Pain

In previous research work of our group, the presence of several pain-relevant molecules has been explored and detected in peripheral non-neuronal tissues. The functional characteristics of the pathways involving these molecules have also been successfully examined. Thus, the expression of kappa and delta opioid receptors (KOR and DOR) has been demonstrated outside the nervous system in the skin of healthy volunteers (Salemi et al. 2005). More recently, the up-regulation of delta-opioid receptors and kappa-opioid receptors has been shown in the skin from fibromyalgia patients (Salemi et al. 2007). In a related study, the kappa and delta opioid receptors were found to be expressed but down-regulated in synovial fibroblasts of patients with rheumatoid arthritis and osteoarthritis compared to normal synovial fibroblasts (Shen et al. 2005). In searching for the modulation of these receptors, we have noted that the selective KOR agonist U69593 enhanced the expression of KOR mRNA in both OA and RA in a KOR antagonist-reversible manner. To simulate the conditions of inflammation, we demonstrated that the pro-inflammatory cytokines TNFalpha and IL-1beta suppressed the expression of DOR and KOR mRNA in both OA and RA, leading to the conclusion that DOR and KOR receptors are constitutively present in normal synovial fibroblasts, but are suppressed under inflammatory conditions such as RA and OA. This study was awarded the 2nd price in basic research (Deutsche Gesellschaft zum Studium des Schmerzes, 2005).

Publications

Reisch N, Engler A, Aeschlimann A, Simmen BR, Michel BA, Gay RE, Gay S, Sprott H. DREAM is reduced in synovial fibroblasts of patients with chronic arthritic pain: is it a suitable target for peripheral pain management? Arthritis Res Ther 2008, 10:R60. [Epub ahead of print]

Salemi S, Aeschlimann A, Wollina U, Gay RE, Michel BA, Gay S, Sprott H. Up-regulation of delta-opioid receptors and kappa-opioid receptors in the skin of fibromyalgia patients. Arthritis Rheum 2007, 56:2464-6.

Salemi S, Aeschlimann A, Reisch N, Jüngel A, Gay RE, Heppner FL, Michel BA, Gay S, Sprott H. Detection of kappa and delta opioid receptors in skin - outside the nervous system. Biochem Biophys Res Commun 2005, 338:1012-7.

Shen H, Aeschlimann A, Reisch N, Gay RE, Simmen BR, Michel BA, Gay S, Sprott H. Kappa and delta opioid receptors are expressed but down-regulated in fibroblast-like synoviocytes of patients with rheumatoid arthritis and osteoarthritis. Arthritis Rheum 2005, 52:1402-10.

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