European journal of pharmacology
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Comparative Study
Comparative efficacy of 3 soluble epoxide hydrolase inhibitors in rat neuropathic and inflammatory pain models.
Epoxy-fatty acids have been recognized as important cell signaling molecules with multiple biological effects including anti-nociception. The main degradation pathway of these signaling molecules is via the soluble epoxide hydrolase (sEH) enzyme. Inhibitors of sEH extend the anti-nociceptive effects of fatty acid epoxides. ⋯ Inhibiting the sEH enzyme in these models successfully blocked pain related behavior in both models. The sEH inhibitors were more potent and more efficacious than celecoxib in reducing both diabetic neuropathic pain and lipopolysaccharide induced inflammatory pain. Because of their ability to block diabetic neuropathic pain sEH inhibition is a promising new approach to treat chronic pain conditions.
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Comparative Study
Analgesic effects of the non-nitrogen-containing bisphosphonates etidronate and clodronate, independent of anti-resorptive effects on bone.
Nitrogen-containing bisphosphonates (NBPs) have greater anti-bone-resorptive effects than non-nitrogen-containing bisphosphonates (non-NBPs). Hence, NBPs are the current first-choice drug for osteoporosis. However, NBPs carry a risk of osteonecrosis of jaws. ⋯ Etidronate and clodronate each displayed an analgesic effect in the capsaicin test. Etidronate and clodronate displayed their analgesic effects at doses lower than those inducing anti-bone-resorptive effects. These results suggest that etidronate and clodronate exert potent, anti-bone-resorptive effect-independent analgesic effects, possibly via an interaction with neurons, and that they warrant reappraisal as safe drugs for osteoporosis.
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Heat stroke is a life-threatening illness characterized by an elevated core body temperature. Despite adequate lowering of the body temperature and support treatment of multiple organ-system function, heat stroke is often fatal. 3-(5'-Hydoxymethyl-2'-furyl)-1-benzyl-indazol (YC-1) been identified as an activator of soluble guanylate cyclase. To evaluate whether YC-1 protects multiple organ dysfunctions and improves survival during heat stroke and its mechanism. ⋯ The expression of Hsp70 and HSF-1 in liver and renal of YC-1+HS group was significantly higher than that of HS group. All of the protective effects of YC-1 were all significantly suppressed when pretreated with quercetin (400mg/kg). Results indicate that YC-1 may improve survival due to induce Hsp70 overexpression.
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Neuropathic pain results from lesions or diseases affecting the somatosensory system. The management of patients with chronic neuropathic pain remains a challenge. Several studies support the crucial role of neuroactive steroids in the modulation of pain. ⋯ The chronic administration of progesterone significantly reduced the behavioral scores of cold- and mechano-allodynia and heat hyperalgesia but single dose of progesterone did not have any effect on behavioral scores of neuropathic pain. Our data indicate that the early chronic administration of progesterone prevents the development of neuropathic pain but its acute injection does not change the expression of neuropathic pain. These results suggest that progesterone could be considered as a new approach for management of neuropathic pain.
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The effect of the (R,S)-ketamine metabolites (R,S)-norketamine, (R,S)-dehydronorketamine, (2S,6S)-hydroxynorketamine and (2R,6R)-hydroxynorketamine on the activity of α7 and α3β4 neuronal nicotinic acetylcholine receptors was investigated using patch-clamp techniques. The data indicated that (R,S)-dehydronorketamine inhibited acetylcholine-evoked currents in α7-nicotinic acetylcholine receptor, IC(50) = 55 ± 6 nM, and that (2S,6S)-hydroxynorketamine, (2R,6R)-hydroxynorketamine and (R,S)-norketamine also inhibited α7-nicotinic acetylcholine receptor function at concentrations ≤ 1 μM, while (R,S)-ketamine was inactive at these concentrations. ⋯ The calculated K(i) values were 38.95 μM for (S)-dehydronorketamine, 21.19 μM for (2S,6S)-hydroxynorketamine and>100 μM for (2R,6R)-hydroxynorketamine. The results suggest that the inhibitory activity of ketamine metabolites at the α7-nicotinic acetylcholine receptor may contribute to the clinical effect of the drug.