prostaglandin-d2 and Temporomandibular-Joint-Disorders

Painful conditions of the temporomandibular joint (TMJ) are challenging to manage and most attempts often result in unsatisfactory outcomes. In such context, nanocarrier systems, such as polymeric micelles, have been showing encouraging results in solving therapeutic limitations. Poloxamers are widely used, especially PL 407, because of their high biocompatibility and approval by the Food and Drug Administration (FDA) for clinical use. 15-deoxy-

Topics: Animals; Anti-Inflammatory Agents; Arthralgia; Biological Availability; Chemotaxis, Leukocyte; Cytokines; Disease Models, Animal; Drug Carriers; Drug Compounding; Formaldehyde; Inflammation Mediators; Injections, Intra-Articular; Leukocytes; Male; Micelles; Poloxamer; Prostaglandin D2; Rats, Wistar; Temporomandibular Joint; Temporomandibular Joint Disorders; Tissue Distribution

The pain arising from temporomandibular disorders is often treated with opioids and agents that inhibit the immune response and are associated with substantial adverse effects and long-term risks. Thus, the development of new therapies that are safer and more effective is of great interest to patients and clinicians. 15-deoxy-Δ

Topics: Administration, Cutaneous; Animals; Anti-Inflammatory Agents; Cytokines; Drug Delivery Systems; Excipients; Hyaluronic Acid; Injections, Intra-Articular; Microinjections; Needles; Nociception; Pain; Permeability; Prostaglandin D2; Rats, Wistar; Skin; Temporomandibular Joint; Temporomandibular Joint Disorders; Tissue Distribution

The aim of this study was to evaluate the peripheral effect of 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) in albumin-induced arthritis in temporomandibular joint (TMJ) of rats. Antigen-induced arthritis (AIA) was generated in rats with methylated bovine serum albumin (mBSA) diluted in complete Freund׳s adjuvant. Pretreatment with an intra-articular injection of 15d-PGJ2 (100 ng/TMJ) before mBSA intra-articular injection (10 µg/TMJ) (challenge) in immunized rats significantly reduced the albumin-induced arthritis inflammation. The results demonstrated that 15d-PGJ2 was able to inhibit plasma extravasation, leukocyte migration and the release of inflammatory cytokines IL-6, IL-12, IL-18 and the chemokine CINC-1 in the TMJ tissues. In addition, 15d-PGJ2 was able to increase the expression of the anti-adhesive molecule CD55 and the anti-inflammatory cytokine IL-10. Taken together, it is possible to suggest that 15d-PGJ2 inhibit leukocyte infiltration and subsequently inflammatory process, through a shift in the balance of the pro- and anti-adhesive properties. Thus, 15d-PGJ2 might be used as a potential anti-inflammatory drug to treat arthritis-induced inflammation of the temporomandibular joint.

Topics: Animals; Anti-Inflammatory Agents; Antigens; Arthritis, Experimental; CD55 Antigens; Cell Movement; Cytokines; Freund's Adjuvant; Injections, Intra-Articular; Intercellular Adhesion Molecule-1; Leukocytes; Male; Prostaglandin D2; Rats, Wistar; Serum Albumin, Bovine; Temporomandibular Joint Disorders

Inflammation of the temporomandibular joint (TMJ) induced by rheumatoid arthritis (RA) have resulted in persistent pain and caused distress to many patients. Considering that not all patients respond to traditional drugs therapy to RA and it has demonstrated that 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) into TMJ has a potential peripheral antinociceptive effect, the aim of this study was to evaluate the peripheral effect of 15d-PGJ2 in RA-induced TMJ inflammatory hypernociception.. Antigen-induced arthritis (AIA) was generated in rats with methylated bovine serum albumin (mBSA). RA-induced TMJ hypernociception was assessed by measuring the behavioural nociceptive responses. After behavioural experiments, the animals were terminally anaesthetized and periarticular tissues were removed and homogenized. The supernatants were used to evaluate the levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1β and keratinocyte-derived chemokine (KC) by enzyme-linked immunosorbent assay as well the expression of PKCε and PKA by western blotting analysis.. The intra-articular injection of mBSA, but not phosphate buffered saline (control), in immunized rats induced dose- and time-dependent behavioural nociceptive responses in which the peak of nociceptive responses were obtained by using 10 μg/TMJ of mBSA after 24 h. Pretreatment with 15d-PGJ2 (30, 100 and 300 ng/TMJ) inhibited the RA-induced TMJ inflammatory hypernociception. In addition, 15d-PGJ2 reduced the RA-induced release of TNF-α, IL-1β and KC (p < 0.05) as well the expression of PKA and PKCε (p < 0.05).. In the present study, we demonstrated that 15d-PGJ2 was able to reduce the RA-induced TMJ inflammatory hypernociception by an indirect mechanism. This antinociceptive effect is in part due to decrease of TNF-α, IL-1β and KC levels and PKA/PKCε expression in the TMJ.

