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Biomedical subjects

A K Jones

Publications and source records attributed to A K Jones.

At least 37 records · Page 2Linked to original sources
PubMed1999

Measurement of changes in opioid receptor binding in vivo during trigeminal neuralgic pain using [11C] diprenorphine and positron emission tomography.

The binding of [11C]diprenorphine to mu, kappa, and delta subsites in cortical and subcortical structures was measured by positron emission tomography in vivo in six patients before and after surgical relief of trigeminal neuralgia pain. The volume of distribution of [11C]diprenorphine binding was significantly increased after thermocoagulation of the relevant trigeminal division in the following areas: prefrontal, insular, perigenual, mid-cingulate and inferior parietal cortices, basal ganglia, and thalamus bilaterally. In addition to the pain relief associated with the surgical procedure, there also was an improvement in anxiety and depression scores. In the context of other studies, these changes in binding most likely resulted from the change in the pain state. The results suggest an increased occupancy by endogenous opioid peptides during trigeminal pain but cannot exclude coexistent down-regulation of binding sites.

Aged↗
PubMed1998

Pain and Stroop interference tasks activate separate processing modules in anterior cingulate cortex.

Investigations of pain using functional imaging techniques have revealed an extensive central network associated with nociception. This network includes the thalamus, insula, prefrontal cortex and anterior cingulate cortex (ACC) as well as the somatosensory cortices. Positron emission tomography (PET) of regional cerebral blood flow (rCBF) has demonstrated activation of the ACC during cognitively challenging tasks such as the Stroop interference task and divided attention. One interpretation of this research is that ACC is involved in the general features of attention and that it does not play a specific role in pain processing per se. Three-dimensional PET imaging provides a method for assessments of rCBF in a single individual during multiple tasks. In addition, coregistration of PET and magnetic resonance (MR) images allows for better localisation of the PET signals so that differences in cortical activation sites can be more accurately determined. This approach was used to assess rCBF during the experience of pain by subtracting images collected during heat from those during noxious heat stimulation. Two regions of the ACC had elevated rCBF, one in the perigenual region and one in the mid-rostrocaudal region (i.e. midcingulate cortex). During the execution of the Stroop task, the group result showed the midcingulate region overlapping with the site seen during the experience of pain. This group result, however, was not confirmed in the individual subject analysis, which revealed widespread and independent areas of ACC response to pain and Stroop. It is concluded that the ACC contributes to multiple cognitive procedures. It is inadequate to describe the primary contribution of ACC to pain processing as "attention" because it is unlikely that the multiple small and independent activation sites produced by pain and Stroop subserve attentive processing throughout the brain.

Adult↗
PubMed1998

Cerebral responses to a continual tonic pain stimulus measured using positron emission tomography.

We have previously demonstrated the localised positron emission tomographic cerebral correlates of the experience of painful phasic heat in the normal human brain. In this study we examine whether these responses are different using a continuous, tonic heat stimulus. The regional cerebral responses to non-painful and painful thermal stimuli in 12 male subjects were studied by monitoring serial measurements of regional cerebral blood flow (rCBF) with positron emission tomography (PET) using H2(15)O. Significantly increased rCBF responses to tonic noxious stimulation compared with non-noxious stimulation were observed bilaterally in the anterior cingulate (Brodmann's area (BA) 24) cortex. Contralateral responses were observed in the lentiform nucleus and posterior insula cortex and ipsilateral responses were observed in the thalamus, cerebellum, prefrontal (BA 10) cortex and anterior insula cortex. These findings demonstrate general agreement between the main areas of cerebral activation during both phasic and tonic pain.

Adult↗
PubMed1998

Experiences with functional magnetic resonance imaging at 1 tesla.

Functional magnetic resonance imaging (fMRI) has been performed on a standard 1 T system using a pulse sequence developed to utilize blood oxygen level dependent (BOLD) contrast and an off-line analysis routine using correlation techniques. The sequence and the data analysis routine have been validated by reproducing the conventional hand movement paradigm studies reported by numerous other workers. Our work has then been extended to investigate cerebral foci for a tonic pain stimulus and the cortical representation of oesophageal stimulation. Both these studies relate to paradigms where the expected BOLD signal is significantly less than that encountered for motor or visual cortex paradigms. The results show good agreement with other modalities (positron emission tomography, magnetoencephalography and cortical evoked potentials). Performing fMRI at 1 T is slightly controversial. However, our successful study of demanding paradigms, using a standard clinical 1 T imaging system, has important implications for many other users operating at this field strength.

