LPS-induced knee-joint reactive arthritis and spinal cord glial activation were reduced after intrathecal thalidomide injection in rats

AimsThalidomide is thought to prevent TNF-α production, and such mechanism could be useful in a spinally delivered drug approach for the control of peripheral inflammation. This study aimed to evaluate the effect of intrathecal thalidomide, in comparison with that of intraperitoneal treatment, on articular incapacitation, edema, synovial leukocyte content, and spinal cord glial activation in a model of Escherichia coli lipopolysaccharide (LPS)-induced reactive arthritis in rats.Main methodsLPS (30 ng) was injected into a knee-joint previously primed with carrageenan (300 μg). Systemic (30 and 100 mg/kg; intraperitoneal, i.p.) and intrathecal (10 and 100 μg; i.t.) thalidomide were given 1 h or 20 min before LPS injection, respectively. Articular incapacitation and edema were evaluated hourly. After 6 h, synovial fluid and lumbar spinal cords were collected for subsequent evaluations of cell migration and expression of CD11b/c and GFAP markers, respectively.Key findingsSystemic (30 and 100 mg/kg) or intrathecal (10 and 100 μg) thalidomide reduced articular incapacitation, edema, and polymorphonuclear migration. In addition, i.p. and i.t. thalidomide reduced the expression of CD11b/c and GFAP markers in the lumbar spinal cord. These results suggest that thalidomide can also produce peripheral anti-inflammatory effects through action in the spinal cord that may involve glia inhibition.SignificanceThis study provides new evidence that the direct spinal delivery of immunomodulators may be an alternative for the treatment of arthritic diseases, which require long systemic treatment with drugs associated with undesirable side effects.