Objective To explore the role of pyramidal neurons of ventromedial prefrontal cortex (vmPFC) in pain and anxiety-like behavior of spared nerve injury (SNI) mice. Methods Spared nerve injury (SNI) was used to mimic neuropathic pain (NP) animal model, while a same incision without nerve injury was performed to establish the sham control group. Kainic aicd, normal saline, AAV2/9 virus were intracranially injected into contralateral vmPFC of SNI mice. Von frey filaments were used to detect the paw withdraw threshold (PWT) of the ipsilateral planta of SNI mice. The elevated plus maze (EPM) was used to assess anxiety behaviors of SNI mice. Immunofluorescence staining was used to observe the expression of c-fos, the neuronal loss and the astrocytic activation in the contralateral vmPFC. RNA-scope and immunofluorescence staining were used to identify the neuronal type of c-fos positive neuron of vmPFC. Results Compared with sham mice, ipsilateral PWT, entries in open arms and cumulative duration in open arms of SNI mice were significantly decreased at 7d and 14d after SNI (P<0.05). Compared with sham mice, c-fos positive neurons were significantly increased in the contralateral of vmPFC of SNI mice (P<0.05). In addition, the c-fos positive neurons were almost Vglut1 positive neurons. Compared with the SNI mice which intracranially injected into contraleral vmPFC with normal saline, ipsilateral PWT, entries in open arms and cumulative duration in open arms of the SNI mice which intracranially injected into contraleral vmPFC with kainic acid were increased (P<0.05). Meanwhile, the SNI mice which intracranially injected into contraleral vmPFC with kainic acid exhibited obvious neuronal loss and astrocytic activation in the contralateral vmPFC. In addition, using chemogenetics strategy to inhibit the pyramidal neurons in contralateral vmPFC of SNI mice, the c-fos positive neurons were significantly deceased, the ipsilateral PWT, entries in open arms and cumulative duration in open arms were significantly increased (P<0.05). Conclusions Pyramidal neurons in the contralateral vmPFC may be involved in the development of pain and anxiety-like behaviors of SNI mice.
Key words
Ventromedial prefrontal cortex; /
/
Chemogenetics; /
/
Pyramidal neuron; /
/
Pain; /
/
Anxiety
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
References
[1] 杜涛, 袁文茜, 曹伯旭, 等. 慢性神经病理性疼痛[J]. 中国疼痛医学杂志, 2021, 27(7): 481-485. DIO: 10.3969/j.issn.1006-9852.2021.07.001.
[2] Li KL, Chen YM, Wang XQ, et al. Bibliometric analysis of studies on neuropathic pain associated with depression or anxiety published from 2000 to 2020[J]. Front Hum Neurosci, 2021, 15: 729587. DOI: 10.3389/fnhum.2021.729587.
[3] Kim D, Mirmina J, Narine S, et al. Altered physical pain processing in different psychiatric conditions[J]. Neurosci Biobehav Rev, 2022, 133: 104510. DOI: 10.1016/j.neubiorev.2021.12.033.
[4] Jalbrzikowski M, Larsen B, Hallquist M, et al. Development of white matter microstructure and intrinsic functional connectivity between the amygdala and ventromedial prefrontal cortex: associations with anxiety and depression[J]. Biol Psychiatry, 2017, 82(7): 511-521. DOI: 10.1016/j.biop syc h.2017.01.008.
[5] Baliki MN, Petre B, Torbey S, et al. Corticostriatal functional connectivity predicts transition to chronic back pain[J]. Nat Neurosci, 2012, 15(8): 1117-1119. DOI: 10.1038/nn.3153.
[6] Metz AE, Yau HJ, Centeno MV, et al. Morphological and functional reorganization of rat medial prefrontal cortex in neuropathic pain[J]. Proc Natl Acad Sci U S A, 2009, 106(7): 2423-2428. DOI: 10.1073/pnas.0809897106.
[7] Nawreen N, Baccei ML, Herman JP. Single prolonged stress reduces intrinsic excitability and excitatory synaptic drive onto pyramidal neurons in the infralimbic prefrontal cortex of adult male rats[J]. Front Cell Neurosci, 2021, 15: 705660. DOI: 10.3389/fncel.2021.705660.
[8] Liang HY, Chen ZJ, Xiao H, et al. nNOS-expressing neurons in the vmPFC transform pPVT-derived chronic pain signals into anxiety behaviors[J]. Nat Commun, 2020, 11(1): 2501. DOI: 10.1038/s41467-020-16198-5.
[9] Decosterd I, Woolf CJ. Spared nerve injury: an animal model of persistent peripheral neuropathic pain[J]. Pain, 2000, 87(2): 149-158. DOI: 10.1016/S0304-3959(00)00276-1.
[10]Pak DJ, Yong RJ, Kaye AD, et al. Chronification of pain: mechanisms, current understanding, and clinical implications[J]. Curr Pain Headache Rep, 2018, 22(2): 9. DOI: 10.1007/s11916-018-0666-8.
[11]Huang J, Gadotti V, Chen L, et al. A neuronal circuit for activating descending modulation of neuropathic pain[J]. Nat Neurosci, 2019, 22(10): 1659-1668. DOI: 10.1038/s41593-019-0481-5.
[12]Bushnell M, Ceko M, Low L. Cognitive and emotional control of pain and its disruption in chronic pain[J]. Nat Rev Neurosci, 2013, 14(7): 502-511. DOI: 10.1038/nrn3516.
[13]Hiser J, Koenigs M. The multifaceted role of the ventromedial prefrontal cortex in emotion, decision making, social cognition, and psychopathology[J]. Biol Psychiatry, 2018, 83(8): 638-647. DOI: 10.1016/j.biopsych.2017.10.030.
[14]Yin J, Liang S, Li F, et al. dmPFC-vlPAG projection neurons contribute to pain threshold maintenance and antianxiety behaviors[J]. J Clin Invest, 2020, 130(12): 6555-6570. DOI: 10.1172/JCI127607.
[15]许祥影, 沈晶晶, 朱贺, 等. 硫辛酸对炎性痛小鼠脊髓背角c-Fos和Iba-1的影响[J]. 中国疼痛医学杂志, 2019, 25(9): 655-659, 665. DOI: 10.3969/j.issn.1006-9852.2019.09.004.
[16]宿世玉, 田恩琪, 党秀静, 等. 触液核在大鼠慢性瘙痒维持中的作用[J]. 中华麻醉学杂志, 2013, 33(7): 807-809. DOI: 10.3760/cma.j.issn.0254-1416.2013.07.007.
[17]Bi LL, Wang J, Luo ZY, et al. Enhanced excitability in the infralimbic cortex produces anxiety-like behaviors[J]. Neuropharmacology, 2013, 72: 148-156. DOI: 10.1016/j.neuropharm.2013.04.048.
[18]Felix-Ortiz AC, Beyeler A, Seo C, et al. BLA to vHPC inputs modulate anxiety-related behaviors[J]. Neuron, 2013, 79(4): 658-664. DOI: 10.1016/j.neuron.2013.06.016.
[19]Visser E, Matos MR, Mitrić MM, et al. Extinction of cocaine memory depends on a feed-forward inhibition circuit within the medial prefrontal cortex[J]. Biol Psychiatry, 2022, 91(12): 1029-1038. DOI: 10.1016/j.biopsych.2021.08.008.
PDF(12494 KB)
