Biomedical subjects

Thomas J Morrow

Publications and source records attributed to Thomas J Morrow.

12 recordsLinked to original sources

PubMed2006

In vivo imaging of functional disruption, recovery and alteration in rat olfactory circuitry after lesion.

Compensatory changes following disruption of neuronal circuitry have been indicated by previous imaging studies of stroke and other brain injury, but evidence of the pathways involved in such dynamic changes has not been shown in vivo. We imaged rats before and after lesion-induced disruption of the lateral olfactory tract to investigate the subsequent recovery and/or reorganization of functional neuronal circuitry. Serial magnetic resonance imaging was performed following intranasal administration of a paramagnetic track tracer Mn(2+). Images were analyzed using statistical mapping techniques in the stereotactic coordinate system. At 1 week post-lesion, Mn(2+) transport caudal to lesion was reduced as expected, and more importantly, increased transport through the anterior commissure was seen. At 4 weeks post-lesion, there was recovery of transport caudal to lesion, and increased transport through the anterior commissure extended to the contralateral olfactory cortex. Correlation analysis of regional Mn(2+) transport indicated that contralateral enhancement was not simply due to septal window spillover. This study demonstrates for the first time in vivo evidence of compensatory changes in functional neuronal activity to a contralateral pathway through the commissure following brain injury.

Administration, Intranasal↗

PubMed2006

Clonidine effects on pain evoked SII activity in humans.

We investigated pain evoked activity in the human secondary sensory cortex (SII) following clonidine administration in six healthy volunteers using multi-channel magnetoencephalography (MEG). Pain was elicited by electrical shocks applied intracutaneously to the fingertip. Subjects rated pain intensity and perceptions of tiredness and passiveness by numerical ranking scales. Each subject underwent two investigations, one week apart from each other, with clonidine doses of 1.5 or 3.0microg/kg, administered intravenously in a random order and double-blinded. We applied a total number of seven blocks, each consisting of 60 painful stimuli, with one adaptation block, one pre-medication block, four post-medication blocks and one recovery block at the end of the session. MEG data were analysed by dipole reconstruction using CURRY(R) (Neuroscan, Hamburg) software package. Cortical activity in the contralateral SII cortex appeared with peak latencies of 118.5+/-10ms. This activity was significantly reduced by clonidine, in parallel with a reduction of pain intensity and enhancement of subjective tiredness and passiveness. There was, however, no significant correlation between MEG and subjective effects. Although both clonidine doses had similar effects, the higher dose induced longer changes. Results indicate that intravenous clonidine is able to relieve pain, but the exact mechanism of clonidine at the level of the SII cortex remains unclear. It is possible that clonidine interacts with the brainstem ascending system regulating vigilance and arousal which would explain the observed decrement of pain induced activity in SII. An additional more specific analgesic action at spinal level cannot be excluded.

Adrenergic alpha-Agonists↗

PubMed2005

Differences in forebrain activation in two strains of rat at rest and after spinal cord injury.

Forebrain activation patterns in normal and spinal-injured Sprague-Dawley (SD) rats were determined by measuring regional cerebral blood flow as an indicator of neuronal activity. Data are compared to our previously published findings from normal and spinal-injured Long-Evans (LE) rats and reveal a striking degree of overlap, as well as differences, between strains in the basal (unstimulated) forebrain activation in normal animals. Specifically, 81% of the structures sampled showed similar activation in both strains, suggesting a consistent and identifiable pattern of basal cerebral activation in the rat. LE controls showed significantly greater basal activation in the remaining structures compared to SD control group, including the anterior dorsal thalamus, basolateral amygdala, SII cortex, and the hypothalamic paraventricular nucleus. In contrast, spinal cord injury (SCI) resulted in strain-specific changes in forebrain activation categorized by structures that showed significant increases in: (1) only LE SCI rats (posterior, ventrolateral, and ventroposterolateral thalamic nuclei); (2) only SD SCI rats (anterior-dorsal and medial thalamus, basolateral amygdala, cingulate and retrosplenial cortex, habenula, interpeduncular nucleus, hypothalamic paraventricular nucleus, periaqueductal gray); or (3) both strains (arcuate nucleus, ventroposteromedial thalamus, SI and SII somatosensory cortex). These results provide information related to the remote, i.e. supraspinal, effects of spinal cord injury and suggest that genetic differences play an important part in the forebrain response to such injury. Brain activation studies therefore provide a useful tool in understanding the full extent of secondary consequences following spinal injury and for identifying potential central mechanism responsible for the development of pain.

Animals↗

PubMed2004

Early painful diabetic neuropathy is associated with differential changes in tetrodotoxin-sensitive and -resistant sodium channels in dorsal root ganglion neurons in the rat.

