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Biomedical subjects

R C Riley

Publications and source records attributed to R C Riley.

15 recordsLinked to original sources
PubMed2001

Presynaptic regulation of spinal cord tachykinin signaling via GABA(B) but not GABA(A) receptor activation.

Internalization of spinal cord neurokinin-1 receptors following noxious stimulation provides a reliable measure of tachykinin signaling. In the present study, we examined the contribution of GABAergic mechanisms to the control of nociceptor processing involving tachykinins. Spinal administration of the GABA(B) receptor agonist R(+)-baclofen in the rat, at antinociceptive doses, significantly reduced the magnitude of neurokinin-1 receptor internalization in neurons of lamina I in response to acute noxious mechanical or thermal stimulation. By contrast, administration of even high doses of the GABA(A) receptor agonists, muscimol or isoguvacine, were without effect. CGP55845, a selective GABA(B) receptor antagonist, completely blocked the effects of baclofen, but failed to increase the incidence of internalization when administered alone. These results provide evidence for a presynaptic control of nociceptive primary afferent neurons by GABA(B) but not GABA(A) receptors in the superficial laminae of the spinal cord, limiting tachykinin release. Because CGP5584 alone did not increase the magnitude of neurokinin-1 receptor internalization observed following noxious stimulation, there appears to be little endogenous activation of GABA(B) receptors on tachykinin-releasing nociceptors under acute stimulus conditions. The contribution of pre- and postsynaptic regulatory mechanisms to GABA(B) receptor-mediated antinociception was also investigated by comparing the effect of baclofen on Fos expression evoked by noxious stimulation to that induced by intrathecal injection of substance P. In both instances, baclofen reduced Fos expression not only in neurons that express the neurokinin-1 receptor, but also in neurons that do not. We conclude that baclofen acts at presynaptic sites to reduce transmitter release from small-diameter nociceptive afferents. Presynaptic actions on non-tachykinin-containing nociceptors could similarly account for the reduction by baclofen of noxious stimulus-induced Fos expression in neurokinin-1 receptor-negative neurons. However, the inhibition of Fos expression induced by exogenous substance P indicates that actions at sites postsynaptic to tachykinin- and/or non-tachykinin-containing primary afferent terminals must also contribute to the antinociceptive actions of GABA(B) receptor agonists.

Animals↗
PubMed1999

Immunohistochemical localization of GABA(B) receptors in the rat central nervous system.

The recent cloning of two gamma-aminobutyric acid(B) (GABA(B)) receptor isoforms (GABA(B)R1a/b), which are probably splice variants of the same gene transcript, allowed us to develop an antiserum that recognized the receptors in fixed tissue and to map their distribution in the rat central nervous system (CNS). We also investigated whether GABA(B)R1 colocalizes with glutamic acid decarboxylase (GAD), a marker of GABAergic cell bodies and terminals. Although GABA(B)R1-like immunoreactivity (GABA(B)R1-LI) was distributed throughout the CNS, several distinct distribution patterns emerged: (1) all monoaminergic brainstem cell groups appeared to contain very high levels of GABA(B)R1, (2) a very high intensity of GABA(B)R1-LI was observed in the majority of the cholinergic regions in the CNS, with exception of motoneurons of the third through sixth cranial nerve nuclei, and (3) a low density of the receptor was observed in most of the nuclei that contain cell bodies of GABAergic projection neurons. The highest GABA(B)R1 labeling was observed in the thalamus, interpeduncular nucleus and medial habenula. Cell bodies were labeled throughout the neuroaxis. We also observed dense neuropil labeling in many regions, suggesting that this receptor is localized in dendrites and/or axon terminals. However, in immunofluorescent double-labeling experiments for GABA(B)R1 and GAD, we never observed GABA(B)R1-LI in GAD-positive axon terminals; this result suggests that the GABA(B)R1 may not function as an autoreceptor. Double labeling was observed in the cell bodies of Purkinje neurons and in some interneurons. In general, the immunohistochemical localization of the GABA(B)R1 correlates well with physiologic and autoradiographic data on the distribution of GABA(B) receptors, but some critical differences were noted. Thus, it is likely that additional GABA(B) receptor subtypes remain to be identified.

Animals↗
PubMed1996

Spinal release of immunoreactive dynorphin A(1-8) with the development of peripheral inflammation in the rat.

