Sulfated polysaccharide from the green marine algae Caulerpa racemosa reduces experimental pain in the rat temporomandibular joint

Abstract Temporomandibular disorder is a clinical painful condition in the temporomandibular joint (TMJ) region. The purified sulfated polysaccharide from the green marine algae Caulerpa racemosa (Cr) has provided anti-inflammatory and antinociceptive activity. This study evaluated these effects on a TMJ hypernociception model. Wistar rats (180 - 250 g) were pre-treated (i.v.) with Cr at 0.01, 0.1, or 1 mg/kg or vehicle 30 min before formalin (1.5%/50 μL, i.art.), capsaicin (1.5%/20 μL, i.art.), or serotonin (225 μg/50 μL, i.art.) in the TMJ, and nociceptive behaviors were measured for 45 or 30 min upon inflammatory stimuli. Inflammatory parameters vascular permeability assay, TNF-α, and IL-1β by ELISA, protein expression of adhesion molecules ICAM-1 and CD55 by Western blot were assessed. The involvement of heme oxygenase-1 (HO-1) and nitric oxide (NO) pathways were assessed by pharmacological inhibition. Cr (1 mg/kg) reduced nociceptive behavior, plasmatic extravasation, TNF-α, and IL-1β levels, as well as ICAM-1 and CD55 expression in periarticular tissues. Cr antinociceptive effect was not prevented by aminoguanidine, but ZnPP-IX did reduce its antinociceptive effect. Therefore, Cr antinociceptive and anti-inflammatory effects in this experimental model of hypernociception depended on the HO-1 pathway integrity, as well as reducing peripheral inflammatory events, e.g., TNF-α and IL-1β cytokines levels, ICAM-1 and CD55 expression.