Brain↗
PubMed1997

Identification of human brain loci processing esophageal sensation using positron emission tomography.

BACKGROUND & AIMS: Brain loci that process human esophageal sensation remain unidentified. The aim of this study was to identify the brain loci that process nonpainful and painful human esophageal sensation. METHODS: In 8 healthy subjects (7 men; age range, 24-47 years), distal esophageal stimulation was performed by repeatedly inflating a balloon at volumes that produced either no sensation, definite sensation, or pain. Two positron emission tomography scans were performed for each sensation using H2(15)O. Magnetic resonance brain scans were also performed in each subject, and the positron emission tomography data were coregistered with magnetic resonance scans. Analysis of covariance-corrected t images showing the contrasts definite sensation-baseline, pain-baseline, and pain-definite sensation were created. RESULTS: Nonpainful stimulation elicited bilateral activations along the central sulcus, insular cortex, and frontal/parietal operculum (P < 0.01). Painful stimulation produced more intense activations of the same areas and additional activation of the right anterior insular cortex and the anterior cingulate gyrus. Multiple areas of decreased activation were also observed; prominent among these was the right prefrontal cortex, which was inhibited during both nonpainful and painful stimulation. CONCLUSIONS: Esophageal sensation activates bilaterally the insula, primary somatosensory cortex, and operculum. The right anterior insular cortex and anterior cingulate gyrus process esophageal pain.

Adult↗
PubMed1997

Primary care management of acute low back pain.

Acute low back pain will affect more than 80% of the population, with more than 28% of the industrial workforce suffering from lost work. Acute low back pain is recognized as the third most common illness presenting to private practice groups. The psychosocial overtones of depression and anxiety that often coexist or predate the episode of acute low back pain add to its complexity and cost. Diagnosis and treatment options are reviewed based on the Agency for Health Care Policy and Research recommendations of 1994. This article reviews details of the history and physical with emphasis on the importance of a thorough neurologic and psychologic evaluation. "Red flags" that should warn the clinician of the presence of a more acute illness are discussed with recommendations for referral. The treatment of acute low back pain now centers on increasing mobility and functional use of the spine as soon as possible. Nonsteroidal anti-inflammatory agents as well as aspirin and acetaminophen are recommended as first-line drug treatments; they have been found to be equally as effective as muscle relaxants and opioids for the control of pain without the burden of dependence and potential for abuse.

Acute Disease↗
PubMed1997

Reduced cortical responses to noxious heat in patients with rheumatoid arthritis.

OBJECTIVES: To test the hypothesis that patients with chronic inflammatory pain develop adaptive cortical responses to noxious stimulation characterised by reduced anterior cingulate responses. METHODS: Positron emission tomography was used to measure changes in regional cerebral blood flow (rCBF) in response to an acute experimental pain stimulus in six patients with rheumatoid arthritis (RA) in comparison to six age and sex matched controls. A standardised and reproducible non-painful and painful phasic heat stimulus was delivered by a thermal probe to the back of the right hand during six two minute periods during which time rCBF measurements were made. The effects of non-painful heat were subtracted from those of painful heat to weight the analysis towards the non-discriminatory or 'suffering' components of pain processing. Significance maps of pain processing were generated and compared in each group and contrasted with results obtained in a group of patients with atypical facial pain (AFP) that have been previously published. RESULTS: The RA patients showed remarkably damped cortical and subcortical responses to pain compared with the control group. Significant differences between the two groups were observed in the prefrontal (BA 10) and anterior cingulate (BA 24) and cingulofrontal transition cortical (BA 32) areas. The reduced anterior cingulate responses to standardised heat pain were compared with the increased cingulate responses seen in patients with psychogenically maintained pain (AFP) who had both lower pain tolerance and mood than the RA group. CONCLUSIONS: Major cortical adaptive responses to standardised noxious heat can be measured and contrasted in patients with different types of chronic pain. The different pattern of cingulate and frontal cortical responses in the patients with inflammatory and non-nociceptive pain suggest that different mechanisms are operating, possibly at a thalamocortical level. Implications for treatment strategies for chronic pain are discussed.

