Experimental neurology
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Experimental neurology · Feb 2001
Effect of peripheral nerve lesion and lumbar sympathectomy on peptide regulation in dorsal root ganglia in the NGF-overexpressing mouse.
Galanin is a peptide normally expressed at low levels both in sensory and in sympathetic neurons. It is strongly upregulated after peripheral nerve lesions, and it has been proposed that nerve growth factor (NGF) plays a role in this regulation. In the present study the effect of both sciatic nerve transection and lumbar sympathectomy on galanin in lumbar dorsal root ganglia (DRGs) was examined in mice overexpressing NGF (NGFOE) in the skin under the keratin promoter. ⋯ Our results show that high NGF levels in skin induce formation of pericellular baskets in DRGs expressing galanin- and TH-LI and that galanin in these baskets is strongly influenced by peripheral axotomy. However, overexpression of NGF did not markedly influence galanin expression in DRG neurons, neither normally nor after nerve lesions. Finally, expression of NPY in sympathetic ganglia is differently regulated in NGFOE compared to wild-type mice.
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Experimental neurology · Feb 2001
Pain behavior and response properties of spinal dorsal horn neurons following experimental diabetic neuropathy in the rat: modulation by nitecapone, a COMT inhibitor with antioxidant properties.
We attempted to characterize a spinal neuronal correlate of painful neuropathy induced by diabetes mellitus (DM). Pain behavior and response properties of spinal dorsal horn neurons were determined in rats with a streptozocin-induced DM. A catechol-O-methyltransferase inhibitor with potent antioxidant properties, nitecapone, was used in an attempt to attenuate neuropathic symptoms. ⋯ The results indicate that increased spontaneous activity in spinal dorsal horn WDR neurons may be causally related to behaviorally observed mechanical hypersensitivity in DM. Attenuation of the increased spontaneous activity in WDR neurons may explain the antihyperalgesic effect by nitecapone, due to naloxone- and alpha-2-adrenoceptor-insensitive mechanisms. DM or nitecapone treatment did not produce significant changes in phasic or tonic descending pain regulation originating in the RVM.
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Experimental neurology · Feb 2001
Retinal ganglion cell and nonneuronal cell responses to a microcrush lesion of adult rat optic nerve.
Injury of the optic nerve has served as an important model for the study of cell death and axon regeneration in the CNS. Analysis of axon sprouting and regeneration after injury by anatomical tracing are aided by lesion models that produce a well-defined injury site. We report here the characterization of a microcrush lesion of the optic nerve made with 10-0 sutures to completely transect RGC axons. ⋯ By 1 week after injury, axons regrew toward the lesion, but most stopped abruptly at the injury scar. The few axons that were able to cross the injury site did not extend further in the optic nerve white matter by 8 weeks postlesion. Our observations suggest that both the CSPG-positive scar and the myelin-derived growth inhibitory proteins contribute to the failure of RGC regeneration after injury.
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Experimental neurology · Jan 2001
Inhibition of inflammation-induced thermal hypersensitivity by sumatriptan through activation of 5-HT(1B/1D) receptors.
Migraine is effectively treated by drugs acting via 5-HT(1B/1D) receptors; however, the antinociceptive effects of such agents have not been fully investigated, particularly in models in which sensitization may be present. The aim of these studies was to evaluate the effects of the 5-HT(1B/1D) receptor agonist sumatriptan in specific models of pain states: a mouse model of inflammation-induced thermal hyperalgesia and a rat model of nerve injury-induced thermal hyperalgesia. In female mice, following intraplantar injection of carrageenan 225 min earlier, sumatriptan (300 microg/kg intraperitoneally; i.p.) increased paw withdrawal latency (PWL) from 3.1 +/- 0.4 s in the saline group to 5.6 +/- 0.9 s, measured 240 min postcarrageenan (P < 0.05 ANOVA followed by post hoc Dunnett's test). ⋯ The ability of sumatriptan to attenuate the carrageenan-induced reduction in PWL was blocked by the mixed 5-HT(1B/1D) receptor antagonist GR-127935 (3 mg/kg i.p.) but not by the 5-HT(1B) receptor antagonist SB-224289 (10 mg/kg i.p.). Sumatriptan had no effect on thermal hyperalgesia induced by sciatic nerve ligation in the rat at any time point. These data demonstrate that sumatriptan attenuates the hypersensitivity to noxious thermal stimuli induced by intraplantar carrageenan.
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Experimental neurology · Dec 2000
Plasticity in the rat spinal cord seen in response to lesions to the motor cortex during development but not to lesions in maturity.
Motor cortical inputs and proprioreceptive muscle afferents largely target the same spinal cord region. This study explored the idea that during development the two inputs interact via an activity-dependent mechanism to produce mature patterns of innervation. In rats, the forelimb motor cortex was ablated unilaterally at either postnatal day 7 (P7), the beginning of corticospinal synaptogenesis in the cervical cord, or at P50. ⋯ Also, the ratio of parvalbumin-positive neurons contralateral/ipsilateral to the developmental lesion (but not adult lesions) was decreased and the ratio of cJun-positive motoneurons increased. Thus, an early motor cortex lesion resulted in retention of a proportion of muscle afferent synapses to the ventral horn that are known to be lost during normal development. Parvalbumin and cJun are markers of neuronal activity suggesting that spinal circuitry develops permanently altered activity patterns in response to an early cortical lesion, although this plasticity is lost in the mature animal.