Life sciences
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Comparative Study
The benzomorphan-based LP1 ligand is a suitable MOR/DOR agonist for chronic pain treatment.
Powerful analgesics relieve pain primarily through activating mu opioid receptor (MOR), but the long-term use of MOR agonists, such as morphine, is limited by the rapid development of tolerance. Recently, it has been observed that simultaneous stimulation of the delta opioid receptor (DOR) and MOR limits the incidence of tolerance induced by MOR agonists. 3-[(2R,6R,11R)-8-hydroxy-6,11-dimethyl-1,4,5,6-tetrahydro-2,6-methano-3-benzazocin-3(2H)-yl]-N-phenylpropanamide (LP1) is a centrally acting agent with antinociceptive activity comparable to morphine and is able to bind and activate MOR and DOR. The aim of this work was to evaluate and compare the induction of tolerance to antinociceptive effects from treatment with LP1 and morphine. ⋯ LP1 is a novel analgesic agent for chronic pain treatment, and its low tolerance-inducing capability may be correlated with its ability to bind both the MOR and DOR.
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Although anisodamine, a muscarinic acetylcholine receptor antagonist, has been used in China for treating various shocks for many years, the mechanisms are not well understood. Our previous studies have demonstrated anisodamine exerts its cholinergic anti-inflammatory action through indirectly activating α7 nicotinic acetylcholine receptors (α7 nAChR). Because IL-10 is a critical anti-inflammatory factor, we investigated its potential role in the antishock action of anisodamine. ⋯ These findings demonstrate that IL-10 plays an important role in the antishock action of anisodamine. It acts through upregulating α7 nAChR synergistically with anisodamine.
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Chronic stress-related conditions are often associated with stress-induced hyperalgesia. However, the neural circuitry responsible for producing stress-induced hyperalgesia is not well characterized. The aim of this study was to determine the contribution of mu-opioid expressing brainstem neurons to the expression of stress-induced hyperalgesia. ⋯ The finding that chronic stress produces mechanical hypersensitivity through circuitry that involves the RVM provides a potential neurobiological basis for the complex interaction between chronic stress and pain.
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We investigated the effects of in vivo intrastriatal administration of glycine (Gly), which is found at high concentrations in the brain of patients affected by nonketotic hyperglycinemia (NKH), on important parameters of oxidative stress. ⋯ The data shows that Gly in vivo administration causes lipid peroxidation, probably secondary to NMDA stimulation, induces protein oxidation and modulates the activities of important antioxidant enzymes in the striatum. In case these findings can be extrapolated to the human NKH, it is feasible that oxidative stress may be involved in the pathophysiology of the brain injury observed in patients with this neurometabolic disease.