Diabetic neuropathy is a common form of peripheral neuropathy, yet the mechanisms responsible for pain in this disease are poorly understood. Alterations in the expression and function of voltage-gated tetrodotoxin-resistant (TTX-R) sodium channels have been implicated in animal models of neuropathic pain, including models of diabetic neuropathy. We investigated the expression and function of TTX-sensitive (TTX-S) and TTX-R sodium channels in dorsal root ganglion (DRG) neurons and the responses to thermal hyperalgesia and mechanical allodynia in streptozotocin-treated rats between 4-8 weeks after onset of diabetes. Diabetic rats demonstrated a significant reduction in the threshold for escape from innocuous mechanical pressure (allodynia) and a reduction in the latency to withdrawal from a noxious thermal stimulus (hyperalgesia). Both TTX-S and TTX-R sodium currents increased significantly in small DRG neurons isolated from diabetic rats. The voltage-dependent activation and steady-state inactivation curves for these currents were shifted negatively. TTX-S currents induced by fast or slow voltage ramps increased markedly in neurons from diabetic rats. Immunoblots and immunofluorescence staining demonstrated significant increases in the expression of Na(v)1.3 (TTX-S) and Na(v) 1.7 (TTX-S) and decreases in the expression of Na(v) 1.6 (TTX-S) and Na(v)1.8 (TTX-R) in diabetic rats. The level of serine/threonine phosphorylation of Na(v) 1.6 and In Na(v)1.8 increased in response to diabetes. addition, increased tyrosine phosphorylation of Na(v)1.6 and Na(v)1.7 was observed in DRGs from diabetic rats. These results suggest that both TTX-S and TTX-R sodium channels play important roles and that differential phosphorylation of sodium channels involving both serine/threonine and tyrosine sites contributes to painful diabetic neuropathy.

Anesthetics, Local↗

PubMed2003

Designing and implementing an effective specialty pharmacy service program.

The universe of high-tech biologic medications is expanding rapidly, and health plans are struggling to control the rising costs associated with the use of these agents. Specialty pharmaceutical networks are gaining greater visibility as a helpful tool in this effort. The author describes how to write the request for proposal and begin the decision-making and implementation processes for specialty pharmacy services.

Biotechnology↗

PubMed2002

A unique representation of heat allodynia in the human brain.

Skin inflammation causes innocuous heat to become painful. This condition, called heat allodynia, is a common feature of pathological pain states. Here, we show that heat allodynia is functionally and neuroanatomically distinct from normal heat pain. We subtracted positron emission tomography scans obtained during painful heating of normal skin from scans during equally intense but normally innocuous heating of capsaicin-treated skin. This comparison reveals the specific activation of a medial thalamic pathway to the frontal lobe during heat allodynia. The results suggest that different central pathways mediate the intensity and certain qualitative aspects of pain. In making this differentiation, the brain recognizes unique physiological features of different painful conditions, thus permitting adaptive responses to different pain states.

Adult↗

PubMed2002

Long-term changes in behavior and regional cerebral blood flow associated with painful peripheral mononeuropathy in the rat.

We identified long-term (up to 12 weeks), bilateral changes in spontaneous and evoked pain behavior and baseline forebrain activity following a chronic constriction injury (CCI) of the sciatic nerve. The long-term changes in basal forebrain activation following CCI were region-specific and can be divided into forebrain structures that showed either: (1) no change, (2) an increase, or (3) a decrease in activity with regard to the short-term (2 weeks) changes we previously reported. All the rats showed spontaneous pain behaviors that persisted throughout the 12-week observation period, resembling the pattern of change found in four limbic system structures: the anterior dorsal thalamus, habenular complex, and the cingulate and retrosplenial cortices. In contrast, heat hyperalgesia was delayed in onset until 4 weeks following CCI, but then persisted, showing a nearly constant level of increased responsiveness. The forebrain activation that resembles this behavioral pattern of change is found in somatosensory cortex, and in the hypothalamic paraventricular nucleus and the basolateral amygdala. Finally, mechanical allodynia, which was maximal during the first 2 weeks following nerve injury and gradually recovered by the seventh post-operative week uniquely matches the time course of changes in ventrolateral and ventroposterolateral thalamic activity. Our results indicate that peripheral nerve damage results in persistent changes in behavior and resting forebrain systems that modulate pain perception. The persistent abnormalities in the somatosensory cortex and thalamus suggest that the sensory thalamocortical axis is functionally deranged in certain chronic pain states.

Animals↗

PubMed2002

Anemia of cancer in intermediate-grade non-Hodgkin's lymphoma.

BACKGROUND: Current literature suggests that anemia at baseline is an important adverse prognostic factor for lymphoma-related outcomes. We evaluated the prevalence, risk factors, and prognostic value of anemia in patients with intermediate-grade non-Hodgkin's lymphoma (IGNHL) treated in a community-based practice. METHODS: The retrospective sample included 591 patients who had IGNHL diagnosed between 1993 and 1999 and who were subsequently treated with CHOP chemotherapy. Anemia was defined as a hemoglobin (Hb) value < 12 g/dL. RESULTS: Anemia was present in 193 of 546 patients (35.3%). Baseline anemia was significantly associated with age > 60, extranodal sites > or = 2, Ann Arbor stage III or IV, elevated lactate dehydrogenase (LDH) level, B symptoms, and histology type. Baseline Hb was also a significant predictor of nonresponse to chemotherapy. CONCLUSIONS: Our study results support previous findings of a high prevalence of anemia in cancer patients before cytotoxic therapy and the adverse impact that baseline anemia has on response to chemotherapy.

