Brain research
-
Comparative Study
Intrathecal interleukin-1beta administration induces thermal hyperalgesia by activating inducible nitric oxide synthase expression in the rat spinal cord.
The effect of the pro-inflammatory cytokine interleukin-1beta (IL-1beta) on the inducible nitric oxide synthase-nitric oxide (iNOS-NO) cascade in nociceptive signal transduction was examined in the intact rat spinal cord. All rats were implanted with an intrathecal (i.t.) catheter; some were also implanted with an i.t. microdialysis probe. The paw withdrawal latency to radiant heat was used to assess thermal hyperalgesia. ⋯ Neither 1400W nor artificial CSF (aCSF) affected the thermal nociceptive threshold and NO production. These results demonstrate that i.t. administration of IL-1beta induced thermal hyperalgesia by activating the iNOS-NO cascade in the rat spinal cord. On the basis of the present findings, we suggest that i.t. administration of iNOS inhibitors may have potential in the treatment of inflammatory and neuropathic pain syndromes.
-
Comparative Study
Effects of mitochondrial dysfunction on glutamate receptor-mediated neurotoxicity in cultured rat spinal motor neurons.
Glutamate-induced excitotoxicity is implicated as playing a key role in the pathogenesis of amyotrophic lateral sclerosis (ALS), and mitochondrial dysfunction is also found in ALS patients. We investigated the relationship between glutamate excitotoxicity and mitochondrial dysfunction elicited by rotenone (a complex I inhibitor), malonate (a complex II inhibitor), or antimycin (a complex III inhibitor), in primary cultures of the embryonic rat spinal cord. Rotenone and malonate induced relatively selective toxicity against motor neurons as compared to non-motor neurons, whereas antimycin caused non-selective toxicity. ⋯ When mitochondrial complex I was mildly inhibited by a sub-lethal concentration of rotenone, AMPA-induced motor neuron death was significantly exacerbated. A sub-lethal concentration of malonate exacerbated both NMDA- and AMPA-induced motor neuron death. These data suggest that mitochondrial dysfunction predisposes motor neurons to ionotropic glutamate receptor-mediated excitotoxicity.
-
In the view of importance of intergeniculate leaflet in circadian rhythms processes and lack of information about electrophysiological properties of isolated intergeniculate leaflet (IGL) neurons, we carried out extracellular recordings of the spontaneous activity of rat IGL cells in vitro. Unlike other structures of visual thalamus, IGL neurons have the ability to generate a robust spontaneous neuronal activity when maintained in vitro. We have observed that in a standard incubation fluid IGL neurons display at least three distinct firing patterns: continuously irregular-with a wide variety of firing rates, tonic-with a very stable level of activity, and phasic (slow bursts)-with intermittent silent periods. Our study is the first electrophysiological demonstration of IGL neuronal activity in vitro.
-
Morphine analgesic potency following systemic administration was assessed in male and female mice undergoing prior and repeated intrathecal morphine injections. Although morphine ED50 values were significantly increased in both sexes relative to their respective saline-injected controls, the magnitude of tolerance was greater in females. Intrathecal injection alone had no effect on morphine analgesia. The data suggest that spinal mechanisms contribute to sex differences in analgesic tolerance following systemic morphine administration.