Articles: hyperalgesia.
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Accidental mandibular nerve injury may occur during tooth extraction or implant procedures, causing ectopic orofacial pain. The exact mechanisms underlying ectopic orofacial pain following mandibular nerve injury is still unknown. Here, we investigated the role of macrophages and tumor necrosis factor alpha (TNFα) in the trigeminal ganglion (TG) in ectopic orofacial pain following inferior alveolar nerve transection (IANX). ⋯ These findings suggest that signaling cascades resulting from the production of TNFα by infiltrated macrophages in the TG contributes to the development of ectopic mechanical allodynia in whisker pad skin following IANX.
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Comparative Study
Novel Endomorphin Analogs are More Potent and Longer Lasting Analgesics in Neuropathic, Postoperative, Inflammatory, and Visceral Pain Relative to Morphine.
Activation of the mu-opioid receptor provides the gold standard for pain relief, but most opioids used clinically have adverse effects that have contributed to an epidemic of overdose deaths. We recently characterized mu-opioid receptor selective endomorphin (EM) analogs that provide potent antinociception with reduction or absence of a number of side effects of traditionally prescribed opioids including abuse liability, respiratory depression, motor impairment, tolerance, and inflammation. The current study explores the effectiveness of these EM analogs relative to morphine in four major pain models by intrathecal as well as intravenous administration in male Sprague Dawley rats and subcutaneous administration in male CD-1 mice. In the spared nerve injury model of neuropathic pain, mechanical allodynia and mechanical hyperalgesia were assessed with von Frey and Randall-Selitto tests, respectively. In the paw incision model of postoperative pain, von Frey testing was used to assess mechanical allodynia and thermal hyperalgesia was evaluated with Hargreaves testing. In the Complete Freund's Adjuvant model of inflammatory pain, thermal hyperalgesia was assessed using Hargreaves testing. In CD-1 mice, visceral pain was assessed with the acetic acid writhing test. In all cases, EM analogs had equal or greater potency and longer duration of action relative to morphine. The data suggest that EM analogs, particularly analog 4 (ZH853), could provide effective therapy for a diverse spectrum of pain conditions with low risk of adverse side effects compared with currently used opioids such as morphine. ⋯ Novel EM analogs show equal or greater potency and effectiveness relative to morphine in multiple pain models. Together with substantially reduced side effects, including abuse liability, the compounds show promise for addressing the critical need for effective pain relief as well as reducing the opioid overdose epidemic.
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Best Pract Res Clin Anaesthesiol · Dec 2017
ReviewDo we feel pain during anesthesia? A critical review on surgery-evoked circulatory changes and pain perception.
The difficulty of defining the three so-called components of « an-esthesia » is emphasized: hypnosis, absence of movement, and adequacy of anti-nociception (intraoperative « analgesia »). Data obtained from anesthetized animals or humans delineate the activation of cardiac and vasomotor sympathetic reflex (somato-sympathetic reflex) and the cardiac parasympathetic deactivation observed following somatic stimuli. Sympathetic activation and parasympathetic deactivation are used as monitors to address the adequacy of intraoperative anti-nociception. Finally, intraoperative nociception through the administration of nonopioid analgesics vs. opioid analgesics is considered to achieve minimal postoperative side effects.
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Randomized Controlled Trial
Intraoperative naloxone reduces remifentanil-induced postoperative hyperalgesia but not pain: a randomized controlled trial.
Intraoperative use of a high-dose remifentanil may induce postoperative hyperalgesia. Low-dose naloxone can selectively reverse some adverse effects of opioids without compromising analgesia. We thus hypothesized that the intraoperative use of a high-dose remifentanil combined with a low-dose naloxone infusion reduces postoperative hyperalgesia compared with the use of remifentanil alone. ⋯ NCT02856087.
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Best Pract Res Clin Anaesthesiol · Dec 2017
ReviewOpioid-free anesthesia opioid side effects: Tolerance and hyperalgesia.
Opioids are the most potent drugs used to control severe pain. However, neuroadaptation prevents opioids' ability to provide long-term analgesia and produces opposite effects, i.e., enhancement of existent pain and facilitation of chronic pain development. Neuroadaptation to opioids use results in the development of two interrelated phenomena: tolerance and "opioid-induced hyperalgesia" (OIH). ⋯ Conversely, observations of improved patient's recovery after opioid-sparing anesthesia techniques stand as an indirect evidence that perioperative opioid administration deserves caution. To date, perioperative OIH has rarely been objectively assessed by psychophysics tests in patients. A direct relationship between the presence of perioperative OIH and patient outcome is missing and certainly deserves further studies.