Articles: hyperalgesia.
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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.
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Minerva anestesiologica · Feb 2025
Effect of estazolam plus remimazolam on attenuating preoperative anxiety and remifentanil-induced postoperative hyperalgesia in elective gynecological laparoscopic surgery: a randomized clinical trial.
Preoperative anxiety is closely related to opioid-induced hyperalgesia, and high levels of preoperative anxiety have the potential to aggravate opioid-induced hyperalgesia. We aimed to estimate the effect of estazolam, remimazolam, and their combination on preoperative anxiety and opioid-induced hyperalgesia in patients undergoing elective gynecological laparoscopic surgery. ⋯ The preoperative application of estazolam, remimazolam, and their combination can relieve preoperative anxiety and postoperative pain for patients undergoing gynecological laparoscopic surgery. Moreover, the preoperative combination can also significantly reduce postoperative sufentanil consumption.
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The cerebrospinal fluid-contacting nucleus(CSF-contacting nucleus) is a pair of unique nuclei in the brain parenchyma which has long been demonstrated to play an important role in pain signal processing. However, the mechanisms by which the CSF-contacting nucleus intervenes in pain is unclear. The NRG1-ErbB4 signaling plays an important role in the nervous system and has been shown to be involved in the regulation of pain. ⋯ With immunofluorescence staining and Western blot, the NRG1-ErbB4 signaling in the CSF-contacting nucleus showed upregulated during the acute pain phase. And, activating NRG1-ErbB4 signaling in the CSF-contacting nucleus specifically by intracranial injection of drugs, the naïve mice displayed thermal hyperalgesia while inhibiting this signaling by intracranial injection could reverse the hyperalgesia caused by CSF-contacting nucleus activation, and execute an analgesic effect during the painful phase in mice. Our study suggested that the CSF-contacting nucleus plays a regulatory role in thermal pain in mice via NRG1-ErbB4 signaling.
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As the incidence and survival rates of patients with cancer continues to grow, an increasing number of people are living with comorbidities, which often manifests as cancer-induced bone pain (CIBP). The majority of patients with CIBP report poor pain control from currently available analgesics. A conotoxin, Contulakin-G (CGX), has been demonstrated to be an antinociceptive agent in postsurgical and neuropathic pain states via a neurotensin receptor 2 (NTSR2)-mediated pathway. ⋯ Moreover, at antinociceptive doses, CGX had no impact on motor behavior in rodents with CIBP. Finally, RNAScope and immunoblotting analysis revealed expression of NTSR2 in both dorsal and ventral horns, while Cav2.3 was minimally expressed in the ventral horn, possibly explaining the sensory selectivity of CGX. Together, these findings support advancing CGX as a potential therapeutic for cancer pain.
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Sensory profiling in neuropathic pain using quantitative sensory testing (QST) has not been extended to central neuropathic pain due to spinal cord injury (SCI). This study aims to fill this gap by evaluating sensory profiles in patients with neuropathic SCI pain. ⋯ The evaluation of sensory phenotypes by quantitative sensory testing in central neuropathic pain due to SCI adds a new perspective on sensory phenotypes in comparison to peripheral neuropathic pain. The described thermal and mechanical hyperalgesia combination might represent involvement of the spinothalamic tract. In addition, there was a trend towards older age and longer time since injury in patients with loss of function.