Topics: Analgesics; Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Behavior, Animal; Chemokines; Cyclic AMP-Dependent Protein Kinases; Inflammation; Interleukin-1beta; Male; Pain Measurement; Prostaglandin D2; Protein Kinase C-epsilon; Rats; Rats, Wistar; Temporomandibular Joint Disorders; Treatment Outcome; Tumor Necrosis Factor-alpha

To verify whether the nanoencapsulation of 15d-PGJ(2) in poly(D,L-lactide-co-glycolide) (PLGA) nanocapsules (15d-PGJ(2)-NC) might potentialize its antinociceptive activity into rats' temporomandibular joint (TMJ).. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) were used to evaluate the morphology and suspension of the PLGA nanocapsules. Rats were pretreated (15 min) with an intra-TMJ injection of unloaded 15d-PGJ(2) or 15d-PGJ(2)-NC at concentrations of 10, 100 or 1000 pg followed by an ipsilateral intra-TMJ injection of 1.5% formalin. The nociceptive behavioral response was observed during 45 min; animals were then sacrificed and the periarticular tissue was removed for IL-1β measurements.. TEM and AFM analyses showed that 15d-PGJ(2)-NC is spherical without any aggregates or adhesion confirming that this formulation is a good drug carrier system for 15d-PGJ(2). Pretreatment with 15d-PGJ(2)-NC (100 and 1000 pg/TMJ), but not unloaded 15d-PGJ(2), was found to significantly decrease the release of IL-1β cytokine and the animals' nociceptive behavioral response induced by intra-TMJ injection of formalin.. The compound 15d-PGJ(2)-NC might be used as a potential antinociceptive and anti-inflammatory agent to treat temporomandibular disorders in clinical practice.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Behavior, Animal; Dose-Response Relationship, Drug; Drug Carriers; Formaldehyde; Inflammation; Injections; Interleukin-1beta; Lactic Acid; Male; Microscopy, Atomic Force; Microscopy, Electron, Transmission; Nanocapsules; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Prostaglandin D2; Rats; Rats, Wistar; Temporomandibular Joint Disorders

Since it is recognized that cyclo-oxygenase-2 mediates nociception and the sleep-wake cycle as well, and that acute inflammation of the temporomandibular joint (TMJ) results in sleep disturbances, we hypothesized that cyclo-oxygenase-2 inhibitor would restore the sleep pattern in this inflammatory rat model. First, sleep was monitored after the injection of Freund's adjuvant (FA group) or saline (SHAM group) into the rats' temporomandibular joint. Second, etoricoxib was co-administered in these groups. The Freund's adjuvant group showed a reduction in sleep efficiency, in rapid eye movement (REM), and in non-REM sleep, and an increase in sleep and REM sleep latency when compared with the SHAM group, while etoricoxib substantially increased sleep quality in the Freund's adjuvant group. These parameters returned progressively to those found in the SHAM group. Etoricoxib improved the sleep parameters, suggesting the involvement of the cyclo-oxygenase-2 enzyme in acute inflammation of the TMJ, specifically in REM sleep.

Topics: Acute Disease; Animals; Arthritis, Experimental; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Etoricoxib; Male; Prostaglandin D2; Pyridines; Random Allocation; Rats; Rats, Wistar; Sleep Wake Disorders; Sleep, REM; Sulfones; Temporomandibular Joint Disorders