Aged↗

PubMed1996

Medial frontal cortex lesions selectively attenuate the hot plate response: possible nocifensive apraxia in the rat.

Lesions in the cingulate cortex have attenuated pain-related behavior in humans. We wished to evaluate an animal model of this effect by studying the effects of bilateral lesions within the medial frontal cortex, including rat cingulate cortex, on performance in 3 behavioral tests: the formalin, hot-plate, and tail-flick tests. Average hot-plate latencies, but not formalin test scores or tail-flick latencies, were significantly increased by an average of 82% in rats with medial frontal cortex lesions, as compared to sham-operated control rats. Motor function, as tested by righting and foot lifting responses and clinical observation, was not impaired. No effects were seen on hot-plate latencies, tail-flick latencies, and formalin pain scores in sham-operated rats. These results suggest that the medial frontal cortex of the rat mediates certain types of supraspinally organized responses to noxious heat pain. Lesions that include the medial frontal and anterior cingulate cortex appear to disrupt the integration of increasing heat nociceptive input with motor responses that are necessary to execute quickly the escape behavior in the hot-plate test.

Animals↗

PubMed1994

Central delay of the laser-activated rat tail-flick reflex.

The latency of the heat-activated rat tail-flick (TF) reflex is dependent upon 4 variables, none of which has previously been determined: activation of cutaneous nociceptors (TN); afferent conduction to the dorsal horn (TA); conduction within the central nervous system (CNS) (central delay); and conduction from the ventral horn (VH) to, and activation of, tail muscles (TE). Using a CO2 infrared laser (10 W, 45 msec) to produce synchronous activation of tail-skin nociceptors, TF latency (EMG response) was measured in 10 awake rats. Based on shifts in response latency from points of stimulation near the tip and base of the tail, conduction velocity in the afferent limb of the reflex was estimated to be 0.76 +/- 0.11 m/sec. This indicates that the response is mediated by C fibers. The rats were then anesthetized with pentobarbital and multiple-unit activity and evoked potentials (EPs) were recorded from the superficial dorsal horn at spinal segments S3-CO1 during laser or high-intensity electrical (10 mA, 1 msec) stimulation of the tail. Unit activity and EPs elicited by both stimuli consisted of two distinct components, corresponding to activation of A and C fibers. The difference in latency between laser and electrical evoked activity indicated that 60.00 +/- 7.33 msec was required for activation of nociceptors by the laser. Electrical stimulation of the VH at S3-CO1 in 3 rats produced a TF (EMG) response in 4 msec. Central delay, calculated as total TF time minus (TN+TA+TE), was 82.3 +/- 13.08 msec. This represents the time frame during which modulation of the reflex by an intrinsic, pain-activated, supraspinal system could occur.

Animals↗

PubMed1988

Cutaneous pain and detection thresholds to short CO2 laser pulses in humans: evidence on afferent mechanisms and the influence of varying stimulus conditions.

Pain and detection thresholds to short CO2 laser pulses were studied in healthy human subjects. Pain thresholds were significantly higher than detection thresholds in both hairy and glabrous skin; in the glabrous skin both thresholds were higher in the hairy skin. The range from detection threshold to pain threshold was larger in the glabrous skin. The minimal energy per surface area needed to produce any sensation (detection) or pain sensation decreased with increasing stimulus surface, and this spatial summation effect was to equal magnitude in the hairy and the glabrous skin. With decreasing stimulus pulse duration (from 45 to 15 msec) the detection and pain thresholds were elevated: this effect was stronger on pain thresholds. With increasing adapting skin temperature, less energy was needed to produce any sensation (detection) or pain sensation. The effect of adapting skin temperature was equal on pain and detection thresholds. The conduction velocity of fibers mediating laser evoked first sensations was in the thin fiber range (less than 10 msec), according to a reaction time study. The results suggest that short CO2 laser pulses produce both non-pain and pain sensations, but that both these sensations are based on the activation of the same primary afferent fiber population of slowly conducting nociceptive fibers. Central summation of primary afferent impulses is needed to elicit a liminal non-painful sensation, and an increased number of impulses in the same fibers produces pain.

Adult↗

PubMed1985

Responses of single cutaneous fibers to noxious thermal pulse stimulation of cat upper hind limb.

Previous experiments have shown that cats respond to noxious thermal pulse stimulation of the upper hind limb at an average latency of 2.3 sec. To determine if C fiber afferents could mediate this response, we recorded the response latency and threshold of single fibers of cat femoral cutaneous nerve to the same stimuli used in the behavioral experiments. Of 28 C fibers tested, 10 (36%) responded to heating; 4 (17%) of 24 fibers with conduction velocities of 2.5-30 m/sec responded to heat. All fibers but one discharged within 1.0 sec of thermal pulse onset (median: 800 msec) at an average and median threshold of 46 degrees C. Thermal nociceptors with C fiber afferents could mediate the initiation of behavioral nocifensive responses to heat in the cat.

Afferent Pathways↗