Spatial summation in human thermal pain perception: comparison within and between dermatomes.

Spatial summation of thermal pain has recently been reported when stimulus presentations were restricted within a single dermatome. The present study examined whether the magnitude of spatial summation of human thermal pain perception would vary when stimuli were presented within vs. between adjacent dermatomes. Noxious contact heat stimuli from 43 degrees C to 51 degrees C (5 sec duration) were applied to the forearm using areas of 0.21-2.10 cm2. Subjects rated the intensity and unpleasantness of pain using visual analog scales. For stimuli from 45 degrees C to 51 degrees C, there was a significant increase in ratings with increasing stimulus area for both intensity and unpleasantness. When two thermodes were used simultaneously in adjacent dermatomes, the ratings did not differ significantly from those for the same stimulus area in a single dermatome. We conclude that spatial summation both within and between dermatomes plays a significant role in thermal pain perception across the range from threshold to tolerance.     

Inhibition of rat spinothalamic tract neuronal responses to noxious skin heating by stimulation in midbrain periaqueductal gray or lateral reticular formation

The descending inhibitory effects of electrical midbrain stimulation on identified lumbar spinothalamic tract (STT) neurons were investigated in rats anesthetized with sodium pentobarbital. STT units were identified by their antidromic response to stimulation in the contralateral ventrobasal thalamus or medial lemniscus (mean conduction velocity: 18-20 m/sec). Thirty-two of 43 dorsal horn multireceptive STT units gave reproducible responses to noxious heat stimuli (42-56 degrees C, 10 sec) applied to the ventral hind paw. All STT units' responses were suppressed during stimulation (100 msec trains at 100 Hz, 3/sec, 15-300 microA) in PAG or LRF bilaterally. On- and offset of inhibition was rapid (less than 1 sec). STT unit responses to noxious heat were more effectively suppressed by LRF than PAG stimulation, based on statistically significant differences in mean thresholds for inhibition, slopes of current-inhibition plots, and mean current intensities evoking 50% inhibition. Mapping experiments revealed lowest-threshold (less than 25 microA) sites for inhibition to be in ventral PAG, subjacent tegmentum, and LRF bilaterally. STT unit responses increased with graded increases in stimulus temperature from threshold (mean: 46 degrees C) to 56 degrees C. Slopes of temperature-response functions were significantly reduced with little change in threshold during PAG stimulation, whereas these functions were shifted in a parallel manner toward higher temperatures during LRF stimulation. The serotonin antagonist methysergide reduced or blocked PAG- or LRF-evoked inhibition in 3/5 and 5/12 STT units, respectively. These results indicate that STT units are subject to different inhibitory controls from PAG and LRF.     

Treatment of dural sinus thrombosis using selective catheterization and urokinase

Thrombosis of the cerebral dural venous sinuses, cortical draining veins, and deep cerebral veins is a rare clinical finding. Because of its low incidence and multiple etiologies, the optimum therapy for this condition will only be elucidated by a multicenter, randomized prospective study. At our institution, we favor early and aggressive management of cerebral venous sinus thrombosis with transfemoral, venous intradural infusions of the fibrinolytic agent urokinase. To date, treatment of only 13 patients using this technique has been reported in the English literature. This report adds 12 more such treated patients. Despite the presence of preinfusion infarcts in 5 patients, four of which were hemorrhagic, we incurred no major therapeutic morbidity. Functional sinus patency was achieved in 11 of 12 patients, with our only true failure occurring in an individual with symptoms of at least 2 months' duration. Good to excellent clinical outcome was achieved in 10 of 11 patients (one newborn had inadequate follow-up).     

Time course and effective sites for inhibition from midbrain periaqueductal gray of spinal dorsal horn neuronal responses to cutaneous stimuli in the cat

Summary Inhibition of spinal dorsal horn neuronal responses to noxious (50 °C) skin heating by stimulation of the midbrain periaqueductal gray (PAG) was quantitatively investigated in cats anesthetized with sodium pentobarbital and nitrous oxide. Systematic variation of the interval between onset of PAG stimulation (PAGS) and onset of noxious skin heating revealed that a marked reduction of spinal unit heat-evoked discharges occured immediately upon onset of PAGS, and ceased immediately at offset of PAGS with a post-stimulation excitatory rebound. Stimulation at sites in both ventral and dorsal PAG produced inhibition, the strength of which increased sometimes in a linear manner with increasing strength of PAGS. Thresholds for the generation of descending inhibition were higher in dorsal than ventral PAG. PAGS also inhibited spinal unit responses to non-noxious skin stimulation (brushing of hairs). Descending inhibition from PAG is considered as a possible mechanism for analgesia produced by stimulation of PAG and other brainstem structures.The work was supported by a grant from the Deutsche Forschungsgemeinschaft (Zi 110)     

