Östen Hägermark

Traumatic nociceptive pain activates the hypothalamus and the periaqueductal gray: a positron emission tomography study

&NA; The study was conducted to investigate which areas of the brain respond to a painful encounter of minor dermal injury (a model of clinical pain)_elicited by intracutaneous injection of a minute amount of ethanol. Four healthy volunteers (27–46 years) were subjected to positron emission tomographic (PET) investigation of regional cerebral blood flow (rCBF), using [15O]butanol as tracer. The ethanol (20 &mgr;l, 70%) and saline (20 &mgr;l, 0.9%) were injected intracutaneously 3 times in a single‐blinded, semi‐randomised manner for the pain experiment. All the injections were performed, adjacent to each other, at the lateral aspect of the right upper arm. Subjective sensory intensity of pain, unpleasantness and anxiety were rated with separate 100‐mm visual analogue scales together with the Spielbergers State Anxiety Inventory (Spielberger et al. 1970) and heart rate. Paired‐subtraction (pixel‐by‐pixel) between ethanol and saline was performed. Traumatic pain significantly caused higher ratings of intensity and affect scales, i.e., pain intensity, unpleasantness and increased sympathetic activity (evidenced by tachycardia). In contrast the anxiety rating remained unchanged. Acute traumatic nociceptive pain prominently activated the hypothalamus and periaqueductal gray (PAG). In addition, activations of the prefrontal cortex (PFC), insular, anterior cingulate cortex (ACC), posterior parietal cortex (PPC), primary motor/somatosensory areas (MI/SI: face, upper arm), supplementary motor area (SMA), and cerebellum were also demonstrated. The central processing of the pain‐relevant/anticipatory arousal also engaged the PAG. This study demonstrates the involvement of the human cerebral cortex in perception, arousal, cognitive evaluative processes, and, hence, affective reactions (somatic/ autonomic outflow) associated with pain. The pain stimulus of traumatic character may, by its very nature, evoke the central processing to involve both the hypothalamus and the PAG.

The effects of adenosine-5′-triphosphate (ATP) on structure and amine content of rat peritoneal mast cells☆

Abstract The effects of adenosine-5′-triphosphate (ATP) on amine content and cell structure of rat peritoneal mast cells were studied by amine assay as well as by light, fluorescence and electron microscopy. ATP was found to release both histamine and 5-hydroxytryptamine from the cells. Under the experimental conditions employed the amine release was accompanied by the following characteristic morphological changes in the cells: configurational alterations as well as volume increases, contraction of mitochondria, and an intracellular dissolution of granules and cytoplasmic membrane systems. Lastly, ATP was found to exert certain uncommon effects on the nuclear envelope. The morphological findings differ distinctly from those observed in mast cells subjected to various other amine-releasing agents.

Effect in Man of Oral Terbutaline on Cutaneous Reactions Induced by Allergen and Gold Stimulation

In eight atopic subjects wheal and flare responses to intradermally injected horse dander and histamine were determined alter pretreatment with 5 mg oral terbutaline or placebo in a double‐blind cross‐over study. In each individual a dose of allergen was used that produced a flare reaction approximately the size of the ED50 for histamine. Pretreatment with terbutaline was found to attenuate both the wheal and the flare reactions to allergen throughout the observation period of 150 min but only the effect on the wheal response reached Statistical significance (P < 0.01). The responses to histamine were not influenced. In five subjects with cold urticaria, treatment with 2.5 mg terbutaline t.i.d. for a week had no effect on the time period of cold provocation needed to evoke an urticarial lesion.

Effect of Terbutaline, a β2-adrenergic Receptor Stimulating Compound, on Cutaneous Responses to Histamine, Allergen, Compound 48/80, and Trypsin

The β‐adrenoceptor stimulating agent terbutaline (2 ng‐2 μg) injected intradermally in eight atopic subjects produced a dose‐dependent inhibition of the skin reactions induced by subsequently injected allergen. After injection of 0.5 μg terbutaline inhibition of the flare and weal responses was demonstrable throughout the observation period of 90 min.

Cutaneous Responses to Allergen after Local Pretreatment with Beta‐Adrenoceptor Stimulating and Blocking Agents

β‐Adrenoceptor stimulating agents possess anti‐allergic effects in vitro and in vivo. To study the mechanism of action further we compared in 10 atopic subjects the effects on allergen‐induced cutaneous reactions of intradermally (i.d.) injected prenalterol (1–10 μg) terbutaline (2.5‐250 ng) and KWD 2131 (100ng‐2.5 μg), i.e. compounds with preferential actions on β1‐, β2, ‐adrenoceptors and on β‐adrenoceptors not fitting this classification. All injections were given according to a double‐blind design. Terbutaline and KWD 2131 produced a dose‐dependent inhibition of the skin reactions induced by injecting horse dander allergen 5 min later. Terbutaline was about 20 times as potent as KWD 2131 whereas prenalterol was inactive. Propranolol fully blocked the anti‐allergic effect produced by terbutaline.