Abstract
Neuropathic pain is a serious clinical problem that is difficult to treat. Purinoceptors (P2Rs) transduce pain perception from the peripheral to the central nervous system and play an important role in the transmission of neuropathic pain signals. We previously found that the crude extracts of Hericium erinaceus mycelium (HE-CE) inhibited P2R-mediated signaling in cells and reduced heat-induced pain in mice. The present study explored the effects of HE-CE on neuropathic pain. We used adenosine triphosphate (ATP) as a P2R agonist to generate Ca2+ signaling and neuronal damage in a cell line. We also established a neuropathic mouse model of L5 spinal nerve ligation (L5-SNL) to examine neuropathic pain and neuroinflammation. Neuropathic pain was recorded using the von Frey test. Neuroinflammation was evaluated based on immunohistofluorescence observation of glial fibrillary acidic protein (GFAP) levels in astrocytes, ionized calcium-binding adaptor molecule1 (iba1) levels in microglia, and IL-6 levels in plasma. The results show that HE-CE and erinacine-S, but not erinacine-A, totally counteracted Ca2+ signaling and cytotoxic effects upon P2R stimulation by ATP in human osteosarcoma HOS cells and human neuroblastoma SH-SY5Y cells, respectively. SNL induced a decrease in the withdrawal pressure of the ipsilateral hind paw, indicating neuropathic pain. It also raised the GFAP level in astrocytes, the iba1 level in microglia, and the IL-6 level in plasma, indicating neuroinflammation. HE-CE significantly counteracted the SNL-induced decrease in withdrawal pressure, illustrating that it could relieve neuropathic pain. It also reduced SNL-induced increases in astrocyte GFAP levels, microglial iba1 levels, and plasma IL-6 levels, suggesting that HE-CE reduces neuroinflammation. Erinacine-S relieved neuropathic pain better than HE-CE. The present study demonstrated that HE inhibits P2R and, thus, that it can relieve neuropathic pain and neuroinflammation.
Highlights
Pain is a sensation triggered in the nervous system in response to the stimulation of the purinoceptor (P2R) by adenosine triphosphate (ATP)
Spinal nerve ligation (SNL) surgery causes neuropathic pain by inflicting neuronal damage on the dorsal root ganglion, which increases mechanical allodynia. e von Frey tests in the present study showed that Hericium erinaceus mycelium (HE-CE) significantly suppresses SNL-induced allodynia, characterizing HE-CE as an analgesic
We previously reported that HE-CE inhibited P2Rcoupled Ca2+ signaling and heat-induced pain [21]. e current study showed that HE-CE and E-S can completely inhibit the ATP-induced rise in [Ca2+]c in human osteosarcoma (HOS) cells expressing the P2R subtypes P2X1,4,5,6,7R and P2Y2,4,5,9,11R
Summary
Pain is a sensation triggered in the nervous system in response to the stimulation of the purinoceptor (P2R) by adenosine triphosphate (ATP). Abundant evidence suggests that P2Rs are important in the transmission of neuropathic pain [7,8], which is the most debilitating of all clinical pain syndromes Such pain results from nerve injury due to surgery, diabetes, cancer, or infection in the central or peripheral nervous system [9]. Us, safe and effective treatments for relieving neuropathic pain are urgently needed In this regard, P2R antagonists protect against neuropathic pain [10] and may guide the search for analgesic medicine in patients with neuropathic pain. E surgery leads to immediate postoperative pain and results in prolonged mechanical allodynia As such, it may be a good model for studying neuropathic pain. We explored mechanical allodynia, activation of spinal astrocytes and microglia, and plasma IL-6 levels following SNL surgery, seeking to better understand the progression of neuropathic pain. Erinacine-A (E-A), a cyanthin diterpenoid, and erinacine-S (E-S), a sesterterpene, are two major components of HE-CE [22,23,24,25]. e present study investigated the inhibitory effects of HE-CE, E-A, and E-S on P2R signaling, as well as whether these substances can relieve SNL-induced neuropathic pain and neuroinflammation
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