Analgesic effects of intrathecally administered 26RFa, an intrinsic agonist for GPR103, on formalin test and carrageenan test in rats.

GPR103 is known as an orphan G protein-coupled receptor. 26RFa and QRFP are endogenous ligands of GPR103. GPR103 mRNA has been reported to be highly expressed in the superficial layers of the entire spinal cord and a high density of 26RFa binding sites was observed in the superficial layers of the dorsal horn. In the present study, the effects of spinally applied 26RFa were tested in the rat. Intrathecal injection of 26RFa significantly decreased the frequency of agitation behaviors induced by paw formalin injection, and attenuated the level of mechanical allodynia induced by paw carrageenan injection, in a dose dependent manner at doses between 0.01 and 10 microg. Intrathecal injection of 26RFa had no effect in both the 52.5 degrees C hotplate test and the mechanical nociceptive test at doses between 0.1 and 10 microg. An immunohistochemical study revealed that GPR103-like immunoreactivity (LI) was observed in the superficial layers of spinal dorsal horn, that QRFP-LI was observed in the dorsal root ganglion and that intrathecal 26RFa suppressed the expression of Fos-LI induced by paw formalin injection in the superficial layers of the spinal dorsal horn. These data suggested that spinally applied 26RFa may modulate spinal sensitization induced by paw formalin injection or paw carrageenan injection.