Question: 

Prostaglandin E₂ (PGE₂) is known to sensitize TRPV1 to heat in peripheral nociecptors (Moriyama et al., 2005, Mol Pain, 1:3). Our aim was to determine whether PGE₂ could also directly activate DRG neurons in primary culture and to investigate the signaling pathway involved in the response.

Methodology: 

Primary DRG cultures we obtained from adult male Wistar rats. The calcium microfluorimetry technique was used to monitor changes in intracellular calcium concentrations ([Ca²⁺]_i) evoked by PGE₂ (10 mM), capsaicin (2 mM), AH13205 (EP2-receptor agonist) and sulprostone (EP3-receptor agonist) (both at 1 mM).

Results: 

At a temperature of 25 °C, PGE₂ evoked increases in [Ca²⁺]_i in ca. 23% of DRG neurons (24/84) and all these PGE2-sensitive neurons were also activated by capsaicin. The neuronal response to PGE₂ was mainly due to calcium entry, as it was strongly diminished (by ca. 79%) when PGE₂ was applied in a calcium-free external solution. The PGE₂-induced response was fully and reversibly blocked by co-application with the selective TRPV1 antagonists capsazepine and SB366791. While the EP2 agonist AH13205 activated only 21% of PGE₂-sensitive neurons and the EP3 agonist sulprostone failed to activate any PGE₂-sensitive neuron, the selective EP1-receptor antagonist SC19220 (100 nM) strongly (ca. 82%) and reversibly inhibited the neuronal response to PGE₂, indicating that the direct activation of DRG neurons by PGE₂ is mediated primarily by EP1.

Conclusion: 

PGE2 application evokes fast increases in [Ca²⁺]_i in cultured DRG neurons, via activation of its EP1 receptor, followed by TRPV1 channel opening and calcium entry.