Brain research
-
The periaqueductal gray matter (PAG) serves as the midbrain link between forebrain emotional processing systems and motor pathways used in the defense reaction. Part of this response depends upon PAG efferent pathways that modulate cardiovascular-related sympathetic outflow systems, including those that regulate the heart. While it is known that the PAG projects to vagal preganglionic neurons, including possibly cardiovagal motoneurons, no information exists on the PAG circuits that may affect sympathetically mediated cardiac functions and, thus, the purpose of this study was to use neuroanatomical methods to identify these pathways. ⋯ Both serotonergic and non-serotonergic sympathetic premotor neurons in these two regions receive inputs from the PAG. Weak PAG projections to sympathetic premotor neurons were found in the rostral ventrolateral medulla (including to C1 adrenergic neurons), locus coeruleus, A5 cell group, paraventricular and lateral hypothalamic nuclei. In summary, both the lateral and ventrolateral PAG columns appear to be capable of modulating cardiac sympathetic functions via a series of indirect pathways involving sympathetic premotor neurons found in selected sites in the hypothalamus, midbrain, pons, and medulla oblongata, with the major outflow terminating in bulbospinal regions of the rostral ventromedial medulla.
-
Rats were kindled by repeated injections of pentylenetetrazole (PTZ; 37.5 mg/kg; i.p.) in the presence or absence of the opioid receptor antagonist naloxone. Naloxone (10 mg/kg; i.p.) applied 30 min before each PTZ application had no major effect on the seizure development, although a slight decrease in the seizure expression of fully kindled animals could be observed. In the kindled animals, a pronounced but transient increase in c-fos mRNA level was observed in several brain areas after the injection of PTZ. ⋯ Brosz, Naloxone ameliorates the learning deficit induced by pentylenetetrazole kindling in rats, Eur. J. Neurosci. 6 (1994) 1512-1515].
-
Intrathecal injection of a nitric oxide releasing compound, NOC-18, was used to define the role of nitric oxide (NO) in the spinal mechanism of neuropathic pain caused by unilateral chronic constriction injury to rat sciatic nerves. Paw withdrawal latency was used to evaluate nociception induced by thermal stimuli before surgery and afterwards at 1, 3, and 6 h, and on days 1, 2, 3, 4, 5, 8, and 12 after the nerve ligature. In the sham-surgery control groups, intrathecal injection of 10 or 100 microg of NOC-18 did not produce any change in withdrawal latencies. ⋯ The effects of intrathecal injection of MK-801, a N-methyl-D-aspartate (NMDA) receptor antagonist, N-nitro-L-arginine methyl ester (L-NAME), a NO synthase inhibitor, methylene blue (MB), a soluble guanylate cyclase inhibitor, and hemoglobin (Hb), a NO scavenger, on the development of thermal hyperalgesia after the sciatic nerve ligature were examined in the presence and absence of 1 and 10 microg of NOC-18. Acceleration of the development of thermal hyperalgesia induced by 1 and 10 microg NOC-18 was completely inhibited by Hb, but was not affected by either MK-801, L-NAME or MB. These findings indicate that NO plays an important role in the rapid development of thermal hyperalgesia after the nerve injury, but that facilitation of nociceptive processing in the spinal cord may entail an alternate to the NO-cyclic guanosine 3',5'-monophosphate (cGMP) pathway.
-
Clinical Trial Controlled Clinical Trial
Correlation between local vascular and sensory changes following tissue inflammation induced by repetitive application of topical capsaicin.
The aim of the present study was to investigate local vascular and sensory changes and their correlation in order to obtain a better understanding of the mechanisms of allodynia, hyperalgesia and vascular changes following tissue inflammation induced by repetitive application of capsaicin cream. This type of application was utilized as a controlled model of inflammation which was altered in intensity due to its repetitive applicability. Ten healthy volunteers participated in two experiments separated by at least five days. ⋯ Compared to placebo, the first application of capsaicin cream also resulted in an increased blood-flow, elevated temperature and visible flare. The highest values of these sensory and vascular parameters were reached after the third application. A direct correlation between visible flare, secondary mechanical hyperalgesia and allodynia following repetitive application of capsaicin indicates that both common central and peripheral mechanisms were involved in these changes.
-
The objective of this study was to determine whether the duration of an ischemic insult effects the activity of the mitochondrial enzyme pyruvate dehydrogenase (PDH) in relation to the recovery of metabolites and regional cerebral blood flow (rCBF) immediately after ischemia and during reperfusion in gerbil cortex. Cerebral ischemia was induced, using the bilateral carotid artery occlusion method, for 20 or 60 min, followed by reperfusion up to 120 min. Immediately after ischemia PDH activity increased threefold regardless of ischemic duration. ⋯ Recovery of metabolism after reperfusion did not parallel the changes in rCBF in either group, most noticeably in the 60-min ischemic group. The slow normalization of PDH activity reflected the poor recovery of metabolites in the 60-min ischemic group, indicating that PDH activity is important in the resynthesis of energy metabolites during reperfusion. In conclusion, prolonging the ischemic insult effected PDH activity during reperfusion, impaired recovery of energy metabolites, and worsened the recovery of rCBF.