Lack of tactile pain (allodynia) in lipocalin-type prostaglandin D synthase-deficient mice.
Prostaglandin (PG) D2 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 PGD2 synthase (L-PGDS) and found that the intrathecal administration of PGE2, 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 gamma-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 PGD2 with PGE2 or bicuculline induced allodynia in L-PGDS-/- mice to the same extent as in wild-type mice. The PGE2- or bicuculline-evoked allodynia in wild-type and in PGD2-supplemented L-PGDS-/- mice was blocked by a PGD2 receptor antagonist given in a femtogram amount. These results reveal that endogenous PGD2 is essential for both PGE2- and bicuculline-induced allodynia.
Eguchi
N
N
Precursory Research for Embryonic Science and Technology, Japan Science and Technology Corporation, Department of Morphological Brain Science, Faculty of Medicine, Kyoto University, Sakyo, Kyoto 606-8315, Japan.
Minami
T
T
Shirafuji
N
N
Kanaoka
Y
Y
Tanaka
T
T
Nagata
A
A
Yoshida
N
N
Urade
Y
Y
Ito
S
S
Hayaishi
O
O
D000758:Anesthesia; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002490:Central Nervous System / Q000503:physiopathology; D015237:Dinoprost / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018390:Gene Targeting / Q000379:methods; D006827:Hydantoins / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology; D007150:Immunohistochemistry; D019746:Intramolecular Oxidoreductases / Q000172:deficiency / Q000235:genetics*; D054834:Lipocalins; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010146:Pain / Q000235:genetics* / Q000503:physiopathology; D015230:Prostaglandin D2 / Q000494:pharmacology; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors
D018756:GABA Antagonists; D006827:Hydantoins; D054834:Lipocalins; D011982:Receptors, Prostaglandin; C058848:BW A868C; C030669:BW 245C; D015237:Dinoprost; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D015232:Dinoprostone; D015230:Prostaglandin D2; D001640:Bicuculline