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Inhibitory effects of kinase inhibitors and atypical analgesics on hiPSC nociceptors The inhibitory impact of various kinase inhibitors as well as atypical serotonin-norepinephrine reuptake inhibitor (SNRI) and tricyclic antidepressant (TCA) analgesics on the activity of hiPSC nociceptors following a 28-day culture period is evaluated. (A)–(C) and (D)–(F) represent data obtained using dasatinib (a multiple tyrosine kinase inhibitor) and baricitinib (a JAK1/2 inhibitor), respectively. (G)–(I) and (J)–(L) represent data obtained using duloxetine (SNRI) and <t>amitriptyline</t> (TCA), respectively. For each inhibitor, the percentage of inhibition of neuronal activity at 37°C and 47°C is shown (A), (B), (D), (E), (G), (H), (J), and (K) and was calculated relative to 37°C or 42°C baseline, respectively. Additionally, the spike rate of hiPSC nociceptors was monitored for 10 min before and after treatment with the respective blocker (C), (F), (I), and (L) at 37°C to evaluate acute effects (6 wells for each concentration). Pilot studies were conducted to determine the effective concentration range. Data are presented as mean ± SEM (standard error of the mean). See also for statistical comparisons and for relevant gene expression for these targets.
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Inhibitory effects of kinase inhibitors and atypical analgesics on hiPSC nociceptors The inhibitory impact of various kinase inhibitors as well as atypical serotonin-norepinephrine reuptake inhibitor (SNRI) and tricyclic antidepressant (TCA) analgesics on the activity of hiPSC nociceptors following a 28-day culture period is evaluated. (A)–(C) and (D)–(F) represent data obtained using dasatinib (a multiple tyrosine kinase inhibitor) and baricitinib (a JAK1/2 inhibitor), respectively. (G)–(I) and (J)–(L) represent data obtained using duloxetine (SNRI) and <t>amitriptyline</t> (TCA), respectively. For each inhibitor, the percentage of inhibition of neuronal activity at 37°C and 47°C is shown (A), (B), (D), (E), (G), (H), (J), and (K) and was calculated relative to 37°C or 42°C baseline, respectively. Additionally, the spike rate of hiPSC nociceptors was monitored for 10 min before and after treatment with the respective blocker (C), (F), (I), and (L) at 37°C to evaluate acute effects (6 wells for each concentration). Pilot studies were conducted to determine the effective concentration range. Data are presented as mean ± SEM (standard error of the mean). See also for statistical comparisons and for relevant gene expression for these targets.
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Inhibitory effects of kinase inhibitors and atypical analgesics on hiPSC nociceptors The inhibitory impact of various kinase inhibitors as well as atypical serotonin-norepinephrine reuptake inhibitor (SNRI) and tricyclic antidepressant (TCA) analgesics on the activity of hiPSC nociceptors following a 28-day culture period is evaluated. (A)–(C) and (D)–(F) represent data obtained using dasatinib (a multiple tyrosine kinase inhibitor) and baricitinib (a JAK1/2 inhibitor), respectively. (G)–(I) and (J)–(L) represent data obtained using duloxetine (SNRI) and amitriptyline (TCA), respectively. For each inhibitor, the percentage of inhibition of neuronal activity at 37°C and 47°C is shown (A), (B), (D), (E), (G), (H), (J), and (K) and was calculated relative to 37°C or 42°C baseline, respectively. Additionally, the spike rate of hiPSC nociceptors was monitored for 10 min before and after treatment with the respective blocker (C), (F), (I), and (L) at 37°C to evaluate acute effects (6 wells for each concentration). Pilot studies were conducted to determine the effective concentration range. Data are presented as mean ± SEM (standard error of the mean). See also for statistical comparisons and for relevant gene expression for these targets.

Journal: Cell Reports Methods

Article Title: Profiling human iPSC-derived sensory neurons for analgesic drug screening using a multi-electrode array

doi: 10.1016/j.crmeth.2025.101051

Figure Lengend Snippet: Inhibitory effects of kinase inhibitors and atypical analgesics on hiPSC nociceptors The inhibitory impact of various kinase inhibitors as well as atypical serotonin-norepinephrine reuptake inhibitor (SNRI) and tricyclic antidepressant (TCA) analgesics on the activity of hiPSC nociceptors following a 28-day culture period is evaluated. (A)–(C) and (D)–(F) represent data obtained using dasatinib (a multiple tyrosine kinase inhibitor) and baricitinib (a JAK1/2 inhibitor), respectively. (G)–(I) and (J)–(L) represent data obtained using duloxetine (SNRI) and amitriptyline (TCA), respectively. For each inhibitor, the percentage of inhibition of neuronal activity at 37°C and 47°C is shown (A), (B), (D), (E), (G), (H), (J), and (K) and was calculated relative to 37°C or 42°C baseline, respectively. Additionally, the spike rate of hiPSC nociceptors was monitored for 10 min before and after treatment with the respective blocker (C), (F), (I), and (L) at 37°C to evaluate acute effects (6 wells for each concentration). Pilot studies were conducted to determine the effective concentration range. Data are presented as mean ± SEM (standard error of the mean). See also for statistical comparisons and for relevant gene expression for these targets.

Article Snippet: Amitriptyline , Chem-Impex , Cat#37560.

Techniques: Activity Assay, Inhibition, Concentration Assay, Gene Expression