Ocular Manifestations of Chikungunya Infection: A Systematic Review.

The Chikungunya virus (CHIKV) can cause long lasting symptoms and manifestations. However, there is little information on which ocular ones are most frequent following infection. We performed a systematic review (registered in the International Prospective Register of Systematic Reviews; no CRD42020171928) to establish the most frequent ocular manifestations of CHIKV infection and their associations with gender and age. Articles published until September 2020 were selected from PubMed, Scielo, Cochrane and Scopus databases. Only studies with CHIKV-infected patients and eye alterations were included. Reviews, descriptive studies, or those not investigating the human ocular manifestations of CHIKV, those with patients with other diseases and infections, abstracts and studies without relevant data were excluded. Twenty-five studies were selected for inclusion. Their risk of bias was evaluated by a modified Newcastle-Ottawa scale. The most frequent ocular symptoms of CHIKV infection included ocular pain, inflammation and reduced visual acuity, whilst conjunctivitis and optic neuritis were the most common manifestations of the disease. These occurred mostly in individuals of 42 ± 9.5 years of age and woman. The few available reports on CHIKV-induced eye manifestations highlight the need for further research in the field to gather more substantial evidence linking CHIKV infection, the eye and age/gender. Nonetheless, the data emphasizes that ocular alterations are meaningful occurrences of CHIKV infection which can substantially affect quality of life.

Calcitonin Gene-Related Peptide Protects Against Cardiovascular Dysfunction Independently of Nitric Oxide In Vivo.

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Hydrogen peroxide is a novel mediator of inflammatory hyperalgesia, acting via transient receptor potential vanilloid 1-dependent and independent mechanisms.

Inflammatory diseases associated with pain are often difficult to treat in the clinic due to insufficient understanding of the nociceptive pathways involved. Recently, there has been considerable interest in the role of reactive oxygen species (ROS) in inflammatory disease, but little is known of the role of hydrogen peroxide (H(2)O(2)) in hyperalgesia. In the present study, intraplantar injection of H(2)O(2)-induced a significant dose- and time-dependent mechanical and thermal hyperalgesia in the mouse hind paw, with increased c-fos activity observed in the dorsal horn of the spinal cord. H(2)O(2) also induced significant nociceptive behavior such as increased paw licking and decreased body liftings. H(2)O(2) levels were significantly raised in the carrageenan-induced hind paw inflammation model, showing that this ROS is produced endogenously in a model of inflammation. Moreover, superoxide dismutase and catalase significantly reduced carrageenan-induced mechanical and thermal hyperalgesia, providing evidence of a functionally significant endogenous role. Thermal, but not mechanical, hyperalgesia in response to H(2)O(2) (i.pl.) was longer lasting in TRPV1 wild type mice compared to TRPV1 knockouts. It is unlikely that downstream lipid peroxidation was increased by H(2)O(2). In conclusion, we demonstrate a notable effect of H(2)O(2) in mediating inflammatory hyperalgesia, thus highlighting H(2)O(2) removal as a novel therapeutic target for anti-hyperalgesic drugs in the clinic.

Capsaicin-induced vasoconstriction in the mouse knee joint: a study using TRPV1 knockout mice.

Capsaicin is the pungent component of chilli peppers that concomitantly activates and desensitizes C-fibre and Adelta sensory nerve fibres. Stimulation causes an acute neurogenic response including vasodilation, plasma extravasation and hypersensitivity. However, in the present study we have shown that capsaicin produces a dose-dependent vasoconstrictor effect in the mouse knee joint via Transient Receptor Potential Vanilloid 1 (TRPV1) receptor activation. A (125)I-albumin accumulation technique showed that the intravascular volume of capsaicin-treated joints in wild type (WT) mice was significantly reduced compared to TRPV1 knockout mice (p<0.01). Similarly, a laser Doppler technique showed significantly reduced blood flow in the capsaicin-treated joints of WT compared to TRPV1 knockout mice (p<0.001). Pretreatment with guanethinidine (50 mg kg(-1), i.p.) had no effect on the vasoconstriction. These data are important considering the involvement of TRPV1 receptors in joint disease. The mechanisms underlying the vasoconstriction therefore require further investigation.

The role of substance P in microvascular responses in murine joint inflammation.

1. Rheumatoid arthritis is a serious, inflammatory disease of the distal joints that has a possible neurogenic component underlying its pathology. 2. Substance P (SP), an endogenous neuropeptide that acts upon the neurokinin 1 (NK(1)) receptor, is released from sensory nerves and is involved in neurogenic inflammation. 3. In this study, we have developed novel techniques to determine the contribution of SP to microvascular responses in a model of complete Freund's adjuvant (CFA)-induced arthritis in NK(1) knockout mice. 4. Detailed analysis in normal mice revealed that CFA (20 microg i.art.)-induced plasma extravasation was raised from 18 to 72 h, when compared with intravascular volume. By comparison, knee swelling was sustained for 3 weeks. Neutrophil accumulation mirrored plasma extravasation. SP (10 pmol i.art.) caused significant acute plasma extravasation, but not other parameters, in wild type (WT), but not NK(1) knockout mice. CFA (10 microg i.art.) induced a significantly decreased intravascular volume, presumably due to decreased blood flow, at early time points (5 and 7 h) in WT but not NK(1) knockouts. Otherwise, similar responses in WT and NK(1) knockout mice were observed. However, injection of SP into CFA-pretreated joints caused a significant enhancement of plasma extravasation and knee swelling in the WT but not NK(1) knockouts. 5. In conclusion, the present study has used novel techniques in WT and NK(1) knockout mice to show that SP can modulate vascular tone and permeability in the inflamed joint via activation of the NK(1) receptor and that SP-induced responses are more pronounced where pre-existing inflammation is present.