Scott M. Fishman

Human brain activation under controlled thermal stimulation and habituation to noxious heat: An fMRI study

Brain activity was studied with functional magnetic resonance imaging (fMRI) following thermal stimulation. Two groups (nu2009=u20096/group) of human male volunteers were given up to four noxious (46°C) and four non‐noxious (41°C) stimuli. In the 46°C experiment, positive signal changes were found in the frontal gyri, anterior and posterior cingulate gyrus, thalamus, motor cortex, somatosensory cortex (SI and SII), supplementary motor area, insula, and cerebellum. Low‐level negative signal changes appeared in the amygdala and hypothalamus. All regions activated by 46°C were also activated by 41°C. However, except for SI and thalamus, significantly more activation was observed for the 46°C stimulus. A significant attenuation of the signal change was observed by the third stimulus for the 46°C, but not for 41°C experiment. Similar findings were replicated in the second group. These fMRI findings specify differences between somatosensory and pain sensation and suggest a number of rich avenues for future research. Magn Reson Med 41:1044–1057, 1999.

Acute plasticity in the human somatosensory cortex following amputation.

WE studied a patient after amputation of an arm and found that in less than 24 h stimuli applied on the ipsilateral face were referred in a precise, topographically organized, modality-specific manner to distinct points on the phantom. Functional magnetic resonance imaging (fMRI) performed one month later showed that brush-evoked activity in the brain demonstrates objective signal changes which correlate with perceptual changes in the phantom hand. This finding in humans corresponds to the observations of immediate plasticity in cortical pathways described in animals, including primates. The results suggest that reorganization of sensory pathways occurs very soon after amputation in humans, potentially due to the unmasking of ordinarily silent inputs rather than sprouting of new axon terminals.

The Opioid Contract in the Management of Chronic Pain

Although the opioid contract is widely used in the administration of chronic opioid therapy, its use has not been well defined and there are few guidelines for developing or revising such tools. We reviewed opioid contracts from 39 major academic pain centers and analyzed every statement for its core meaning. These statements were grouped into general categories and then into specific statement groups. Substantial diversity in the content of the 39 contracts was found. Statements could be grouped into 12 general categories, 43 statements groups, and 125 individual statements. Each of the 39 contracts reviewed contained 22.5% +/- 10.9% of the entire list of 125 statements and 32.6% +/- 11.2% of the 43 statement categories. Contract length averaged less than 3 pages (range: 1 to 1 mean 2.2). We describe frequent and infrequent themes that may be well suited for inclusion in any given contract. While there are many significant issues related to the usage of a formal contract in chronic opioid therapy, there was substantial consistency among the contracts in their universal attempts to improve care through dissemination of information, facilitate a mutually agreed-upon course, or enhance compliance. This study serves as an initial step in considering the risk and benefits of an opioid contract as well as its ideal content and presentation.

Hypercapneic ventilatory response in patients with panic disorder before and after alprazolam treatment and in pre- and postmenstrual women

We tested the ventilatory and anxiety response to hypercapneic (CO2) challenge in women with panic disorder as well as in normal women in the premenstrual phase and mid-points of their menstrual cycles. Panic disorder patients were challenged on two occasions, each time while in the premenstrual phase of the menstrual cycle, receiving an open trial of alprazolam through the intervening 8 weeks between tests. This study confirms previous reports indicating increased sensitivity to CO2 in patients with panic disorder and that this sensitivity can be attenuated by treatment. We found a significant decrease in the ventilatory response of panic disorder patients comparing pre- and post-therapy. We also observed that normal females, while in the premenstrual phase of their menstrual cycle, have a heightened anxiety response to CO2 challenge.

Acute exacerbation of depression after discontinuation of monoamine oxidase inhibitor prior to cardiac surgery

M onoamine oxidase inhibitors (MAOIs) are still widely used for the treatment of depression. Patients are often instructed to discontinue MAOIs two to three weeks prior to anesthesia for elective surgery. This is largely based on several case reports published more than 30 years ago (l-7), that focus on the hemodynamic sequelae associated with these drugs during general anesthesia. We report a case in which tranylcypromine, a MAOI, was discontinued for four weeks prior to elective cardiac surgery (mitral valve reconstruction) and, subsequently, the patient experienced severe symptoms of depression.

Corticosteroid-induced mania after single regional application at the celiac plexus.

WE report the occurrence of symptoms of mania related to corticosteroid injection at the celiac plexus for chronic pancreatitis. Corticosteroids are associated with mental status changes, including mania, confusion, depression, hallucinations, and paranoia. 1 The mechanism for these central nervous system (CNS) perturbations is unknown. The literature suggests that mania is second to psychosis as the most common corticosteroid-related mental status change. Although a relation to dose and daily exposure exists, we found no reports of mania related to a single regional steroid injection. 2,3

Quantitative relationships between plasma beta-endorphin immunoactivity and hemodynamic performance in preoperative cardiac surgical patients

&NA; To quantitate the importance of cardiac dysfunction as a stimulus for plasma immunoactive beta‐endorphin (iBE) secretion, we measured iBE and hemodynamic indices in 65 patients prior to anesthetic induction for coronary artery bypass grafting or valve replacement. Linear regression analysis for the group as a whole showed significant correlations between iBE and stroke index (SI), pulmonary artery wedge pressure (PCW), and right atrial pressure (RAP), but not mean arterial pressure (MAP). Two patient subgroups were identified (P < 0.001 by F‐test): those with low SI and high iBE, or those with high SI and low iBE (cutoffs at 40 ml/m2 and 35 pg/ml, respectively). Correlations between hemodynamics and iBE were always stronger within the low‐SI than the high‐SI subgroups. These correlations were greater for patients with coronary artery than with valvular heart disease. Cardiac output (CO) and cardiac index (CI) correlated with iBE in valve‐replacement and coronary‐grafting groups. These findings were not an artifact of impaired iBE clearance due to renal dysfunction. Our results quantitate the importance of hemodynamic dysfunction for iBE secretion, and indicate that this relationship is particularly strong when stroke index declines below 40 ml/m2.

Naloxone blocks exercise-stimulated water intake in the rat

To examine whether opiate receptors modulate exercise-induced water intake, we measured water intake during four consecutive hours after a one-hour swim stress in male, Sprague-Dawley rats. Increased cumulative water intake was found four hours following exercise and this response was naloxone-reversible (P = 0.06). Suppression of water intake in the naloxone-treated, exercised group was most marked in the first two hours after exercise (P less than 0.05). Non-exercised rats consumed water at a constant, linear rate (P less than 0.05) whether treated with naloxone or saline. These results indicate an endogenous opioid role in regulating exercise-induced water intake in the rat, but do not delineate whether this role reflects a non-specific stress behavior or specific physiological processes related to thirst.

Basic Mechanisms of Pain

It has been well established that pain reflects complex, linked neuroendocrine responses that go far beyond a sensory alarm system. Accordingly, there may be significant medical consequences of inadequate recognition or treatment of pain.