Brain research
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Primary afferent neurons in mammalian dorsal root ganglia (DRGs) normally function as independent sensory communication elements. However, it has recently been shown that most DRG neurons are transiently activated when axons of neighboring neurons of the same ganglion are stimulated repetitively and the cross-depolarization contributes to this mutual cross-excitation. Here, we reported the cross-inhibition of mechanoreceptive information in DRG under peripheral inflammatory condition. ⋯ This interaction was not affected by cutting the dorsal roots at the place close to the recorded DRG. Preapplication of naloxone and yohimbine did not block the interaction. Taken together with previous reports, this intraganglionic cross-talking appears to be mediated by collision of retrograde spread of action potentials, or/and at least in part, by an activity-dependent diffusible excitatory substance released from neuronal somata and/or adjacent axons, and detected by neighboring cell somata.
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Peripheral nerve injury in rodents results in hypersensitivity to mechanical and thermal stimuli accompanied by reduced antinociceptive efficacy of opioids and, in some models, sensitivity to sympathetic blockade. alpha2-Adrenergic receptor agonists increase in potency and efficacy after nerve injury in rodents and effectively relieve neuropathic pain in humans who do not get pain relief from opioids. However, the underlying mechanisms are unclear. It has been well known that the major noradrenergic innervation of the spinal dorsal horn originates from the locus coeruleus nucleus (LC) in the brainstem. ⋯ Interestingly, in the lower lumbar and upper sacral spinal dorsal horn, numerous TH-IR neurons were observed in the superficial dorsal horn (primarily lamina I). CCI of the sciatic nerve did not change the number of these TH-IR cells. These findings suggest that augmented descending inhibitory noradrenergic innervation to the dorsal horn could be one of the mechanisms underlying the increased effectiveness in the anti-allodynic effect elicited by alpha2-adrenergic receptor agonists.
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The recent development of rodent models of bone cancer pain has started to provide the basis for demonstrating the particular neurochemical and behavioral entity of cancer pain. Behaviourally, both spontaneous pain and hyperalgesia related to mechanical, but not thermal, noxious stimuli have been described in cancer-bearing animals. We have carried out a histological and behavioural study focused on the reactivity to noxious heat in C3H/HeJ mice receiving an intratibial injection of 10(5) NCTC 2472 cells. ⋯ This thermal hyperalgesia was prevented by the systemic administration of morphine (15 mg/kg). Throughout the whole period studied, mice showed signs of spontaneous pain behaviour that reached its maximum 3 weeks after inoculation. In conclusion, we show that the presence of thermal heat hyperalgesia is preceded by an initial opioid-mediated hypoalgesic state, in this murine model of bone cancer pain.
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It has been reported that cerebral ischemia induces Thr286 autophosphorylation and translocation of CaMKIIalpha which targets to and phosphorylates NR2B in hippocampus of rats [Neuroscience 96 (2000) 665; J. Biol. Chem. 275 (2000) 23798]. ⋯ Thirdly, our results indicated the concomitant phosphorylation and dephosphorylation of CaMKII and NR2B following ischemia or longer reperfusion. Moreover, the dissociation of CaMKII from NR2B had the same trend as that of the return of CaMKII to cytosol. All these data imply the close relationships between CaMKII and NR2B during ischemia and reperfusion, namely, CaMKII might act as an amplifier of detrimental cellular calcium signal regulated by NMDA receptors when becoming autophosphorylated and targeting to NR2B; conversely, autophosphorylated CaMKII could modulate NMDA receptor channel properties by phosphorylating NR2B.
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We have previously shown that RB101, a dual inhibitor of enkephalin-degrading enzymes, decreased carrageenin-evoked c-Fos protein expression at the spinal cord level in awake rats. Moreover, we have also shown that c-Fos expression is a useful marker of the possible direct or indirect interactions between neural pathways, such as opioid and cholecystokinin systems. We now investigated the respective roles of the three main types of opioid receptors (mu, delta, or kappa) and their possible interactions, in the depressive effects of RB101 in inflammatory nociceptive conditions induced by intraplantar carrageenin (6 mg/150 microl of saline). ⋯ This effect was completely blocked by beta-FNA (10 mg/kg, i.v.), or NTI (1 mg/kg, i.v.). In contrast, BNI (2.5 mg/kg, i.v.) did not reverse the reducing effects of RB101(S) on carrageenin-evoked c-Fos protein expression. These results suggest that functional interactions occur between mu- and delta-opioid receptors in enkephalin-induced antinociceptive effects.