Adaptation, Physiological↗
PubMed1996

Comparison of the effects of cyclic AMP analogues on cholesterol metabolism in cultured rat and hamster hepatocytes.

The effects of two cell-permeable cyclic AMP analogues, 8-chloro cyclic AMP (8-Cl cAMP) and 8-(4-chlorophenylthio) cyclic AMP (8-CPT cAMP), on cholesterol esterification, cholesteryl ester hydrolysis and bile acid synthesis were compared in cultured rat and hamster hepatocytes. Cholesterol esterification, as measured by the incorporation of [3H]oleate into cholesteryl ester, was increased by 58-88% by the analogues in rat hepatocytes and by 33-43% in hamster cells. The response in rat hepatocytes, however, was observed after a relatively short incubation time (28% increase after 1 hr), whereas that in hamster cells required a longer period (36% after 12 hr) to become apparent. The activity of the cytosolic neutral cholesteryl ester hydrolase in rat hepatocytes was also stimulated by both cyclic AMP analogues (31-37%, but the microsomal activity was unaffected. In hamster hepatocytes, however, microsomal cholesteryl ester hydrolase activity was increased (47-80%) in the presence of 8-Cl cAMP or 8-CPT cAMP. Bile acid synthesis was increased by 8-CPT cyclic AMP in rat cells (approximately 25%) but was unchanged by both analogues in hamster hepatocytes. These results indicate significant differences in the way in which cholesterol metabolism responds to cyclic AMP in cultured rat and hamster hepatocytes.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1996

Noninvasive quantification of rCBF using positron emission tomography.

This study proposes a new method for the pixel-by-pixel quantification of regional CBF (rCBF) with positron emission tomography and H(15)(2)O by using a reference tissue region. No arterial blood is required. Simulation studies revealed that the calculation of rCBF was fairly stable provided that the frame time was relatively short compared with total scan time. In practice, calculated CBF images correlated significantly with those obtained with the dynamic/integral method. Because the method accurately detects changes in CBF, it is particularly suitable for brain activation studies.

Adult↗
PubMed1996

Pain processing in four regions of human cingulate cortex localized with co-registered PET and MR imaging.

Neurosurgical and positron emission tomography (PET) human studies and animal electrophysiological studies show that part of the anterior cingulate cortex (ACC) is nociceptive. Since the contribution of the ACC to pain processing is poorly understood, this study employed PET and magnetic resonance (MR) image co-registration in grouped and individual cases to locate regions of altered relative regional cerebral blood flow (rCBF). Seven right-handed, neurologically intact males were subjects; each received neuropsychological and pain threshold testing. Subjects were scanned during infusion of H2[15O]: four randomized scans during innocuous heat stimulation to the back of the left hand and four scans during noxious but bearable heat to the same place. The averaged rCBF values during innocuous stimuli were subtracted from those during noxious stimuli and statistical parametric maps (SPMs) for the group were computed to identify regions of altered relative rCBF. Finally, single-subject PET images of elevated and reduced rCBF were co-registered with MR images and projected onto reconstructions of the medial surface of the hemisphere. The SPM analysis of the group showed one site with elevated rCBF in the midcingulate cortex and one in the perigenual cortex predominantly contralateral to the side of stimulation. There were bilateral sites of reduced rCBF in the cingulofrontal transitional cortex and in the posterior cingulate cortex (PCC). Co-registered PET and MR images for individuals showed that only one case had a single, large region of elevated rCBF, while the others had a number of smaller regions. Six cases had at least one significant elevation of rCBF in the right hemisphere that primarily involved area 24b'; five of these cases also had an elevation in area 32', while the seventh case had elevated rCBF in these areas in the left hemisphere. The rostral site of elevated rCBF in the group was at the border of areas 24/24' and areas 32/32' although most cases had a site of elevation more rostral in the perigenual cingulate cortex. The ACC site of reduced rCBF was in areas 8 and 32 and that in the PCC included much of areas 29/30 in the callosal sulcus, areas 23b and 31 on the cingulate gyral surface and parietal area 7m. The localization of relative rCBF changes suggests different roles for the cingulate cortex in pain processing: (i) elevated rCBF in area 24' may be involved in response selection like nocifensive reflex inhibition; (ii) activation of the perigenual cortex may participate in affective responses to noxious stimuli like suffering associated with pain; and (iii) reduced rCBF in areas 8 and 32 may enhance pain perception in the perigenual cortex, while that in the PCC may disengage visually guided processes.

