Articles: hyperalgesia.
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J. Pharmacol. Exp. Ther. · Sep 2007
Agmatine induces antihyperalgesic effects in diabetic rats and a superadditive interaction with R(-)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid, a N-methyl-D-aspartate-receptor antagonist.
Agmatine, an endogenous cationic amine resulting from the decarboxylation of L-arginine, produces antihyperalgesic and antiallodynic effects in animal models of chronic neuropathic and inflammatory pain. We examined the effect of agmatine on tactile and thermal allodynia and on mechanical hyperalgesia in streptozocin-induced diabetic rats. To determine its mechanism of action and the potential interest of some of its combinations, the antihyperalgesic effect of agmatine was challenged with alpha(2)-adrenergic imidazoline and opioid-receptor antagonists, and its interaction with the opioid-receptor agonist morphine, the competitive N-methyl-D-aspartate receptor antagonist D-CPP [R(-)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid], and the nitric-oxide synthase inhibitor L-NAME (L-N(G)-nitro-L-arginine methyl ester) were examined. ⋯ L-NAME or with i.t. morphine resulted in an additive antihyperalgesic effect, whereas the agmatine/D-CPP i.t. combination was superadditive. In summary, the present findings reveal that spinal agmatine produces antiallodynic and antihyperalgesic effects in diabetic neuropathic pain involving, at least for its antihyperalgesic effect, the imidazoline receptors. Moreover, agmatine combined with D-CPP produces an antinociceptive synergy in experimental neuropathy, opening opportunities in the development of new strategies for pain therapy.
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Journal of neurochemistry · Sep 2007
Activation of extracellular signal-regulated protein kinases 5 in primary afferent neurons contributes to heat and cold hyperalgesia after inflammation.
Heat and cold hyperalgesia is a common feature of inflammatory pain. To investigate whether activation of extracellular signal-regulated protein kinase 5 (ERK5), also known as big mitogen-activated protein kinase 1, in primary sensory neurons participates in inflammatory pain, we examined the phosphorylation of ERK5 in the dorsal root ganglion (DRG) after peripheral inflammation. Inflammation induced by complete Freund's adjuvant produced heat and cold hyperalgesia on the ipsilateral hind paw and induced an increase in the phosphorylation of ERK5, mainly in tyrosine kinase A-expressing small- and medium-size neurons. ⋯ Furthermore, the inhibition of ERK5 blocked the induction of transient receptor potential channel TRPV1 and TRPA1 expression in DRG neurons after peripheral inflammation. Our results show that ERK5 activated in DRG neurons contribute to the development of inflammatory pain. Thus, blocking ERK5 signaling in sensory neurons that has the potential for preventing pain after inflammation.
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Although electroacupuncture (EA) therapy is used to relieve various kinds of pain, the optimal frequency and duration of EA remain unclear. We investigated the effect of varying frequency and duration of EA during hyperalgesia elicited by carrageenan-induced inflammation. ⋯ These results show that EA produces electroacupuncture analgesia of carrageenan-induced hyperalgesia. These findings also suggest that, among the frequencies and durations tested, EA at 3Hz (60 minutes) is the most suitable frequency and duration for carrageenan-induced inflammation. It seems that EA has different analgesic effects and mechanisms according to the parameters of stimulation. For EA in the clinical induction of analgesia, it is especially important that an effective frequency and duration are selected.
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Aug 2007
Intracisternal administration of mitogen-activated protein kinase inhibitors reduced mechanical allodynia following chronic constriction injury of infraorbital nerve in rats.
The present study investigated the role of mitogen-activated protein kinase (MAPK) in orofacial neuropathic pain following chronic constriction injury of the infraorbital nerve (ION-CCI). Experiments were carried out on male Sprague-Dawley rats weighing between 200 and 230 g. The ION was separated from adhering tissue, and two ligatures (5-0 chromic gut) were tied loosely around it. ⋯ Intracisternal administration with PD98059 or SB203580, a MEK inhibitor or a p38 MAPK inhibitor, respectively, significantly inhibited ION-CCI-induced mechanical allodynia in the orofacial area. These results indicate that the ION-CCI produced behavioral alterations in the orofacial area and those central MAPKs pathways contribute to orofacial neuropathic pain. Our findings suggest that MAPKs inhibitors have a potential role in treatment for orofacial neuropathic pain.
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Based on the well established involvement of IL-1beta in inflammatory hyperalgesia, we have assessed the possible role played by IL-1beta in a murine model of bone cancer-induced pain. With this aim, we measured IL-1beta levels at the region of the tibia and the spinal cord in mice bearing a tibial osteosarcoma induced by the inoculation of NCTC 2472 cells, and we tested whether the IL-1 receptor antagonist, anakinra, inhibits some hypernociceptive reactions evoked by the neoplastic injury. Parallel experiments were performed in mice with a chronic inflammatory process (intraplantar injection of complete Freund's adjuvant, CFA). ⋯ Anakinra, intrathecally administered (1 and 10 microg) did not modify hyperalgesia of either origin. Besides, both tumoral and inflammatory mechanical allodynia remained unaltered after the administration of anakinra. In conclusion, some hyperalgesic symptoms observed in this model of bone cancer are mediated by the peripheral release of IL-1beta and may be inhibited by antagonists of type I IL-1 receptors with a similar or greater potency than symptoms produced by inflammation.