Experimental neurology
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Experimental neurology · Mar 1998
Comparative StudyComparison of more and less lipophilic serotonin (5HT1B/1D) agonists in a model of trigeminovascular nociception in cat.
The trigeminovascular system consists of bipolar neurons innervating pain-producing intracranial structures, such as the superior sagittal sinus (SSS), and projecting to the medullary and upper cervical dorsal horn second order neurons. Zolmitriptan is a newly developed 5HT1B/1D receptor agonist with both peripheral and central sites of action in the trigeminovascular system due to greater lipophilicity relative to the more hydrophilic antimigraine compound sumatriptan. Given that we have seen electrophysiological and autoradiographic binding data to suggest that the compound may inhibit activity at second-order neurons this study was designed to examine whether such an effect could be demonstrated in a population of trigeminal neurons using Fos immunohistochemistry. ⋯ We noted a significant reduction in Fos expression after treatment with zolmitriptan but no effect with sumatriptan. Given that zolmitriptan accesses central neurons and that the method of stimulation we have employed would bypass peripheral trigeminal mechanisms it is likely that the reduction in second-order trigeminal neuronal activity was due to a direct inhibitory effect of the compound on those cells. These neurons form a possible site for the treatment of acute attacks of migraine.
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Experimental neurology · Mar 1998
Extent of nociceptive dermatomes in adult rats is not primarily maintained by axonal competition.
Nociceptive innervation territories of individual peripheral and spinal nerves in the skin of the rat hind paw were investigated. In addition, the hypothesis that competitive interactions among the axons from adjacent dorsal root ganglia (DRG) play an important role in maintenance of dermatomal extent in adult animals was tested. The area of innervation territories of individual spinal and peripheral nerves was determined by nociceptive pinch test of the skin after extirpation of adjacent DRGs or transection of adjacent peripheral nerves, respectively. ⋯ Accordingly, we could find no autonomous innervation area of the sural nerve. Two weeks after extirpation of adjacent DRGs, the area of each of the isolated dermatomes L3, L4, and L5 increased only by about 10%, and it did not change detectably during the next 6 months. The results of our study (a) support the view that innervation fields supplied by the nociceptive (probably A delta) fibers are greater and display more overlap than those supplied by the C-fibers of the same nerve and (b) suggest that axonal competition for innervation territory is not decisive for maintenance of dermatomal borders in the adult rat.
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Experimental neurology · Jan 1998
A neuronal correlate of secondary hyperalgesia in the rat spinal dorsal horn is submodality selective and facilitated by supraspinal influence.
Tissue injury produces hyperalgesia not only in the injured area (primary hyperalgesia) but also outside of it (secondary hyperalgesia). In the present investigation, the submodality selectivity and the contribution of supraspinal influence to a neural correlate of the secondary hyperalgesia induced by neurogenic inflammation was studied in the presumed pain relay neurons of the rat spinal dorsal horn. Mechanically and thermally evoked responses to wide-dynamic range (WDR) neurons of the spinal dorsal horn were recorded under sodium pentobarbital anesthesia in rats. ⋯ The selective mechanical hyperexcitability in spinal WDR neurons, without a change in their spontaneous activity, can be explained by a heterosynaptic facilitatory action on presynaptic terminals mediating mechanical signals to these nociceptive spinal neurons. These findings indicate that brain stem-spinal pathways, involving the RVM, do not only suppress nociception but under some pathophysiological conditions concurrent facilitatory influence may predominate and lead to enhancement of mechanical hyperexcitability. The descending facilitatory feed-back loop to nociceptive spinal neurons may help to protect the wounded tissue and thus promote healing.
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Experimental neurology · Dec 1997
Muscle weakness, paralysis, and atrophy after human cervical spinal cord injury.
Muscle weakness and failure of central motor drive were assessed in triceps brachii muscles of individuals with chronic cervical spinal cord injury (SCI) and able-bodied controls. Electrical stimuli were applied to the radial nerve during rest and during triceps submaximal and maximal voluntary contractions (MVCs). The mean forces and integrated EMGs generated by SCI subjects during MVCs were significantly less than those produced by controls (P < 0.01), with 74 and 71% of muscles generating <10% control force and EMG, respectively. ⋯ Thus central motor drive was probably maximal to these muscles, and the force evoked during MVCs by below-lesion stimulation must come from activation of paralyzed muscle. SCI subjects also had significantly longer mean central nervous system (CNS) conduction times to triceps (P < 0.01) suggesting that the measured deficits reflect CNS rather than peripheral nervous system factors. Thus, the weak voluntary strength of these partially paralyzed muscles is not due to submaximal excitation of higher CNS centers, but results mainly from reduction of this input to triceps motoneurons.
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Experimental neurology · Dec 1997
Endogenous repair after spinal cord contusion injuries in the rat.
Contusion injuries of the rat thoracic spinal cord were made using a standardized device developed for the Multicenter Animal Spinal Cord Injury Study (MASCIS). Lesions of different severity were studied for signs of endogenous repair at times up to 6 weeks following injury. Contusion injuries produced a typical picture of secondary damage resulting in the destruction of the cord center and the chronic sparing of a peripheral rim of fibers which varied in amount depending upon the injury magnitude. ⋯ These cells may contribute to the development of cellular trabeculae that provide a scaffolding within the lesion cavity that provides the substrates for cellular infiltration and regeneration of axons. Together, these observations suggest that the endogenous reparative response to spinal contusion injury is substantial. Understanding the regulation and restrictions on the repair processes might lead to better ways in which to encourage spontaneous recovery after CNS injury.