Adult↗
PubMed1995

Effects of IZP-94005 (contignasterol) on antigen-induced bronchial responsiveness in ovalbumin-sensitized guinea-pigs.

1. We have investigated the novel naturally occurring marine compound, IZP-94005 (contignasterol), as a potential anti-asthma agent, using both in vivo and in vitro models of allergen-induced bronchoconstriction and airway smooth muscle contraction. 2. Tracheal rings from ovalbumin (OA)-sensitized guinea-pigs were treated with various concentrations of IZP-94005 for 20 min prior to challenge with ovalbumin. IZP-94005 (3-30 microM) inhibited responses of sensitized tracheal rings stimulated with OA in a concentration-dependent manner, with an IC50 of 10 microM. 3. IZP-94005 (10 microM) had no effect on carbachol-induced contractions of sensitized guinea-pig tracheal rings, although it did inhibit histamine-induced responses of OA sensitized guinea-pig tracheal rings. 4. The effects of IZP-94005 in vivo were examined using OA-sensitized guinea-pigs which were tracheotomized under anaesthesia and placed in a body plethysmograph. Measurements of lung resistance and compliance were performed by isovolumetric analysis of volume and trans-pulmonary pressure. 5. IZP-94005 (50 and 200 micrograms kg-1), by inhalation 20 min prior to OA challenge caused significant inhibition of the increase in lung resistance induced by OA in sensitized guinea-pigs, compared to vehicle-treated animals. Nedocromil sodium (20 mg kg-1), with a similar protocol, also inhibited OA-induced responses in this model. 6. We therefore suggest that IZP-94005 is a good candidate for further investigation as a possible antiasthma agent.

Administration, Inhalation↗
PubMed1994

Quantitation of [11C]diprenorphine cerebral kinetics in man acquired by PET using presaturation, pulse-chase and tracer-only protocols.

The quantitation of regional cerebral in vivo opioid receptor rate constants using [11C]diprenorphine and positron emission tomography (PET) using 3 types of protocol (presaturation, pulse-chase naloxone displacement and tracer-only protocols) together with measurements of regional cerebral blood flow is described in normal volunteers. Arterial blood was sampled continuously for radioactivity and was corrected for metabolites and plasma/blood partition of radioactivity to provide a continuous plasma input function. A compartmental model involving 3 tissue compartments was used to describe the regional cerebral pharmacokinetics of the tracer. The compartments comprised: (1) free plus rapidly exchanging non-specifically bound ligand, (2) specifically bound, naloxone displaceable ligand, and (3) a kinetically distinguishable non-specifically bound pool. Regional estimates of fractional rate constants relating to specific binding were obtained using naloxone in a pulse-chase design of tracer displacement. Less precise estimates of these rate constraints were obtained from single-tracer-only studies, but when binding was expressed as the tissue total volume of distribution relative to plasma there was good correlation with regional values obtained from pulse-chase studies performed in the same individuals. The application of these protocols to the measurement of indices of regional-specific opioid receptor binding in the human brain is discussed.

Adult↗
PubMed1994

Changes in central opioid receptor binding in relation to inflammation and pain in patients with rheumatoid arthritis.

A group of four patients with RA were examined to test the hypothesis that there is a change in the endogenous opioid system in the brain during inflammatory pain. Regional cerebral opioid receptor binding was quantified using the opioid receptor antagonist [11C] diprenorphine and positron emission tomography (PET). In the four patients studied in and out of pain, significant increases in [11C]diprenorphine binding were seen in association with a reduction in pain. Increases were seen in most of the areas of the brain that were sampled apart from the occipital cortex. Significant region-specific increases over and above the more generalized changes were also seen in the frontal, cingulate and temporal cortices in addition to the straight gyrus. These findings are consistent with the hypothesis that there are substantial increases in occupancy by endogenous opioid peptides during inflammatory pain.

Arthritis, Rheumatoid↗