Dexmedetomidine inhibits the NF-κB pathway and NLRP3 inflammasome to attenuate papain-induced osteoarthritis in rats.

Dexmedetomidine (Dex) has been reported to have an anti-inflammatory effect. However, its role on osteoarthritis (OA) has not been explored. This study investigates the effect of Dex on OA rat model induced by papain.

Sonic hedgehog signaling in spinal cord contributes to morphine-induced hyperalgesia and tolerance through upregulating brain-derived neurotrophic factor expression.

Purpose: Preventing opioid-induced hyperalgesia and tolerance continues to be a major clinical challenge, and the underlying mechanisms of hyperalgesia and tolerance remain elusive. Here, we investigated the role of sonic hedgehog (Shh) signaling in opioid-induced hyperalgesia and tolerance.

Methods: Shh signaling expression, behavioral changes, and neurochemical alterations induced by morphine were analyzed in male adult CD-1 mice with repeated administration of morphine.

Hedgehog signaling contributes to bone cancer pain by regulating sensory neuron excitability in rats.

Treating bone cancer pain continues to be a clinical challenge and underlying mechanisms of bone cancer pain remain elusive. Here, we reported that sonic hedgehog signaling plays a critical role in the development of bone cancer pain. Tibia bone cavity tumor cell implantation produces bone cancer-related mechanical allodynia, thermal hyperalgesia, and spontaneous and movement-evoked pain behaviors.

Electrical peripheral nerve stimulation relieves bone cancer pain by inducing Arc protein expression in the spinal cord dorsal horn.

Objective: The analgesic effect on chronic pain of peripheral nerve stimulation (PNS) has been proven, but its underlying mechanism remains unknown. Therefore, this study aimed to assess the analgesic effect of PNS on bone cancer pain in a rat model and to explore the underlying mechanism.

Materials And Methods: PNS on sciatic nerves with bipolar electrode was performed in both naïve and bone cancer pain model rats.

IL-18 Contributes to Bone Cancer Pain by Regulating Glia Cells and Neuron Interaction.

Unlabelled: Glial cell hyperactivity has been proposed to be responsible for chronic pain, however, the mechanisms remain unclear. Interleukin (IL)-18, released from glial cells, has been reported to be involved in neuropathic pain. In this study, we investigated the role of IL-18 in bone cancer pain.

Levo-Tetrahydropalmatine Attenuates Bone Cancer Pain by Inhibiting Microglial Cells Activation.

Objective: The present study is to investigate the analgesic roles of L-THP in rats with bone cancer pain caused by tumor cell implantation (TCI).

Methods: Thermal hyperalgesia and mechanical allodynia were measured at different time points before and after operation. L-THP (20, 40, and 60 mg/kg) were administrated intragastrically at early phase of postoperation (before pain appearance) and later phase of postoperation (after pain appearance), respectively.

Wnt/Ryk signaling contributes to neuropathic pain by regulating sensory neuron excitability and spinal synaptic plasticity in rats.

Treating neuropathic pain continues to be a major clinical challenge and underlying mechanisms of neuropathic pain remain elusive. We have recently demonstrated that Wnt signaling, which is important in developmental processes of the nervous systems, plays critical roles in the development of neuropathic pain through the β-catenin-dependent pathway in the spinal cord and the β-catenin-independent pathway in primary sensory neurons after nerve injury. Here, we report that Wnt signaling may contribute to neuropathic pain through the atypical Wnt/Ryk signaling pathway in rats.

Activation of the cAMP-PKA signaling pathway in rat dorsal root ganglion and spinal cord contributes toward induction and maintenance of bone cancer pain.

The objective of this study was to explore the role of cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) signaling in the development of bone cancer pain in rats. Female Sprague-Dawley rats (N=48) were divided randomly into four groups: sham (n=8), tumor cell implantation (TCI) (n=16), TCI+saline (n=8), and TCI+PKA inhibitor (n=16). Bone cancer-induced pain behaviors - thermal hyperalgesia and mechanical allodynia - were tested at postoperative days -3, -1, 1, 3, 5, 7, 10, and 14.

cGMP and cGMP-dependent protein kinase I pathway in dorsal root ganglia contributes to bone cancer pain in rats.

