Lack of tactile pain (allodynia) in lipocalin-type prostaglandin D synthase-deficient mice

Abstract

Prostaglandin (PG) D 2 is the most abundant prostanoid produced in the central nervous system of mammals and has been implicated in the modulation of neural functions such as sleep induction, nociception, regulation of body temperature, and odor responses. We generated gene-knockout mice for lipocalin-type PGD 2 synthase (L-PGDS) and found that the intrathecal administration of PGE 2 , an endogenous pain-producing substance, failed to elicit allodynia (touch-evoked pain), which is one typical phenomenon of neuropathic pain, whereas it evoked thermal hyperalgesia, in L-PGDS−/− mice. We also found that the allodynic response induced by the γ-aminobutyric acid (GABA) A receptor antagonist bicuculline was selectively abolished in the L-PGDS−/− mice, among excitatory and inhibitory agents that induced allodynia in wild-type mice. Interestingly, simultaneous injection of a femtogram amount of PGD 2 with PGE 2 or bicuculline induced allodynia in L-PGDS−/− mice to the same extent as in wild-type mice. The PGE 2 - or bicuculline-evoked allodynia in wild-type and in PGD 2 -supplemented L-PGDS−/− mice was blocked by a PGD 2 receptor antagonist given in a femtogram amount. These results reveal that endogenous PGD 2 is essential for both PGE 2 - and bicuculline-induced allodynia.