Tissue damage following injury triggers the processes of coagulation, inflammation and healing. In tissues surrounding the bone, the result of the healing process is a scar, while bone tissue has a unique ability to achieve shape, strength and pre-injury function. Bone healing is a process of regeneration rather than classic recovery. The result of this process is the formation of new, healthy bone tissue instead of a scar. Many factors can inhibit or impair the bone healing process, and their influence is critical during the stages of inflammation and angiogenesis and finally on the clinical outcome. Nonsteroidal anti-inflammatory drugs (NSAIDs) play an essential role associated with their analgesic potency and anti-inflammatory effects. NSAIDs are also the most often used drugs in patients who require pain control and inflammation reduction due to musculoskeletal diseases or injures. Although their analgesic effect is well documented, NSAIDs also interfere with bone healing; therefore, the relative benefits and disadvantages connected with their administration should be taken into consideration. Despite the negative effect, NSAIDs have beneficial properties, but their clinical benefits in relation to dose and time of use are still unclear. Therefore, in this review, we focus on bone healing with relation to the impact of NSAIDs.

In this review, we discuss the current data about the anatomy and function of bone tissue with particular regard to influence of prostaglandins. Bone tissue dynamics are characterized by a constant remodeling process that involves all bone tissue cells. The communication between bone component cells and other organs is necessary for bone remodeling equilibrium and confirms the dynamic character of bone tissue. Remodeling is also a vital element of healing processes and in adapting bone tissue to stress responses. Therefore, in our review we present the role and significance of bone cells and signaling pathways enabling maintenance of bone homeostasis and remodeling process stability. Cyclooxygenase (COX) is a crucial enzyme in the production of prostaglandins and thromboxane. We focus on the role of COX isoenzymes with highlighting their connection with bone formation, resorption and repair. Prostaglandins are known as arachidonic acid metabolites acting through specific membrane receptors and play an important role in the regulation of osteoblast and osteoclast functions. Prostaglandin PGE2 with its four defined receptors (EP1R, EP2R, EP3R and EP4R) is crucial to maintain balanced bone turnover. Their stimulatory or inhibitory effects appear to depend on different structure-activity relations and signaling pathways. We have described the role of these receptors in bone metabolism and healing. We conclude that the activity of prostaglandins in bone tissue is defined by maintaining bone remodeling balance and its reactions to humoral mediators and mechanical stress. Most data confirm that among prostaglandins, PGE2 takes part in all processes of trauma response, including homeostasis, inflammation and healing, and plays a key role in bone physiology.

Fibromyalgia (FM) is considered a multifactorial disorder/syndrome with not fully understood etiology. Chronic generalized pain is the main symptom. A broad spectrum of factors is proposed to ex-plain the etiology. Its multifactorial nature is inherently associated with challenges in diagnosis and therapy. Various evidence of etiology has been evaluated with the aim of establishing a novel therapeutic approach. The main issue in the diagnosis and management is to focus on the evaluation of strict diagnostic criteria to minimize under- and overdiagnosis. Fibromyalgia is a challenge for perioperative management because of the increased risk of possible complications and poorer out-comes, including postoperative pain chronification. The authors have proposed an up-to-date evaluation of perioperative management considering the current guidelines. Multimodal analgesia combined with tailored perioperative care is the most appropriate assessment. Interdisciplinary research with special interest in pain management, including perioperative medicine, seems to be the main theme for the future.

Objectives (1) To compare spontaneous and stimuli-induced adipocytokine secretion by articular adipose tissue (AAT) and synovial membrane (SM) explants obtained from patients with rheumatoid arthritis (RA). (2) To investigate the biological activity of AAT and SM released factors. Methods Tissues were obtained from patients undergoing joint replacement surgery. Tissue explants were treated with proinflammatory cytokines relevant to RA pathogenesis (interleukin 1β (IL-1β), tumour necrosis factor (TNF), interferon γ, IL-15, IL-17, IL-23). Selected adipocytokine (TNF, IL-6, IL-8, IL-1β, IL-1Ra, adiponectin, leptin) concentrations were measured in culture supernatants using ELISA. The biological activity of tissue-conditioned media was evaluated by measuring production of selected factors (IL-6, IL-8, Dickkopf-1, osteoprotegerin) by fibroblast-like synoviocytes (FLS). Results Spontaneous cytokine release from AAT was ≤12% of that produced by SM, while leptin was secreted in similar amounts. AAT was highly reactive to proinflammatory cytokines (IL-1β>TNF). AAT treated with IL-1β released four times more leptin, similar amounts of IL-6 and IL-8 and about 20% of TNF, as compared with SM. Upon activation, the IL-1 receptor antagonist (IL-1Ra)/IL-1β ratio was higher in AAT than in SM cultures. Irrespective of activation status, SM produced twice as much adiponectin as AAT. Conditioned media from AAT and SM cultures similarly upregulated IL-6, IL-8, Dickkopf-1 and osteoprotegerin production by rheumatoid FLS. Conclusion Rheumatoid AAT is highly reactive tissue which upon stimulation secretes considerable amounts of proinflammatory (IL-6, IL-8, TNF) and anti-inflammatory (IL-1Ra) cytokines and classical adipokines. This tissue releases biologically active factors that intensify pathogenic activities of rheumatoid FLS. Thus, AAT should be considered an important contributor to the pathological processes taking place in the RA joint.

Evidence suggests that substance P (SP) is involved in chronic joint inflammation, such as the pathogenesis of rheumatoid arthritis and osteoarthritis. The goal of the research was to evaluate the correlation between chronic pain and changes in the SP level in patients with chronic inflammation of the connective tissue. Patients with osteoarthritis and rheumatoid arthritis were enrolled in this study. The relationship between chronic pain intensity and the serum SP concentration was evaluated in these groups of patients with osteoarthritis and rheumatoid arthritis. The results showed a positive correlation between the serum SP concentrations and chronic pain intensity. 1. The SP serum concentration was significantly different between the groups of patients with OA and RA. 2. There was a positive correlation between the serum SP concentration and chronic pain intensity in OA and RA patients.