Cav3 channels play an important role in modulating chronic pain. However, less is known about the functional changes of Cav3 channels in superficial spinal dorsal horn in neuropathic pain states. Here, we examined the effect of partial sciatic nerve ligation (PSNL) on either expression or electrophysiological properties of Cav3 channels in superficial spinal dorsal horn. Our in vivo studies showed that the blockers of Cav3 channels robustly alleviated PSNL-induced mechanical allodynia and thermal hyperalgesia, which lasted at least 14 days following PSNL. Meanwhile, PSNL triggered an increase in both mRNA and protein levels of Cav3.2 but not Cav3.1 or Cav3.3 in rats. However, in Cav3.2 knockout mice, PSNL predominantly attenuated mechanical allodynia but not thermal hyperalgesia. In addition, the results of whole-cell patch-clamp recordings showed that both the overall proportion of Cav3 current-expressing neurons and the Cav3 current density in individual neurons were elevated in spinal lamina II neurons from PSNL rats, which could not be recapitulated in Cav3.2 knockout mice. Altogether, our findings reveal that the elevated functional Cav3.2 channels in superficial spinal dorsal horn may contribute to the mechanical allodynia in PSNL-induced neuropathic pain model.
The tumor suppressor p53 plays a crucial role in embryonic neuron development and neurite growth, and its involvement in neuronal homeostasis has been proposed. To better understand how the lack of the p53 gene function affects neuronal activity, spine development, and plasticity, we examined the electrophysiological and morphological properties of layer 5 (L5) pyramidal neurons in the primary somatosensory cortex barrel field (S1BF) by using in vitro whole-cell patch clamp and in vivo two-photon imaging techniques in p53 knockout (KO) mice. We found that the spiking frequency, excitatory inputs, and sag ratio were decreased in L5 pyramidal neurons of p53KO mice. In addition, both in vitro and in vivo morphological analyses demonstrated that dendritic spine density in the apical tuft is decreased in L5 pyramidal neurons of p53KO mice. Furthermore, chronic imaging showed that p53 deletion decreased dendritic spine turnover in steady-state conditions, and prevented the increase in spine turnover associated with whisker stimulation seen in wildtype mice. In addition, the sensitivity of whisker-dependent texture discrimination was impaired in p53KO mice compared with wildtype controls. Together, these results suggest that p53 plays an important role in regulating synaptic plasticity by reducing neuronal excitability and the number of excitatory synapses in S1BF.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.