Thermal hyperalgesia in association with the development of morphine tolerance in rats: roles of excitatory amino acid receptors and protein kinase C. Loss of μ opioid receptor signaling in nociceptors, but not microglia, abrogates morphine tolerance without disrupting analgesia.
2008 10:537–51.Ĭorder G, Tawfik VL, Wang D, Sypek EI, Low SA, Dickinson JR, et al. Opioid tolerance development: a pharmacokinetic/pharmacodynamic perspective. Mechanisms of hyperalgesia and morphine tolerance: a current view of their possible interactions. Perioperative opioid analgesia-when is enough too much? A review of opioid-induced tolerance and hyperalgesia. Our results reveal an important role of morphine-induced astrogliosis in OIH pathogenesis and elucidate a neuron-to-astrocyte intercellular Wnt signaling pathway that controls the astrogliosis.Ĭolvin LA, Bull F, Hales TG. Furthermore, we showed that the Wnt5a-ROR2 signaling-dependent astrogliosis contributes to OIH via inflammasome-regulated IL-1β. Conditional knock-out of Wnt5a in neurons or its co-receptor ROR2 in astrocytes blocked not only morphine-induced astrogliosis but also OIH and NCP. We found that Wnt5a is a neuron-to-astrocyte signal that is required for morphine-induced astrogliosis. Genetic reduction of astrogliosis inhibited the expression of OIH and morphine-induced neural circuit polarization (NCP) in the spinal dorsal horn (SDH). astrogliosis) are critical for OIH development in both male and female mice. Here, we show that reactive astrocytes (a.k.a. Although glial cells are known to become reactive in OIH animal models, their biological contribution to OIH remains to be defined and their activation mechanism remains to be elucidated. Neuronal malplasticity in pain circuits has been the predominant proposed mechanism of OIH expression. Paradoxically, repeated use of opioid analgesics may cause an exacerbated pain state known as opioid-induced hyperalgesia (OIH), which significantly contributes to dose escalation and consequently opioid overdose. Opioids are the frontline analgesics for managing various types of pain.
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