Articles: hyperalgesia.
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The present study was carried out to examine global gene expression in the brainstem, in a mouse facial carrageenan injection model of orofacial pain. Mice that received facial carrageenan injection showed increased mechanical allodynia, demonstrated by increased responses to von Frey hair stimulation of the face. The brainstem was harvested at 3 days post-injection, corresponding to the time of peak responses, and analyzed by Affymetrix Mouse Genome 430 2.0 microarrays. ⋯ Intraperitoneal injection of the P-selectin inhibitor KF38789 significantly reduced mechanical allodynia in the facial carrageenan-injected mice. P-selectin mediates the capturing of leukocytes from the bloodstream and rolling of leukocytes along the endothelial surface. We hypothesize that increased nociceptive input to the brainstem could attract circulating macrophages into the brain, resulting in neuroinflammation and pain.
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Lysophosphatidic acid (LPA) signaling, through LPA(1) receptor and its downstream RhoA, has been reported to initiate nerve injury-induced neuropathic pain. In the present study, we performed gene expression profiling of the dorsal root ganglion (DRG) to identify genes induced by intrathecal injection of LPA in a botulinum toxin C3 (BoNT/C3)-reversible manner. We selected and functionally characterized ephrinB1 from 82 identified genes as a potential gene involved in pain transmission, since ephrinB1 is implicated to modulate N-methyl-d-aspartate (NMDA) receptor functions in spinal pain transmission. ⋯ In addition, intrathecal treatment with a soluble ligand, ephrinB1-Fc, caused similar neuropathic pain-like behaviors in a manner that was reversible by the NMDA receptor antagonist MK-801. These results suggest that ephrinB1 plays a crucial role in LPA-induced neuropathic pain. In addition, the present study may provide a new strategy to identify unique neuropathic pain-related genes.
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Hydrogen sulfide (H2S), a gasotransmitter, facilitates membrane currents through T-type Ca2+ channels, and intraplantar (i.pl.) administration of NaHS, a donor of H2S, causes prompt hyperalgesia in rats. In this context, we asked whether intrathecal (i.t.) administration of NaHS could mimic the hyperalgesic effect of i.pl. NaHS in rats, and then examined if Cav3.2 isoform of T-type Ca2+ channels contributed to the pro-nociceptive effects of i.t. and i.pl. ⋯ Repeated i.t. administration of antisense oligodeoxynucleotides (ODNs) targeting rat Cav3.2, but not mismatch ODNs, caused silencing of Cav3.2 protein in the dorsal root ganglia and spinal cord, and then attenuated the hyperalgesia induced by either i.t. or i.pl. NaHS. Our findings thus establish that spinal and peripheral NaHS/H2S activates or sensitizes Cav3.2 T-type Ca2+ channels expressed in the primary afferents and/or spinal nociceptive neurons, leading to sensitization of nociceptive processing and hyperalgesia.
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The behavioural noxious heat threshold i.e. the lowest temperature evoking nocifensive behaviour was previously shown to decrease in short-lasting, but not in sustained, inflammatory thermal hyperalgesias. The aim of this study was to examine whether the surgical incision-induced lasting heat hyperalgesia involves a drop of the heat threshold and to assess the effects of conventional opioid and non-opioid analgesics in this model. One of the hind paws of rats was immersed into a water bath whose temperature was near-linearly increased from 30 degrees C until the animal withdrew its paw from the water. ⋯ Thermal hyperalgesia was also decreased by intraplantar treatment with morphine (10 microg) or diclofenac (100 microg). In conclusion, the incision-induced sustained thermal hyperalgesia in rats involves a drop of the heat threshold suggesting that mechanisms of postsurgical pain are distinct from those of pure inflammatory pain. The thermal antihyperalgesic actions of systemically and/or locally applied morphine, diclofenac and paracetamol could be detected with high temporal resolution and sensitivity in this model.
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Indian J. Exp. Biol. · Mar 2009
Anti-nociceptive effect of duloxetine in mouse model of diabetic neuropathic pain.
The involvement of adenosinergic pathway in the anti-nociceptive effect of duloxetine, a balanced 5-HT/NE reuptake inhibitor, was evaluated in streptozotocin induced diabetic male albino mice of Laca strain. After four weeks of single injection of streptozotocin (200 mg/kg, ip), mice were tested in the tail immersion and hot-plate assays. Cerebral adenosine levels were measured by high-performance liquid chromatography (HPLC/PDA detector). ⋯ Administration of duloxetine (5, 10 and 20 mg/kg, ip) to diabetic mice produced dose-dependent anti-nociceptive effect in both tail-immersion and hot-plate assays. Adenosine levels were also significantly and dose-dependently increased by different doses of duloxetine. The results demonstrated the involvement of adenosinergic pathway in duloxetine mediated anti-hyperalgesia in diabetic neuropathic pain.