Proanthocyanidins Induce Analgesic and Anxiolytic Effects in Spared Nerve Injured Mice by Decreasing Firing Rate of Pyramidal Cells in the Insular Cortex

Overview

Journal Front Mol Neurosci

Specialty Molecular Biology

Date 2023 Jul 10

PMID 37426072

Authors

Pan Wang

Hua-Xing Si

Da-Yu Zhu

Ke-Ke Xing

Jian Wang

Ting-Ting Cao

Han Zhao

Xiao-Die Liu

Ming-Ming Zhang

Tao Chen

Affiliations

Soon will be listed here.

Abstract

Neuropathic pain is one of the most common symptoms of clinical pain that often accompanied by severe emotional changes such as anxiety. However, the treatment for comorbidity of chronic pain and anxiety is limited. Proanthocyanidins (PACs), a group of polyphenols enriched in plants and foods, have been reported to cause pain-alleviating effects. However, whether and how PACs induce analgesic and anxiolytic effects in the central nervous system remain obscure. In the present study, we observed that microinjection of PACs into the insular cortex (IC) inhibited mechanical and spontaneous pain sensitivity and anxiety-like behaviors in mice with spared nerve injury. Meanwhile, PACs application exclusively reduced the FOS expression in the pyramidal cells but not interneurons in the IC. electrophysiological recording of the IC further showed that PACS application inhibited the firing rate of spikes of pyramidal cells of IC in neuropathic pain mice. In summary, PACs induce analgesic and anxiolytic effects by inhibiting the spiking of pyramidal cells of the IC in mice with neuropathic pain, which should provide new evidence of PACs as the potential clinical treatment of chronic pain and anxiety comorbidity.

References

Fan H, Wu Z, Zhu D, Gu J, Xu M, Zhang M . Proanthocyanidins Inhibit the Transmission of Spinal Pain Information Through a Presynaptic Mechanism in a Mouse Inflammatory Pain Model. Front Neurosci. 2022; 15:804722. PMC: 8850919. DOI: 10.3389/fnins.2021.804722. View

Anhe F, Choi B, Dyck J, Schertzer J, Marette A . Host-Microbe Interplay in the Cardiometabolic Benefits of Dietary Polyphenols. Trends Endocrinol Metab. 2019; 30(6):384-395. DOI: 10.1016/j.tem.2019.04.002. View

Jasmin L, Rabkin S, Granato A, Boudah A, Ohara P . Analgesia and hyperalgesia from GABA-mediated modulation of the cerebral cortex. Nature. 2003; 424(6946):316-20. DOI: 10.1038/nature01808. View

Finnerup N, Kuner R, Jensen T . Neuropathic Pain: From Mechanisms to Treatment. Physiol Rev. 2020; 101(1):259-301. DOI: 10.1152/physrev.00045.2019. View

Gamal-Eltrabily M, Espinosa de Los Monteros-Zuniga A, Manzano-Garcia A, Martinez-Lorenzana G, Condes-Lara M, Gonzalez-Hernandez A . The Rostral Agranular Insular Cortex, a New Site of Oxytocin to Induce Antinociception. J Neurosci. 2020; 40(29):5669-5680. PMC: 7363465. DOI: 10.1523/JNEUROSCI.0962-20.2020. View

Kang S, Kwak C, Lee J, Sim S, Shim J, Choi T . Bidirectional modulation of hyperalgesia via the specific control of excitatory and inhibitory neuronal activity in the ACC. Mol Brain. 2015; 8(1):81. PMC: 4668615. DOI: 10.1186/s13041-015-0170-6. View

Duan B, Cheng L, Bourane S, Britz O, Padilla C, Garcia-Campmany L . Identification of spinal circuits transmitting and gating mechanical pain. Cell. 2014; 159(6):1417-1432. PMC: 4258511. DOI: 10.1016/j.cell.2014.11.003. View

Jiang X, Liu J, Lin Q, Mao K, Tian F, Jing C . Proanthocyanidin prevents lipopolysaccharide-induced depressive-like behavior in mice via neuroinflammatory pathway. Brain Res Bull. 2017; 135:40-46. DOI: 10.1016/j.brainresbull.2017.09.010. View

Huang P, Xiang X, Chen X, Li H . Somatostatin Neurons Govern Theta Oscillations Induced by Salient Visual Signals. Cell Rep. 2020; 33(8):108415. DOI: 10.1016/j.celrep.2020.108415. View

10.

Hargreaves K, Dubner R, Brown F, Flores C, Joris J . A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain. 1988; 32(1):77-88. DOI: 10.1016/0304-3959(88)90026-7. View

11.

Zhang M, Liu S, Chen T, Koga K, Zhang T, Li Y . Effects of NB001 and gabapentin on irritable bowel syndrome-induced behavioral anxiety and spontaneous pain. Mol Brain. 2014; 7:47. PMC: 4071154. DOI: 10.1186/1756-6606-7-47. View

12.

Pan C, Wang C, Zhang L, Song L, Chen Y, Liu B . Procyanidins attenuate neuropathic pain by suppressing matrix metalloproteinase-9/2. J Neuroinflammation. 2018; 15(1):187. PMC: 6013948. DOI: 10.1186/s12974-018-1182-9. View

13.

Tremblay R, Lee S, Rudy B . GABAergic Interneurons in the Neocortex: From Cellular Properties to Circuits. Neuron. 2016; 91(2):260-92. PMC: 4980915. DOI: 10.1016/j.neuron.2016.06.033. View

14.

Del Rio D, Borges G, Crozier A . Berry flavonoids and phenolics: bioavailability and evidence of protective effects. Br J Nutr. 2010; 104 Suppl 3:S67-90. DOI: 10.1017/S0007114510003958. View

15.

Niwano Y, Kohzaki H, Shirato M, Shishido S, Nakamura K . Metabolic Fate of Orally Ingested Proanthocyanidins through the Digestive Tract. Antioxidants (Basel). 2023; 12(1). PMC: 9854439. DOI: 10.3390/antiox12010017. View

16.

Lee J, Chen Q, Zhuo M . Synaptic Plasticity in the Pain-Related Cingulate and Insular Cortex. Biomedicines. 2022; 10(11). PMC: 9687873. DOI: 10.3390/biomedicines10112745. View

17.

Hua R, Wang X, Chen X, Wang X, Huang P, Li P . Calretinin Neurons in the Midline Thalamus Modulate Starvation-Induced Arousal. Curr Biol. 2018; 28(24):3948-3959.e4. DOI: 10.1016/j.cub.2018.11.020. View

18.

Zhu D, Cao T, Fan H, Zhang M, Duan H, Li J . The increased in vivo firing of pyramidal cells but not interneurons in the anterior cingulate cortex after neuropathic pain. Mol Brain. 2022; 15(1):12. PMC: 8800281. DOI: 10.1186/s13041-022-00897-9. View

19.

Erdo F, Bors L, Farkas D, Bajza A, Gizurarson S . Evaluation of intranasal delivery route of drug administration for brain targeting. Brain Res Bull. 2018; 143:155-170. DOI: 10.1016/j.brainresbull.2018.10.009. View

20.

Apkarian A, Bushnell M, Treede R, Zubieta J . Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain. 2005; 9(4):463-84. DOI: 10.1016/j.ejpain.2004.11.001. View