Oral irritant properties of menthol: sensitizing and desensitizing effects of repeated application and cross-desensitization to nicotine

The irritant properties of menthol and its interactions with nicotine were investigated psychophysically in human subjects. In the first experiment, 0.3% L-menthol was applied successively to one side of the tongue 10 times at a 1-min interval (30-s interstimulus interval, ISI), and subjects rated the intensity of the perceived irritation. The intensity of irritation progressively decreased across trials, consistent with desensitization. To test for cross-desensitization of nicotine-evoked irritation by menthol, nicotine (0.6%) was applied to both sides of the tongue simultaneously, 5 min after the conclusion of menthol application. Using both a two-alternative forced choice (2-AFC) paradigm, and also by obtaining independent ratings of the irritant intensity on each side of the tongue, it was found that nicotine-evoked irritation was significantly weaker on the menthol-pretreated side. To control for a possible confounding effect of cooling, nicotine was applied bilaterally only after the cooling sensation of menthol had subsided. Nicotine-induced irritation was still significantly weaker on the menthol-pretreated side, consistent with cross-desensitization of nicotine-evoked irritation by menthol. In a final experiment, menthol was repeatedly applied to one side of the tongue at a shorter (20 s) interval (5-s ISI), and elicited a rapid increase in irritant sensation over the initial trials, consistent with sensitization, followed in subsequent trials by a progressive reduction in irritation (desensitization). After a 5-min rest period, self-desensitization was confirmed. Repeated application of menthol at the same short ISI was then resumed, and resulted in a significant mean increase in irritant intensity consistent with stimulus-induced recovery (SIR).     

Activation of spinal wide dynamic range neurons by intracutaneous microinjection of nicotine

Nicotine evokes pain in the skin and oral mucosa and excites a subpopulation of cutaneous nociceptors, but little is known about the central transmission of chemogenic pain. We have investigated the responses of lumbar spinal wide dynamic range (WDR)-type dorsal horn neurons to intracutaneous (ic) microinjection of nicotine in pentobarbital-anesthetized rats. Nearly all (97%) units responded to nicotine microinjected ic (1 microl) into the low-threshold region of the hind-paw mechanosensitive receptive field in a concentration-related manner (0.01-10%). Responses to repeated injections of 10% nicotine exhibited tachyphylaxis at 5-, 10-, and 15-min interstimulus intervals. Significant tachyphylaxis was not seen with 1% nicotine. All nicotine-responsive units tested (n = 30) also responded to ic histamine (1 microl, 3%) and did not exhibit tachyphylaxis to repeated histamine. However, there was significant cross-tachyphylaxis of nicotine to histamine. Thus 5 min after ic nicotine, histamine-evoked responses were attenuated significantly compared with the initial histamine-evoked response prior to nicotine, with partial recovery over the ensuing 15 min. Neuronal excitation by ic nicotine was not mediated by histamine H1 receptors because ic injection of the H1 receptor antagonist, cetirizine, had no effect on ic nicotine-evoked responses, whereas it significantly attenuated ic histamine-evoked responses in the same neurons. The lowest-threshold portion of cutaneous receptive fields showed a significant expansion in area at 20 min after ic nicotine 10%, indicative of sensitization. Responses to 1% nicotine were significantly reduced after ic injection of the nicotinic antagonist, mecamylamine (0.1% ic), with no recovery over the ensuing 40-60 min. These data indicate that nicotine ic excites spinal WDR neurons, partly via neuronal nicotinic acetylcholine receptors that are presumably expressed in cutaneous nociceptor terminals. Repeated injections of high concentrations of nicotine led to tachyphylaxis and cross-tachyphylaxis with histamine, possibly relevant to peripheral analgesic effects of nicotine.     

Primary malignant melanoma of the common bile duct

Biliary tract obstruction in a 30-year-old man was found to be caused by a malignant melanoma in the common bile duct. Melanin pigment was demonstrated by immunohistochemistry and electron microscopy. Extensive search for a primary malignant melanoma elsewhere was unsuccessful. No pigmented lesions had been removed previously. There were junctional changes in the mucosa of the common bile duct close to the tumor. The malignant melanoma in the common bile duct therefore is considered to be primary. Only one other case of primary malignant melanoma in the common bile duct has been described in the literature, whereas metastases to the major bile ducts in one autopsy study of malignant melanoma in the more common locations were found with a frequency of 6 per cent.