European journal of pharmacology
-
Type 2 diabetes is a risk factor for Alzheimer's disease. Insulin receptor desensitisation has been found in Alzheimer brains, which may be the underlying link. Glucose-dependent insulinotropic polypeptide (GIP), an incretin hormone, normalises insulin signalling in diabetes. ⋯ In LTP recording in area CA1, both (Pro3)GIP as well as D-Ala2GIP enhanced LTP formation. In addition, the proliferation of neuronal progenitor cells in the dentate gyrus was increased both by D-Ala2GIP and (Pro3)GIP. The results show that the antagonist (Pro3)GIP has agonistic effects in chronic use, and both (Pro3)GIP and the agonist D-Ala2GIP are safe to use in wt mice and induces no major behavioural side effects nor impairments in learning whilst enhancing LTP and neuronal progenitor cell proliferation, which may be useful in treating neurodegenerative diseases.
-
The present study examined effects of caffeine on antinociception by acetaminophen in the formalin test in mice. It demonstrates that caffeine 10mg/kg inhibits antinociception produced by acetaminophen 300 mg/kg i.p. against phase 2 flinches. Chronic administration of caffeine in the drinking water (0.1, 0.3g/l) for 8 days also inhibits the action of acetaminophen. ⋯ Caffeine reversal of acetaminophen results from actions in the spinal cord, as intrathecal DPCPX 10 nmol inhibited antinociception by systemic acetaminophen; this was also observed in +/+ but not in -/- adenosine A(1) receptor mice. We propose that spinal adenosine A(1) receptors contribute to the action of acetaminophen secondarily to involvement of descending serotonin pathways and release of adenosine within the spinal cord. Inhibition of acetaminophen antinociception by doses of caffeine relevant to dietary human intake levels suggests a more detailed consideration of acetaminophen-caffeine interactions in humans is warranted.
-
Postoperative pain and its control remain one of the most important issues in the field of surgery and health care systems. Morphine is a potent and effective analgesic, but substance abuse patients can manifest cross-tolerance to it, making it difficult to satisfy their analgesic/anesthetic requirements. As carbamazepine has shown antinociceptive properties in a variety of experimental and clinical settings, in the present study, we evaluated its potential antiallodynic effects on postoperative pain in naïve and morphine-dependent rats. ⋯ In contrast, 5mg/kg carbamazepine did not significantly alter PWT in naives but it was effective in dependent rats. 10 and 15 mg/kg carbamazepine attenuated allodynia following surgery in both groups. Co-administration of 5mg/kg carbamazepine with 3mg/kg morphine produced higher analgesia in morphine-dependent incised rats and prolonged antinociception as compared to morphine alone (P<0.05). Thus carbamazepine may potentiate the analgesic effect of chronically administered morphine on postoperative pain model in morphine-dependent rats.
-
Arthritic pain is a serious health problem that affects a large number of patients. Toll-like receptors (TLRs) activation within the joints has been implicated in pathophysiology of arthritis. However, their role in the genesis of arthritic pain needs to be demonstrated. ⋯ In last instance, their hypernociceptive effects were dependent on the production of hypernociceptive mediators, prostaglandins and sympathetic amines. These results indicate that in zymosan-induced experimental arthritis, TLR2/MyD88 is involved in the cascade of events of joint hypernociception through a mechanism dependent on cytokines and chemokines production. Thus, TLR2/MyD88 signaling might be a target for the development of novel drugs to control pain in arthritis.