Articles: rat.
-
Chronic post-thoracotomy pain (CPTP) is characterized by high incidence, long duration, and severity of pain. Medial prefrontal cortex (mPFC) is a brain region closely associated with chronic pain, and norepinephrine is involved in pain regulation. But the role of mPFC norepinephrine in CPTP and its possible mechanism is unclear. ⋯ Inhibition of norepinephrine in contralateral mPFC after thoracotomy improved CPTP. The potential mechanisms may include rescuing the expression of AQP4 and IL-33, as well as reducing neuroinflammation and Bdkrb2 expression.
-
Methotrexate (MTX) is an agent used in the treatment of many neoplastic and non-neoplastic diseases and is known to cause oxidative damage in normal tissues. Curcumin (Cur) is a natural polyphenol compound with powerful antioxidant and antiapoptotic effects. In this study we investigate the effects of Cur on MTX-induced ovarian damage. ⋯ Cur pretreatment prior to MTX administration may be an effective option in preserving the ovarian follicle pool by regulating P53 and PARP-1 expressions with its antioxidant effect.
-
Treating bone cancer pain (BCP) continues to be a clinical challenge, and the underlying mechanisms of BCP remain elusive. This study reports that Wnt5a/Ryk signaling in the dorsal root ganglion neurons is critical to the development of BCP. Tibia bone cavity tumor cell implantation produces spontaneous and evoked behaviorally expressed pain as well as ectopic sprouting and activity of Wnt5a/Ryk signaling in the neural soma and peripheral terminals and the tumor-affected bone tissues. ⋯ Blocking Ryk receptor activation suppresses Wnt5a-induced mechanical allodynia and thermal hyperalgesia. Wnt5a facilitation of transient receptors potential vanilloid type-1 sensitization is blocked by inhibiting c-Jun N-terminal kinase activation. These findings indicate a critical peripheral mechanism of Wnt5a/Ryk signaling underlying the pathogenesis of BCP and suggest that targeting Wnt5a/Ryk in the primary sensory neurons and the tumor-invasive area may be an effective approach for the prevention and treatment of BCP.
-
Fentanyl is a synthetic opioid that is widely used in anesthesiology, but its illicit use is rapidly increasing. At high doses, fentanyl induces unconsciousness and muscle rigidity, the mechanisms of which are poorly understood. Since animal models are needed to study these effects, the aim of this study was to establish a rat model of fentanyl abuse and investigate the effects of repeated high-dose fentanyl injections on loss of righting reflex, heart rate, respiratory depression, muscle, and brain activity. ⋯ The authors established a rodent model of repeated high-dose fentanyl administration. Overall, significant evidence of tolerance was not observed after 10 exposures of high-dose fentanyl for any of the analyzed parameters. These results suggest that tolerance does not develop for fentanyl-induced unconsciousness, muscle rigidity, or respiratory depression.
-
High molecular weight hyaluronan (HMWH) inhibits hyperalgesia induced by diverse pronociceptive inflammatory mediators and their second messengers, in rats of both sexes. However, the hyperalgesia induced by ligands at 3 pattern recognition receptors, lipopolysaccharide (a toll-like receptor 4 agonist), lipoteichoic acid (a toll-like receptor 2/6 agonist), and nigericin (a NOD-like receptor family, pyrin domain containing 3 activator), and oxaliplatin and paclitaxel chemotherapy-induced peripheral neuropathy are only attenuated in males. After gonadectomy or intrathecal administration of an antisense to G-protein-coupled estrogen receptor 30 (GPER) mRNA, HMWH produces antihyperalgesia in females. ⋯ In females, hyperalgesia induced by PKCε agonist, ψεRACK, in control but not in primed nociceptors, was inhibited by HMWH. Inhibitors of 2 GPER second messengers, extracellular-regulated kinase 1/2 and nonreceptor tyrosine kinase, also unmasked HMWH antihyperalgesia in females with oxaliplatin chemotherapy-induced peripheral neuropathy, a condition in which nociceptors are primed as well as sensitized. Our results support GPER-dependent sex dimorphism in HMWH-induced antihyperalgesia for pain induced by pattern recognition receptor agonists, and chronic inflammatory and neuropathic pain, mediated by changes in signaling downstream of PKCε in primed nociceptors.