Microprobes bearing immobilised antibodies to dynorphin A(1-8) were used to study the basal and evoked release of this prodynorphin derived peptide in the spinal cord of urethane anaesthetised normal rats and those with a peripheral inflammation. In the absence of any active peripheral stimulus the antibody microprobes detected immunoreactive (ir)-dynorphin A(1-8) in two areas (lamina I and laminae IV-V) in the dorsal horn of the spinal cord of normal rats. With the development of unilateral ankle inflammation over 3 to 5 days following subcutaneous injections of Freund's complete adjuvant, a basal presence of ir-dynorphin A(1-8) was found in both the dorsal and ventral horn regions of both sides of the spinal cord. Lateral compression of the ankles of the normal animals did not release ir-dynorphin A(1-8) during the period of stimulation, but this neuropeptide was detected in increased amounts in the ventral horn following the stimulus. By contrast, compression of inflamed ankles produced elevated levels of ir-dynorphin A(1-8) during the period of stimulus application at three major sites in the ipsilateral spinal grey matter. The largest peak was in the deep dorsal horn/upper ventral horn (laminae VI-VII), with further sites of significant release in the mid dorsal horn (laminae II-V) and the lower ventral horn. The observation that ir-dynorphin A(1-8) is physiologically released in the ventral and deep dorsal in addition to the superficial dorsal horn of the rat suggests an involvement of dynorphins in several aspects of spinal function.

Animals↗
PubMed1996

The burst-like firing of spinal neurons in rats with peripheral inflammation is reduced by an antagonist of N-methyl-D-aspartate.

Ankle inflammation was induced in rats by subcutaneous injection of complete Freund's adjuvant and the firing properties of spinal neurons receiving afferent input from the inflamed areas were studied four to six days later. Comparable neurons in normal rats were also studied. In normal animals the response of neurons to ankle compression consisted of a brief burst of action potentials followed by sustained firing during stimulus application. On cessation of the stimulus there was no prolonged afterdischarge. In rats with an inflamed ankle, compression of the ankle produced firing while the stimulus was applied, but with 17 of 22 neurons there was a prolonged (219 +/- 55 s) post-stimulus afterdischarge. All neurons studied in rats with peripheral inflammation fired with intermittent bursts of action potentials, particularly during the afterdischarge and spontaneous firing. The N-methyl-D-aspartate receptor antagonist DL-2-amino-5-phosphonopentanoate was ejected microiontophoretically near the cells studied. The major effect was a near abolition of bursts present in spontaneous firing and post-stimulus afterdischarges with a lesser reduction in firing during stimulus application. Effects on afterdischarge duration were variable. Since firing in bursts is known to increase transmitter release at some sites in the brain, it is proposed that when the relevant spinal neurons fire in bursts, additional intraspinal pathways are recruited and this contributes to the expanded receptive fields of neurons and possibly to the enhanced pain experienced by manipulation of inflamed peripheral tissues.

2-Amino-5-phosphonovalerate↗
PubMed1995

Afferent volley patterns and the spinal release of immunoreactive substance P in the dorsal horn of the anaesthetized spinal cat.

Microprobes bearing immobilized antibodies to the C-terminus of substance P were used to measure release of this neuropeptide in the spinal cord of the anaesthetized spinal cat in response to peripheral nerve stimulation. Release of substance P was just detectable in laminae I, II with 150 stimuli (0.5 Hz, 5 min) and was near maximal with 300 stimuli. Using two periods of stimulation of 10 min separated by 15 min, greater levels of substance P were detected during the second period. Fifteen to 25 min after two periods of peripheral nerve stimulation levels of substance P detected by microprobes were still elevated above those present prior to stimulation. Stimulation with bursts of three impulses when delivering a fixed number of stimuli resulted in detection of increased levels of substance P at sites adjacent to the areas of maximal release. The results suggest that maximal release of substance P from the central terminals of primary afferent fibres occurs with relatively few impulses and at low frequencies in agreement with what is known of release from the peripheral terminals of these fibres.

Afferent Pathways↗
PubMed1977

Computed tomography of the breast. A preliminary report.

Initial studies indicate that computed tomography can detect both benign and malignant breast disease in both fatty and dense, thick breasts. CT may also be capable of diagnosing early cancer or a precancerous lesion in women with dysplastic breasts or patients who have had radiation therapy or surgery, whereas some of these lesions cannot be diagnosed by mammography because the breast is too dense.

Breast Diseases↗
PubMed1977

A new low dose mammography technique.

Reduction of radiation dosage to patients undergoing mammography is very important, especially when large-scale screening projects for early detection of breast carcinoma are considered. A new low dose mammographic technique employing Kodak XG film and Industrex F2 intensifying screen in a vacuum package has been evaluated in 533 patients. This Kodak system was found to provide excellent diagnostic quality image, and to be an acceptable technique for mammography.

Breast Neoplasms↗
PubMed1976

Film mammography: new low radiation technology.

A new mammographic technique with Kodak MIN-R film and a Kodak MIN-R screen in a vacuum package has been evaluated in 607 cases. Direct mammographic comparison is made with the Du Pont Lo-dose system in the first 101 patients. The system provides excellent diagnostic quality images with at least a two-fold reduction in patient exposure compared to other current mammographic techniques.

Female↗