Modelling inflammation-induced peripheral sensitization in a dish-more complex than expected?

TY - JOUR

T1 - Modelling inflammation-induced peripheral sensitization in a dish-more complex than expected?

AU - Li, Yuening

AU - Lock, Amy

AU - Fedele, Laura

AU - Zebochin, Irene

AU - Sabate, Alba

AU - Siddle, Matthew

AU - Cainarca, Silvia

AU - Röderer, Pascal

AU - Montag, Katharina

AU - Tarroni, Paola

AU - Brüstle, Oliver

AU - Shaw, Tanya

AU - Taams, Leonie

AU - Denk, Franziska

N1 - Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.

PY - 2025/2/25

Y1 - 2025/2/25

N2 - Peripheral sensitization of nociceptors is believed to be a key driver of chronic pain states. Here, we sought to study the effects of a modified version of inflammatory soup on the excitability of human stem cell-derived sensory neurons. For this, we used a preexisting and a novel stem cell line, modified to stably express the calcium sensor GCamP6f. Upon treatment with inflammatory soup, we observed no changes in neuronal transcription or functional responses upon calcium imaging and only a very minor increase in resting membrane potential (RMP) via whole cell patch clamping: control RMP (-71.31 ± 1.1 mV) vs inflammatory soup RMP (-67.74 ± 1.29 mV), uncorrected 2-tailed independent samples t test, P = 0.0383. Similarly, small changes were observed when treating mouse primary sensory neurons with inflammatory soup. A semi-systematic reexamination of past literature further indicated that observed effects of inflammatory mediators on dissociated sensory neuron cultures are generally small. We conclude that modelling inflammation-induced peripheral sensitization in vitro is nontrivial and will require careful selection of mediators and/or more complex, longitudinal multicellular setups. Especially in the latter, our novel GCamP6f-induced pluripotent stem cell line may be of value.

AB - Peripheral sensitization of nociceptors is believed to be a key driver of chronic pain states. Here, we sought to study the effects of a modified version of inflammatory soup on the excitability of human stem cell-derived sensory neurons. For this, we used a preexisting and a novel stem cell line, modified to stably express the calcium sensor GCamP6f. Upon treatment with inflammatory soup, we observed no changes in neuronal transcription or functional responses upon calcium imaging and only a very minor increase in resting membrane potential (RMP) via whole cell patch clamping: control RMP (-71.31 ± 1.1 mV) vs inflammatory soup RMP (-67.74 ± 1.29 mV), uncorrected 2-tailed independent samples t test, P = 0.0383. Similarly, small changes were observed when treating mouse primary sensory neurons with inflammatory soup. A semi-systematic reexamination of past literature further indicated that observed effects of inflammatory mediators on dissociated sensory neuron cultures are generally small. We conclude that modelling inflammation-induced peripheral sensitization in vitro is nontrivial and will require careful selection of mediators and/or more complex, longitudinal multicellular setups. Especially in the latter, our novel GCamP6f-induced pluripotent stem cell line may be of value.

UR - http://www.scopus.com/inward/record.url?scp=105000487335&partnerID=8YFLogxK

U2 - 10.1097/j.pain.0000000000003512

DO - 10.1097/j.pain.0000000000003512

M3 - Article

C2 - 40009350

SN - 0304-3959

JO - Pain

JF - Pain

ER -