The Mechanisms By Which P2X₃ And P2Y₁ Receptors Are Involved In The Estrogen Modulation Of Peripheral Pain Signal Transduction

OBJECTIVE: This investigation was undertaken to determine whether the sensory neuron adenosine tnphosphate receptor subunit (P2X₃ and P2Y₁) are involved in modulatory function by estrogen in the peripheral pain transduction in dorsal root ganglia. METHODS: Peripheral pain threshold test, real-time quantitative reverse transcription-polymerase chain reaction analysis, immunohistochemical methods and patch clamp recording were used to determine the mean relative concentrations of the P2X₃ and P2Y₁ receptor in rat dorsal root ganglia in Sham-OP, GDX and E₂-R rats. RESULTS: The peripheral mechanical and thermal pain threshold was decreased and increased respectively after ovariectomy in female rats, while both of them didn't alter significantly after orchiectomy in male rats. The mechanical and thermal pain threshold was increased and decreased significantly after gonadectomy with estradiol replacement. P2X₃mRNA expression was significantly increased while P2Y| mRNA expression wasdecreased after surgical ovariectomy and both were reversed after estrogen replacement. In the cultured DRG neurons, P2X₃ mRNA and P2Y₁ mRNA was significantly decreased and increased respectively 24hrs after application of 17β-estradiol in a concentration dependent manner, which was through estrogen receptors. 17β-estradiol also rapidly inhibited P2X₃ mediated transient current in DRG neurons, with PKA and PKC pathways involved. In colitis rat, P2X₃ mRNA in DRG and colon was significantly increased comparing with those from control group. While in colitis rat after ovariectomy, P2X₃ mRNA in colon but not in DRG was significantly increased comparing with that from OVX group. In DRG cells from colitis rats, 17β-estradiol modulated ATP induced inward currents. CONCLUSIONS: These results suggest that the female gonadal hormone, 17β-estradiol, might participate in control of peripheral pain signal transduction in normal and colitis rats, by modulating P2X₃ and P2Y₁ receptor-mediated events in primary sensory neurons, through non-genomic and genomic mechanisms.