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Kenneth L Casey

Publications and source records attributed to Kenneth L Casey.

17 recordsLinked to original sources
PubMed2006

Placebo effects in laser-evoked pain potentials.

Placebo treatment may affect multiple components of pain, including inhibition of nociceptive input, automatic or deliberative appraisal of pain, or cognitive judgments involved in pain reporting. If placebo analgesia is due in part to an attenuation of early nociceptive processing, then pain-evoked event-related potentials (ERPs) should be reduced with placebo. In this study, we tested for placebo effects in P2 laser-evoked potentials at midline scalp electrodes. We found that placebo treatment produced significant decreases in P2 amplitude, and that P2 placebo responses were large enough to reflect a meaningful difference in nociceptive processing. However, we also found evidence that the very robust placebo-induced decreases in reported pain are not solely explained by early reductions in P2. N2 amplitude was affected by neither placebo nor reduction of laser intensity. These results suggest that placebo treatment affects early nociceptive processing, but that another component of placebo effects in reported pain occurs later, either in evaluation of pain or cognitive judgments about pain reports.

Adult↗
PubMed2006

Placebo-induced changes in spinal cord pain processing.

Pain is an essential sensory modality, signaling injury or threat of injury. Pain perception depends on both biological and psychological factors. However, it is not known whether psychological factors modify spinal mechanisms or if its effect is limited to cortical processing. Here, we use a placebo analgesic model to show that psychological factors affect human spinal nociceptive processes. Mechanical hyperalgesia (hypersensitivity) after an injury is attributable to sensitized sensory neurons in the spinal cord. After a 5 min, 46 degrees C heating of the skin, subjects developed areas of mechanical hyperalgesia. This area was smaller in a placebo condition compared with a baseline condition. This result suggests that placebo analgesia affects the spinal cord as well as supra-spinal pain mechanisms in humans and provides strong supporting evidence that placebo analgesia is not simply altered reporting behavior. Central sensitization is thought to mediate the exaggerated pain after innocuous sensory stimulation in several clinical pain conditions that follow trauma and nervous-system injury. These new data indicate that expectation about pain and analgesia is an important component of the cognitive control of central sensitization.

Adult↗
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↗
PubMed2005

Thermoreceptive innervation of human glabrous and hairy skin: a contact heat evoked potential analysis.

The human palm has a lower heat detection threshold and a higher heat pain threshold than hairy skin. Neurophysiological studies of monkeys suggest that glabrous skin has fewer low threshold heat nociceptors (AMH type 2) than hairy skin. Accordingly, we used a temperature-controlled contact heat evoked potential (CHEP) stimulator to excite selectively heat receptors with C fibers or Adelta-innervated AMH type 2 receptors in humans. On the dorsal hand, 51 degrees C stimulation produced painful pinprick sensations and 41 degrees C stimuli evoked warmth. On the glabrous thenar, 41 degrees C stimulation produced mild warmth and 51 degrees C evoked strong but painless heat sensations. We used CHEP responses to estimate the conduction velocities (CV) of peripheral fibers mediating these sensations. On hairy skin, 41 degrees C stimuli evoked an ultra-late potential (mean, SD; N wave latency: 455 (118) ms) mediated by C fibers (CV by regression analysis: 1.28 m/s, N=15) whereas 51 degrees C stimuli evoked a late potential (N latency: 267 (33) ms) mediated by Adelta afferents (CV by within-subject analysis: 12.9 m/s, N=6). In contrast, thenar responses to 41 and 51 degrees C were mediated by C fibers (average N wave latencies 485 (100) and 433 (73) ms, respectively; CVs 0.95-1.35 m/s by regression analysis, N=15; average CV=1.7 (0.41) m/s calculated from distal glabrous and proximal hairy skin stimulation, N=6). The exploratory range of the human and monkey palm is enhanced by the abundance of low threshold, C-innervated heat receptors and the paucity of low threshold AMH type 2 heat nociceptors.

Adolescent↗
PubMed2004

Placebo-induced changes in FMRI in the anticipation and experience of pain.

The experience of pain arises from both physiological and psychological factors, including one's beliefs and expectations. Thus, placebo treatments that have no intrinsic pharmacological effects may produce analgesia by altering expectations. However, controversy exists regarding whether placebos alter sensory pain transmission, pain affect, or simply produce compliance with the suggestions of investigators. In two functional magnetic resonance imaging (fMRI) experiments, we found that placebo analgesia was related to decreased brain activity in pain-sensitive brain regions, including the thalamus, insula, and anterior cingulate cortex, and was associated with increased activity during anticipation of pain in the prefrontal cortex, providing evidence that placebos alter the experience of pain.

Analgesia↗
PubMed2003

Insights into the pathophysiology of neuropathic pain through functional brain imaging.

We present here an example case of neuropathic pain with heat allodynia as a major symptom to illustrate how the functional imaging of pain may provide new insights into the pathophysiology of painful sensory disorders. Tissue injury of almost any kind, but especially peripheral or central neural tissue injury, can lead to long-lasting spinal and supraspinal re-organization that includes the forebrain. These forebrain changes may be adaptive and facilitate functional recovery, or they may be maladaptive, preventing or prolonging the painful condition, and interfering with treatment. In an experimental model of heat allodynia, we used functional brain imaging to show that: (1) the forebrain activity during heat allodynia is different from that during normal heat pain, and (2) during heat allodynia, specific cortical areas, specifically the dorsolateral prefrontal cortex, can attenuate specific components of the pain experience, such as affect, by reducing the functional connectivity of subcortical pathways. The forebrain of patients with chronic neuropathic pain may undergo pathologically induced changes that can impair the clinical response to all forms of treatment. Functional imaging, including PET, fMRI, and neurophysiological techniques, should help identify brain mechanisms that are critical targets for more effective and more specific treatments for chronic, neuropathic pain.

Adult↗
PubMed2003

Perception of noxious and innocuous heat stimulation among healthy women and women with fibromyalgia: association with mood, somatic focus, and catastrophizing.

Recent studies have demonstrated that persons with fibromyalgia display abnormal processing of different types of painful stimulation, suggesting the disorder is characterized by a central pain-processing deficit not limited specifically to muscle pain. In the present study, 20 women with fibromyalgia and 20 normal, healthy women were compared on measures of pressure pain stimulation and response to contact thermal heat at both noxious and innocuous intensities. Women with fibromyalgia displayed significantly lower pressure pain thresholds at 18 tender point locations as defined by the American College of Rheumatology criteria, as well as lower pressure pain thresholds at five control sites. Women with fibromyalgia had significantly lower heat pain thresholds and tolerances when stimulated on the volar surface of the left forearm. When examining visual analog ratings of intensity and unpleasantness to constant stimuli, a multivariate analysis of variance performed on these ratings indicated that there were significant main effects of level of stimulation and group. Individual analysis of variances at each temperature revealed significant differences between the groups in pain intensity and unpleasantness ratings at both noxious and innocuous temperatures. Multiple regression analyses indicated that greater pain catastrophizing and diagnosis of fibromyalgia were associated with decreased pain thresholds and tolerances in the entire sample, whereas, self-report of depressive symptoms was associated with increased thresholds and tolerances. Self-report of somatic symptoms was not associated with these measures. These findings indicate that persons with fibromyalgia display altered perception of both pressure and thermal stimulation, even at innocuous levels. They also suggest that catastrophic thoughts about pain may play a role in increased pain perception in this population.

Adult↗
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↗
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↗