Abstract
—Neuropathic pain (NP) treatment remains a challenge because the pathomechanism is not yet fully understood. Because of low treatment efficacy, there is an important unmet need in neuropathic pain patients, and the development of a more effective pharmacotherapy is urgently required. Neuroinflammation induced by oxidative stress-mediated activation of nuclear factor-kappa B (NF-κB) plays an important role in NP. In this study, we aimed to investigate the protective properties of tetrahydropalmatine (THP) on a spared nerve injury (SNI) model of neuropathic pain in mice in in vivo and also in in vitro experiments. THP decreased mechanical hyperalgesia and cold allodynia compared with the SNI group. A microarray was applied to analyze differentially expressed of mRNA among different groups, and THP noticeably changed the expression of MAPK-related proteins compared with the SNI groups. H&E staining showed that the THP changed the inflammation after the spared nerve injury, with decreased NO expression in the THP group as compared to the SNI group. In addition, SNI-induced pain was reversed by intraperitoneal administration of THP, and further results indicated that THP suppressed inducible nitric oxide synthase (iNOS, pro-nociceptive mediators), phosphorylated MAPKs, and p65 in the dorsal root ganglions and sciatic nerve, while the serum levels of the pro-inflammatory cytokines IL-1β were significantly higher in the SNI group as compared to the THP group. To identify the molecular mechanism of the antineuropathic activity of THP, sodium nitroprusside (SNP)-induced neuro-2a (N2a) cells, LPS-induced BV2 cells, and LTA-induced astrocytes were further investigated in signaling pathways. In vitro experiments indicated that THP suppressed the expression of IL-1β, iNOS, phosphorylated MAPKs, and p65, which were assayed using western blotting, and immunofluorescence.
Highlights
Neuropathic pain (NP) is one type of pain caused by a lesion or disease of the somatosensory system and can severely affects the quality of life of patients [1]
The mechanical hyperalgesia and cold allodynia behaviors of each group were detected, and there was a decrease in mechanical withdrawal thresholds (MWT) and cold allodynia in the ipsilateral paw from 3 to 14 days after spared nerve injury (SNI) compared to the sham-operated mice
The results showed that THP decreased the expression of nitric oxide (NO) in the SNI-induced pain model, and the expression of IL-1β in serum was decreased in the SNI + THP and SNI + SMT groups compared with the SNI group (Fig. 5a–e)
Summary
Neuropathic pain (NP) is one type of pain caused by a lesion or disease of the somatosensory system and can severely affects the quality of life of patients [1]. The commonly used clinical treatment methods include local nerve block, sympathetic block, physiotherapy, opioid anesthetics, anti-infective agents, antidepressants, and/or anxiolytics. These drugs are addictive, but they have certain unwanted side effects [2, 3], and pain management remains a challenge with their continued use. Current studies have shown that the various biological activities of tetrahydropalmatine (THP) are the inhibition of calcium overload and anti-inflammatory and antiarrhythmic action, while few studies have been conducted to explore its role in spared nerve injury (SNI)-induced neuropathic pain. The aim of this study is to verify the mechanism used by THP to alleviate SNI-induced neuropathic pain and neuroinflammation
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