Proanthocyanidins Inhibit the Transmission of Spinal Pain Information Through a Presynaptic Mechanism in a Mouse Inflammatory Pain Model.

Hongwei Fan,Mang Xu,Zhenyu Wu,Dayu Zhu,Tao Chen,Haokai Duan,Yunqing Li,Junxiang Gu,Mingzhe Zhang

doi:10.3389/fnins.2021.804722

Abstract

Inflammatory pain is one of the most common symptoms of clinical pain that seriously affects patient quality of life, but it currently has limited therapeutic options. Proanthocyanidins, a group of polyphenols enriched in plants and foods, have been reported to exert anti-inflammatory pain-alleviating effects. However, the mechanism by which proanthocyanidins relieve inflammatory pain in the central nervous system is unclear. In the present study, we observed that intrathecal injection of proanthocyanidins inhibited mechanical and thermal pain sensitivity in mice with inflammatory pain induced by Complete Freund’s Adjuvant (CFA) injection. Electrophysiological results further showed that proanthocyanidins inhibited the frequency of spontaneous excitatory postsynaptic currents without affecting the spontaneous inhibitory postsynaptic currents or the intrinsic properties of parabrachial nucleus-projecting neurons in the spinal cord. The effect of proanthocyanidins may be mediated by their inhibition of phosphorylated activation of the PI3K/Akt/mTOR pathway molecules in dorsal root ganglia neurons. In summary, intrathecal injection of procyanidin induces an obvious anti-inflammatory pain effect in mice by inhibiting peripheral excitatory inputs to spinal neurons that send nociceptive information to supraspinal areas.

Highlights

Inflammatory pain is caused by chemical or physical stimulation of damaged tissue
We explored whether intrathecal (i.t.) injection of proanthocyanidins should change the mechanical and heat pain responses by testing the paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) in mice administered with Complete Freund’s Adjuvant (CFA) or saline injection
We found that the PWMT and PWTL of mice with left paw CFA (10 μl) injection were significantly lower than those of mice with the same amount of saline injection, indicating that mechanical allodynia and thermal hyperalgesia occurred in mice with CFA injection (P < 0.0001, n = 6 and 10 in the saline and CFA groups, respectively, unpaired t-test) (Figures 1A,B)

Summary

Introduction

Inflammatory pain is caused by chemical or physical stimulation of damaged tissue (surgery, osteoarthritis or trauma, etc.). Neurons that send nociceptive information to Proanthocyanidins Inhibit Inflammatory Pain supraspinal areas are primarily located in lamina I of the dorsal horn, 95% of which project to the parabrachial nucleus (PBN). Proanthocyanidins are oligomers or polymers composed of units of flavanols extracted from cherry, grape seeds, cocoa, and other plants (Chacón et al, 2009) Their protective effects in nervous system diseases have received increasing attention in recent years. Intra-articular injection of proanthocyanidins inhibits the expression of inflammasomes in macrophages and relieves arthritis (Liu et al, 2017) These results primarily indicate that proanthocyanidins have anti-inflammatory effects by acting on peripheral tissues. Pan et al (2018) reported that proanthocyanidins produce behavioral analgesia by inhibiting activated matrix metalloproteinase (MMP)-9 and MMP-2 in the spinal cord of mice with neuropathic pain, whether proanthocyanidins relieve inflammatory pain and the possible mechanism in regulating nociceptive information transmission in the central nervous system remain elusive

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Results

Conclusion