Background and Objectives: Musculoskeletal dysfunction can induce several types of chronic pain syndromes. It is of particular interest to elucidate the pathomechanism of different forms of chronic pain. It is possible that patients who have developed chronic widespread pain (CWP) may endure different pathomechanisms as compared to those who suffer from local pain (osteoarthritis, OA) and regional pain (chronic low back pain, cLBP), especially with regard to pain regulation and its related biomediators. The aim of this study was to determine the differences in pathomechanisms among these patients by measuring pain-related biomediators, particularly brain-derived neurotrophic factor (BDNF). Additionally, subpopulations of immune cells were determined in parallel. Materials and Methods: Patients and healthy subjects (HSs) were recruited (age and gender-matched). BDNF was measured from serum samples of patients and HSs and the data of body composition parameters were recorded. Additionally, both patients and HSs were asked to fill in questionnaires related to pain intensity, anxiety, and depression. Results: Our results highlight that the levels of both free and total BDNF are significantly lower in pain patients compared to HSs, with p values of 0.041 and 0.024, respectively. The number of CD3− CD56bright natural killer (NK) cells shows significant differences between the groups. Comparing all chronic pain patients with HSs reveals a significantly lower number of CD4+ CD8+ T cells (p = 0.031), CD3− CD56bright NK cells (p = 0.049) and CD20+ CD3− cells (p = 0.007). Conclusions: To conclude, it seems that a general conformity between the pathomechanisms of different chronic pain diseases exists, although there are unique findings only in specific chronic pain patients.