Pro-resolving mediator maresin 1 ameliorates pain hypersensitivity in a rat spinal nerve ligation model of neuropathic pain.

Background: Pro-resolving mediators (PRMs) are considered as emerging analgesics for chronic pain. Maresin 1 (MaR1) is a newly identified member of PRMs, and recent studies implicate its potential role in some pain conditions. As the function of MaR1 in neuropathic pain remains unclear, we investigated the effects of MaR1 on pain hypersensitivity and the underlying mechanism using a rat spinal nerve ligation (SNL) model of neuropathic pain.

Suppression of Pax2 Attenuates Allodynia and Hyperalgesia through ET-1-ETAR-NFAT5 Signaling in a Rat Model of Neuropathic Pain.

Endothelin-1 (ET-1) and its receptors (ETAR/ETBR) emerge to be a key signaling axis in neuropathic pain processing and are recognized as new therapeutic targets. Yet, little is known on the functional regulation of ET-1 axis during neuropathic pain. Bioinformatics analysis indicated that paired box gene 2 (Pax2) or nuclear factor of activated T-cells 5 (NFAT5), two transcription factors involved in the modulation of neurotransmission, may regulate ET-1.

Enriched Environment and Effects on Neuropathic Pain: Experimental Findings and Mechanisms.

Neuropathic pain inflicts tremendous biopsychosocial suffering for patients worldwide. However, safe and effective treatment of neuropathic pain is a prominent unmet clinical need. Environmental enrichment (EE) is an emerging cost-effective nonpharmacological approach to alleviate neuropathic pain and complement rehabilitation care.

Flurbiprofen axetil attenuates cerebral ischemia/reperfusion injury by reducing inflammation in a rat model of transient global cerebral ischemia/reperfusion.

Ischemic stroke has been ranked as the second cause of death in patients worldwide. Inflammation which is activated during cerebral ischemia/reperfusion (I/R) is an important mechanism leading to brain injury. The present study aimed to investigate the effect of flurbiprofen axetil on cerebral I/R injury and the role of inflammation in this process.

Histone deacetylase 5 (HDAC5) regulates neuropathic pain through SRY-related HMG-box 10 (SOX10)-dependent mechanism in mice.

A strong link between histone deacetylases (HDACs) and nociceptive hypersensitivity has been indicated in different pain models. However, the underlying molecular and cellular mechanisms remain elusive. Here, we discovered that partial sciatic nerve ligation-induced mechanical allodynia and thermal hyperalgesia in mice were associated with increased mRNA and protein expressions of HDAC5 (a member of class IIa HDACs) and SRY-related HMG-box 10 (SOX10) in the ipsilateral lumbar dorsal horn.

miRNA-23a/CXCR4 regulates neuropathic pain via directly targeting TXNIP/NLRP3 inflammasome axis.

Background: Chemokine CXC receptor 4 (CXCR4) in spinal glial cells has been implicated in neuropathic pain. However, the regulatory cascades of CXCR4 in neuropathic pain remain elusive. Here, we investigated the functional regulatory role of miRNAs in the pain process and its interplay with CXCR4 and its downstream signaling.

Targeted Overexpression of Astrocytic Endothelin-1 Attenuates Neuropathic Pain by Upregulating Spinal Excitatory Amino Acid Transporter-2.

We previously demonstrated that endogenous endothelin-1 (ET-1) inhibits pathological pain in a transgenic mouse model with astrocyte-specific ET-1 overexpression (GET-1 mice); however, the underlying mechanism is unclear. ET-1 regulates excitatory amino acid transporter-2 (EAAT-2), a predominant subtype of glutamate transporters that plays critical role in pain modulation in spinal astrocytes. We hypothesized that astrocytic ET-1 overexpression alleviates neuropathic pain through modulating EAAT-2.

Over-expression of astrocytic ET-1 attenuates neuropathic pain by inhibition of ERK1/2 and Akt(s) via activation of ETA receptor.

A differential role of endothelin-1 (ET-1) in pain processing has recently been suggested. However, the function of central ET-1 in neuropathic pain (NP) has not been fully elucidated to date. We report here the action of endogenous central ET-1 in sciatic nerve ligation-induced NP (SNL-NP) in a transgenic animal model that over-expresses ET-1 in the astrocytes (GET-1 mice).

Effects of repeated central administration of endothelin type A receptor antagonist on the development of neuropathic pain in rats.

Endothelin-1 (ET-1) predominates in the endothelin family effectively in vascular tone control, mitogenesis, and neuromodulation. Its receptors are widespread in the central nervous system (CNS) associated with endogenous pain control, suggesting an important role of ET-1 in central pain processing. This study aimed to evaluate the effect of central ET-1 on the development of neuropathic pain behaviour by repeated intrathecal administration of endothelin type A receptor (ETAR) antagonist (BQ-123) in a sciatic nerve ligation (SNL) animal model.

Over-expression of endothelin-1 in astrocytes, but not endothelial cells, ameliorates inflammatory pain response after formalin injection.

Aims: Endothelin-1 (ET-1) has been suggested to be involved in different types of pain due to its neuromodulatory nature. However, its role in inflammatory pain processing, specifically the origin-specific effect, has not yet been clearly defined. Therefore, the aim of this study is to determine the role of cell-type specific ET-1 induction in the modulation of inflammatory pain processing.