may also indeed be a lateralized activity [88], with differences between the hemispheres pertaining to, e.g., the activation of macrophages involved in phagocytosis, inflammation, cytokine production, and antigen presentation, and to T cell activity affecting not only cellular, but also humoral, immunity. Moreover, with respect to traditional medicine there is the puzzling finding of beneficial effects of contralateral acupuncture on shoulder pain [75]. These are known to unfold on peripheral, spinal, and supraspinal levels [89,90], and they apparently rely on lateralization in terms of mirror symmetry, as well. Acupuncture is thus influential with respect to the antagonization of central sensitization, e.g., by means of segmental inhibition, or the activation of opioid or adrenergic receptors. The precise mechanism by which contralateral acupuncture is capable of mitigating limb pain, however, is unknown, but it likely involves neuroplastic processes of supraspinal origin [91], especially in connection with the anterior cingulate cortex [91]. Although promising, those alternative and complementary methods have nevertheless received only little attention in the literature on shoulder disorders.
