Figure 1.

mGlu2/3 receptor activation blocks PGE₂-induced TRPV1 sensitization in mouse, but not human, sensory neurons. Representative traces of 100 nm capsaicin (Cap)-induced calcium responses in mouse (A) and human (B) DRG neurons in response to vehicle (left), 1 μm PGE₂ (middle), or 1 μm PGE₂ + 10 μm APDC (right). Experiments concluded with a pulse of 50 mm KCl to determine cell viability. The degree of TRPV1 sensitization is expressed as a response ratio calculated by dividing the peak amplitude of Cap 2 by the peak amplitude of Cap 1 (A, dashed lines). C, In mouse DRG neurons, PGE₂ significantly increased the capsaicin response ratio compared with vehicle (**** p = 2.1 × 10^–5; n = 143–150 neurons, n = 4 preps/condition). Coapplication of APDC with PGE₂ blocked this effect and significantly reduced the response ratio compared to PGE₂ alone (** p = 0.0081; n = 89–150 neurons, n = 3–4 preps/condition). D, PGE₂ also significantly increased the capsaicin response ratio of human DRG neurons compared with vehicle (**** p = 3.0 × 10^–6; n = 59–71 neurons, n = 5–6 donors/condition); whereas coapplication of APDC did not suppress PGE₂-induced increases in the capsaicin response ratio (p = 1, n = 59–64 neurons, n = 6 donors/condition), which remained significantly greater than vehicle (** p = 0.0053, n = 64–71 neurons, n = 5–6 donors/condition). Capsaicin response ratios were compared using unpaired t tests and a Bonferroni correction for multiple comparisons. Data are presented as mean ± SEM. E, Compared with those of mice, a greater percentage of human DRG neurons responded to 100 nm capsaicin (χ² = 15.45, **** p = 8.5 × 10^–5, mouse: 405/1761 neurons, n = 4 preps, human: 223/731 neurons, n = 8 donors). F, LMM regression correction for impact of individual donor, as well as donor age and sex, did not alter human capsaicin response ratio analysis statistical outcomes compared with t tests alone.