Study Design: A prospective, randomized experimental research.

Objective: To demonstrate the role of cGMP (cyclic guanosine monophosphate)-cGKI (cGMP-dependent protein kinase I) pathway in dorsal root ganglia (DRG) in bone cancer pain.

Summary Of Background Data: Treating bone cancer pain continues to possess a major clinical challenge because the specific cellular and molecular mechanisms underlying bone cancer pain remain elusive.

EphrinB-EphB receptor signaling contributes to bone cancer pain via Toll-like receptor and proinflammatory cytokines in rat spinal cord.

Treating bone cancer pain poses a major clinical challenge, and the mechanisms underlying bone cancer pain remain elusive. EphrinB-EphB receptor signaling may contribute to bone cancer pain through N-methyl-d-aspartate receptor neuronal mechanisms. Here, we report that ephrinB-EphB signaling may also act through a Toll-like receptor 4 (TLR4)-glial cell mechanism in the spinal cord.

Electrical nerve stimulation and the relief of chronic pain through regulation of the accumulation of synaptic Arc protein.

Electrical nerve stimulation (ENS) is used in clinical settings for the treatment of chronic pain, but the mechanism underlying its effects remains unknown. ENS has been found to mimic neural activity, inducing the accumulation of Arc in synapses. Activity-dependent synaptic accumulation of Arc protein has been shown to reduce synaptic strength by promoting endocytosis of the AMPA receptors in the synaptic membrane.

WNT signaling underlies the pathogenesis of neuropathic pain in rodents.

Treating neuropathic pain is a major clinical challenge, and the underlying mechanisms of neuropathic pain remain elusive. We hypothesized that neuropathic pain-inducing nerve injury may elicit neuronal alterations that recapitulate events that occur during development. Here, we report that WNT signaling, which is important in developmental processes of the nervous system, plays a critical role in neuropathic pain after sciatic nerve injury and bone cancer in rodents.

Reopening of ATP-sensitive potassium channels reduces neuropathic pain and regulates astroglial gap junctions in the rat spinal cord.

Adenosine triphosphate-sensitive potassium (K(ATP)) channels are suggested to be involved in pathogenesis of neuropathic pain, but remain underinvestigated in primary afferents and in the spinal cord. We examined alterations of K(ATP) channels in rat spinal cord and tested whether and how they could contribute to neuropathic pain. The results showed that protein expression for K(ATP) channel subunits SUR1, SUR2, and Kir6.

Blocking EphB1 receptor forward signaling in spinal cord relieves bone cancer pain and rescues analgesic effect of morphine treatment in rodents.

Treating bone cancer pain continues to be a clinical challenge and underlying mechanisms of bone cancer pain remain elusive. Here, we report that EphB1 receptor forward signaling in the spinal cord is critical to the development of bone cancer pain and morphine tolerance in treating bone cancer pain. Tibia bone cavity tumor cell implantation (TCI) produces bone cancer-related thermal hyperalgesia, mechanical allodynia, spontaneous and movement-evoked pain behaviors, and bone destruction.

Spinal matrix metalloproteinase-9 contributes to physical dependence on morphine in mice.

Preventing and reversing opioid dependence continues to be a clinical challenge and underlying mechanisms of opioid actions remain elusive. We report that matrix metalloproteinase-9 (MMP-9) in the spinal cord contributes to development of physical dependence on morphine. Chronic morphine exposure and naloxone-precipitated withdrawal increase activity of spinal MMP-9.

EphrinBs/EphBs signaling is involved in modulation of spinal nociceptive processing through a mitogen-activated protein kinases-dependent mechanism.

Background: Our previous studies have demonstrated that EphBs receptors and ephrinBs ligands were involved in modulation of spinal nociceptive information. However, the downstream mechanisms that control this process are not well understood. The aim of this study was to further investigate whether mitogen-activated protein kinases (MAPKs), as the downstream effectors, participate in modulation of spinal nociceptive information related to ephrinBs/EphBs.