| Previous investigations demonstrate that prostaglandin (PG) and prostaglandinsynthase play important roles in the progress of inflammation and pain modulation.The inhibitors of prostaglandin synthase are used as antipyretic-analgesic andanti-inflammatory drugs and the cyclooxygenase is the target for nonsteroidalanti-inflammatory agents that effectively reduce the pain induced by various tissueinflammations. However, these agents could lead to many side effects if they are usedfor the patients of long-term treatment. Thus, more promising strategy is to study onthe mechanism of the prostaglandin synthase in pain modulation, enablingdevelopment of new and effective anti-inflammatory agents with fewer side effects.Lipocalin-type prostaglandin D synthase (L-PGDS) is known as the brain-typeenzyme or glutathione-independent enzyme and catalyzes the isomerization of PGH2,a common precursor of various prostanoids, to produce PGD2, a potent nociceptivemodulator. In the present study, the distribution of L-PGDS and its regulation duringchronic pain were investigated in primary sensory ganglion. The immunostainingshowed that L-PGDS distributed in small-sized DRG neurons and colocalized withcalcitonin gene-related peptide. The L-PGDS displayed a vesicular structure thatcontained calcitonin gene-related peptide. Furthermore, in animal models of sciaticnerve axotomy and chronic inflammation, the gene expression of L-PGDS wasupregulated in dorsal root ganglion using both microarray and RT-PCR after completeFreund's adjuvant-induced chronic inflammation and peripheral nerve injury. Finally,preliminary data showed that intrathecal delivery of PGD2 induced mechanicalallodynia and intrathecal injection of the selective PGD2 receptor antagonistsignificantly decreased the mechanical allodynia in animal model of chronicinflammation. These results suggest that L-PGDS could involve in the developmentand maintenance of chronic pain. Our study provides a mechanism in searching fordrug target of analgesia. |
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