Articles: hyperalgesia.
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High molecular weight hyaluronan (HMWH), a prominent component of the extracellular matrix binds to and signals via multiple receptors, including cluster of differentiation 44 (CD44) and toll-like receptor 4 (TLR4). We tested the hypothesis that, in the setting of inflammation, HMWH acts at TLR4 to attenuate hyperalgesia. We found that the attenuation of prostaglandin E2 (PGE2)-induced hyperalgesia by HMWH was attenuated by a TLR4 antagonist (NBP2-26245), but only in male and ovariectomized female rats. ⋯ This treatment completely reversed HMWH-induced anti-hyperalgesia in male rats. Our results demonstrate a sex hormone-dependent, sexually dimorphic involvement of TLR4 in HMWH-induced anti-hyperalgesia, that is MyD88 dependent. PERSPECTIVE: The role of TLR4 in anti-hyperalgesia induced by HMWH is a sexually dimorphic, TLR4 dependent inhibition of inflammatory hyperalgesia that provides a novel molecular target for the treatment of inflammatory pain.
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Anesthesia and analgesia · Sep 2021
P2Y1 Purinergic Receptor Contributes to Remifentanil-Induced Cold Hyperalgesia via Transient Receptor Potential Melastatin 8-Dependent Regulation of N-methyl-d-aspartate Receptor Phosphorylation in Dorsal Root Ganglion.
Remifentanil can induce postinfusion cold hyperalgesia. N-methyl-d-aspartate receptor (NMDAR) activation and upregulation of transient receptor potential melastatin 8 (TRPM8) membrane trafficking in dorsal root ganglion (DRG) are critical to cold hyperalgesia derived from neuropathic pain, and TRPM8 activation causes NMDAR-dependent cold response. Contribution of P2Y1 purinergic receptor (P2Y1R) activation in DRG to cold pain hypersensitivity and NMDAR activation induced by P2Y1R upregulation in neurons are also unraveled. This study explores whether P2Y1R contributes to remifentanil-induced cold hyperalgesia via TRPM8-dependent regulation of NMDAR phosphorylation in DRG. ⋯ Attenuation of remifentanil-induced cold hyperalgesia by P2Y1R inhibition is attributed to downregulations in NMDAR expression and phosphorylation via diminishing TRPM8 expression and membrane trafficking in DRG.
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Glycinergic neurons and glycine receptors (GlyRs) exert a critical control over spinal nociception. Prostaglandin E2 (PGE2), a key inflammatory mediator produced in the spinal cord in response to peripheral inflammation, inhibits a certain subtype of GlyRs (α3GlyR) that is defined by the inclusion of α3 subunits and distinctly expressed in the lamina II of the spinal dorsal horn, ie, at the site where most nociceptive nerve fibers terminate. Previous work has shown that the hyperalgesic effect of spinal PGE2 is lost in mice lacking α3GlyRs and suggested that this phenotype results from the prevention of PGE2-evoked protein kinase A (PKA)-dependent phosphorylation and inhibition of α3GlyRs. ⋯ In behavioral experiments, they showed no alterations in baseline nociception, but were protected from the hyperalgesic effects of intrathecally injected PGE2 and exhibited markedly reduced inflammatory hyperalgesia. These behavioral phenotypes closely recapitulate those found previously in GlyR α3-deficient mice. Our results thus firmly establish the crucial role of PKA-dependent phosphorylation of α3GlyRs in inflammatory hyperalgesia.
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Meta Analysis
Exploring the pain in patellofemoral pain: A systematic review and meta-analysis examining signs of central sensitization.
Patellofemoral pain (PFP) has high recurrence rates and minimal long-term treatment success. Central sensitization refers to dysfunctional pain modulation that occurs when nociceptive neurons become hyperresponsive. Researchers in this area of PFP have been increasingly productive in the past decade. ⋯ Signs of central sensitization were present in individuals with PFP, indicating altered pain modulation. The etiologic and treatment models of PFP should reflect the current body of evidence regarding central sensitization. Signs of central sensitization should be monitored clinically, and treatments with central effects should be considered as part of a multimodal plan of care.
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Meta Analysis Comparative Study
Evidence of Bilateral Localized, but Not Widespread, Pressure Pain Hypersensitivity in Patients With Upper Extremity Tendinopathy/Overuse Injury: A Systematic Review and Meta-Analysis.
The presence of altered nociceptive pain processing in patients with upper extremity tendinopathy/overuse injury is conflicting. Our aim was to compare pressure pain thresholds (PPTs) in symptomatic and distant pain-free areas between patients with upper extremity tendinopathy/overuse injury and controls. ⋯ Early identification of people with altered pain modulation could guide clinicians in treatment strategies. This review shows that there is a complex interplay between peripheral and central pain mechanisms in upper extremity tendinopathies/overuse injuries and that there likely are different subgroups of patients with upper extremity conditions.