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Molecular pain signalling in joints

Joint pain in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) is only in part explained by inflammatory processes. Neuropeptides and opioids play an important role in the pathogenesis of pain besides proinflammatory cytokines. Molecules like serotonin, histamin, bradykinin and prostaglandins and their receptors are of particular interest. Several research groups have found that these mediators can also be produced from non-neuronal cells. Nerve fibers in RA appear to undergo degenerative processes that lead to a reduction of these fibers [1]. Our group reported the expression of secretoneurin in synovial tissue of patients with RA and OA [2]. In a randomized, double-blind trial, Stein and colleagues demonstrated the efficacy of intra-articular opioid application in chronic arthritis [3]. Other investigators confirmed the antinociceptive and anti-inflammatory effect of opioids [4]. Other neuropeptides, such as the pituitary adenylyl cyclase activating polypeptide, also show anti-inflammatory actions [5]. Evaluated by Taqman real-time PCR, we found a significant reduction of the δ-opioid receptor and the κ-opioid receptor mRNA in synovial fibroblasts in seven patients with RA (κ-opioid receptor, 0.09-fold ± 0.0276, P = 0.037; δ-opioid receptor, 0.05-fold ± 0.0134, P = 0.040) and in seven patients with OA (κ-opioid receptor, 0.15-fold ± 0.0315, P = 0.040; δ-opioid receptor, 0.18-fold ± 0.0561, P = 0.040) compared with in healthy controls.

The investigation of pain-modulating molecules is an important task in pain research. The search for novel pathogenetic mechanisms involving neuropeptides and opioids/opioid receptors should improve the management of pain in patients with RA and OA.

References

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    Sprott H, et al: J Rheumatol. 2000, 27: 2347-2350.

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    Stein , et al: Pain. 1999, 83: 525-532. 10.1016/S0304-3959(99)00156-6.

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    Takeba , et al: J Rheumatol. 2001, 28: 2176-2183.

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    Abad , et al: J Immunol. 2001, 167: 3182-3189.

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Acknowledgement

Dr Shen was supported by the Zurzach foundation.

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Keywords

  • Rheumatoid Arthritis
  • Histamin
  • Bradykinin
  • Adenylyl Cyclase
  • Synovial Tissue