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Papers of the Week

Papers: 27 May 2023 - 2 Jun 2023

Basic Science

Animal Studies, Molecular/Cellular, Neurobiology

Neuropathic Pain

2023 May 19





Involvement of Mrgprd-expressing nociceptors-recruited spinal mechanisms in nerve injury-induced mechanical allodynia.


Wang L, Su X, Yan J, Wu Q, Xu X, Wang X, Liu X, Song X, Zhang Z, Hu W, Liu X, Zhang Y


Mechanical allodynia and hyperalgesia are intractable symptoms lacking effective clinical treatments in patients with neuropathic pain. However, whether and how mechanically responsive non-peptidergic nociceptors are involved remains elusive. Here, we showed that von Frey-evoked static allodynia and aversion, along with mechanical hyperalgesia after spared nerve injury (SNI) were reduced by ablation of -marked neurons. Electrophysiological recordings revealed that SNI-opened Aβ-fiber inputs to laminae I-II and II, as well as C-fiber inputs to II, were all attenuated in Mrgprd-ablated mice. In addition, priming chemogenetic or optogenetic activation of Mrgprd neurons drove mechanical allodynia and aversion to low-threshold mechanical stimuli, along with mechanical hyperalgesia. Mechanistically, gated Aβ and C inputs to II were opened, potentially via central sensitization by dampening potassium currents. Altogether, we uncovered the involvement of Mrgprd nociceptors in nerve injury-induced mechanical pain and dissected the underlying spinal mechanisms, thus providing insights into potential therapeutic targets for pain management.