Articles: hyperalgesia.
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Comparative Study Observational Study
Incidence of persistent postoperative pain after hepatectomies with 2 regimes of perioperative analgesia containing ketamine.
Studies designed to assess persistent postoperative pain (PPP) incidence after hepatectomies are lacking. Our aim was to assess PPP incidence 6 months after hepatectomies with intravenous (IV) or epidural (EPI) analgesia containing ketamine. Prospective observational comparative study between 2 cohorts of patients submitted to hepatectomy. ⋯ IV group showed more cognitive side effects. Incidence of PPP at 6 months after open hepatectomies with EPI or IV analgesia containing ketamine was lower than previously reported for other abdominal surgeries. Ketamine influence on low PPP incidence and hyperalgesia cannot be discarded.
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Objective A prospective clinical imaging study has been conducted to investigate pain processing functional pathways during trigeminal heat stimulation (THS) in patients with migraine without aura experiencing ictal cutaneous allodynia (CA) (MwoA CA+). Methods Using whole-brain BOLD-fMRI, functional response to THS at three different intensities (41°, 51° and 53℃) was investigated interictally in 20 adult MwoA CA+ patients compared with 20 MwoA patients without ictal CA (MwoA CA-) and 20 healthy controls (HCs). Secondary analyses evaluated associations between BOLD signal change and clinical features of migraine. ⋯ Furthermore, during high-noxious THS (53℃) a significantly decreased activation in the secondary somatosensory cortices was observed in (a) MwoA CA- patients compared to both MwoA CA+ patients and HCs and (b) MwoA CA+ patients compared to HCs. CA severity was positively correlated with the secondary somatosensory cortices activation. Conclusions Our findings suggest that CA may be subtended by both a dysfunctional analgesic compensatory mechanism and an abnormal internal representation of pain in migraine patients.
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We have recently shown that spinal sigma-1 receptor (Sig-1R) activation facilitates nociception via an increase in phosphorylation of the N-methyl-D-aspartate (NMDA) receptor GluN1 subunit (pGluN1). The present study was designed to examine whether the Sig-1R-induced facilitative effect on NMDA-induced nociception is mediated by D-serine, and whether D-serine modulates spinal pGluN1 expression and the development of neuropathic pain after chronic constriction injury (CCI) of the sciatic nerve. Intrathecal administration of the D-serine degrading enzyme, D-amino acid oxidase attenuated the facilitation of NMDA-induced nociception induced by the Sig-1R agonist, 2-(4-morpholinethyl)1-phenylcyclohexane carboxylate. Exogenous D-serine increased protein kinase C (PKC)-dependent (Ser896) pGluN1 expression and facilitated NMDA-induced nociception, which was attenuated by preteatment with the PKC inhibitor, chelerythrine. In CCI mice, administration of the serine racemase inhibitor, L-serine O-sulfate potassium salt or D-amino acid oxidase on postoperative days 0 to 3 suppressed CCI-induced mechanical allodynia (MA) and pGluN1 expression on day 3 after CCI surgery. Intrathecal administration of D-serine restored MA as well as the GluN1 phosphorylation on day 3 after surgery that was suppressed by the Sig-1R antagonist, N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine dihydrobromide or the astrocyte inhibitor, fluorocitrate. In contrast, D-serine had no effect on CCI-induced thermal hyperalgesia or GluN1 expression. These results indicate that spinal D-serine: 1) mediates the facilitative effect of Sig-1R on NMDA-induced nociception, 2) modulates PKC-dependent pGluN1 expression, and 3) ultimately contributes to the induction of MA after peripheral nerve injury. ⋯ This report shows that reducing D-serine suppresses central sensitization and significantly alleviates peripheral nerve injury-induced chronic neuropathic pain and that this process is modulated by spinal Sig-1Rs. This preclinical evidence provides a strong rationale for using D-serine antagonists to treat peripheral nerve injury-induced neuropathy.
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Endometriosis is an incurable gynecological disorder characterized by debilitating pain and the establishment of innervated endometriosis lesions outside the uterus. In a preclinical mouse model of endometriosis we demonstrated overexpression of the PGE2-signaling pathway (including COX-2, EP2, EP4) in endometriosis lesions, dorsal root ganglia (DRG), spinal cord, thalamus and forebrain. ⋯ We then tested TRPV1, EP2, and EP4 receptor antagonists: The EP2 antagonist was the most efficient analgesic, reducing primary hyperalgesia by 80% and secondary hyperalgesia by 40%. In this study we demonstrate reversible peripheral and central hyperalgesia in mice with induced endometriosis.
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Treatment of remifentanil-induced postoperative hyperalgesia (RIH) remains a clinical challenge because the mechanisms are not fully understood. Matrix metalloproteinase-9 (MMP-9) is a key component in neuroinflammation because of its facilitation of pro-inflammatory cytokine maturation. Therefore, inhibition of MMP-9 may represent a novel therapeutic approach to the treatment of RIH. ⋯ Intraperitoneal injection of N-acetyl-cysteine (NAC), a broadly used safe drug, significantly attenuated RIH via suppressing the activation of MMP-9 in DRGs. NAC inhibited the cleavage of IL-1β in DRGs, which is a critical substrate of MMP-9, and markedly suppressed glial activation and neuron excitability in spinal dorsal horn induced by remifentanil. These results demonstrated that NAC can effectively alleviate RIH via powerfully inhibiting MMP-9 activation in DRGs.