Selective nociceptor activation in volunteers by infrared diode laser

<p>Abstract</p> <p>Background</p> <p>Two main classes of peripheral sensory neurons contribute to thermal pain sensitivity: the unmyelinated C fibers and thinly myelinated Aδ fibers. These two fiber types may differentially underlie different clinical pain states and distinctions in the efficacy of analgesic treatments. Methods of differentially testing C and Aδ thermal pain are widely used in animal experimentation, but these methods are not optimal for human volunteer and patient use. Thus, this project aimed to provide psychophysical and electrophysiological evidence that whether different protocols of infrared diode laser stimulation, which allows for direct activation of nociceptive terminals deep in the skin, could differentially activate Aδ or C fiber thermonociceptors in volunteers.</p> <p>Results</p> <p>Short (60 ms), high intensity laser pulses (SP) evoked monomodal "pricking" pain which was not enhanced by topical capsaicin, whereas longer, lower power pulses (LP) evoked monomodal "burning" pain which was enhanced by topical capsaicin. SP also produced cortical evoked EEG potentials consistent with Aδ mediation, the amplitude of which was directly correlated with pain intensity but was not affected by topical capsaicin. LP also produced a distinct evoked potential pattern the amplitude of which was also correlated with pain intensity, which was enhanced by topical capsaicin, and the latency of which could be used to estimate the conduction velocity of the mediating nociceptive fibers.</p> <p>Conclusions</p> <p>Psychophysical and electrophysiological data were consistent with the ability of short high intensity infrared laser pulses to selectively produce Aδ mediated pain and of longer pulses to selectively produce C fiber mediated thermal pain. Thus, the use of these or similar protocols may be useful in developing and testing novel therapeutics based on the differential molecular mechanisms underlying activation of the two fiber types (e.g., TRPV1, TRPV2, etc). In addition, these protocol may be useful in determining the fiber mediation of different clinical pain types which may, in turn be useful in treatment choice.</p

Subliminal versus supraliminal stimuli activate neural responses in anterior cingulate cortex, fusiform gyrus and insula:a meta-analysis of fMRI studies

Background: Non-conscious neural activation may underlie various psychological functions in health and disorder. However, the neural substrates of non-conscious processing have not been entirely elucidated. Examining the differential effects of arousing stimuli that are consciously, versus unconsciously perceived will improve our knowledge of neural circuitry involved in non-conscious perception. Here we conduct preliminary analyses of neural activation in studies that have used both subliminal and supraliminal presentation of the same stimulus. Methods: We use Activation Likelihood Estimation (ALE) to examine functional Magnetic Resonance Imaging (fMRI) studies that uniquely present the same stimuli subliminally and supraliminally to healthy participants during functional magnetic resonance imaging (fMRI). We included a total of 193 foci from 9 studies representing subliminal stimulation and 315 foci from 10 studies representing supraliminal stimulation. Results: The anterior cingulate cortex is significantly activated during both subliminal and supraliminal stimulus presentation. Subliminal stimuli are linked to significantly increased activation in the right fusiform gyrus and right insula. Supraliminal stimuli show significantly increased activation in the left rostral anterior cingulate. Conclusions: Non-conscious processing of arousing stimuli may involve primary visual areas and may also recruit the insula, a brain area involved in eventual interoceptive awareness. The anterior cingulate is perhaps a key brain region for the integration of conscious and non-conscious processing. These preliminary data provide candidate brain regions for further study in to the neural correlates of conscious experience

A transition from unimodal to multimodal activations in four sensory modalities in humans: an electrophysiological study

<p>Abstract</p> <p>Background</p> <p>To investigate the long-latency activities common to all sensory modalities, electroencephalographic responses to auditory (1000 Hz pure tone), tactile (electrical stimulation to the index finger), visual (simple figure of a star), and noxious (intra-epidermal electrical stimulation to the dorsum of the hand) stimuli were recorded from 27 scalp electrodes in 14 healthy volunteers.</p> <p>Results</p> <p>Results of source modeling showed multimodal activations in the anterior part of the cingulate cortex (ACC) and hippocampal region (Hip). The activity in the ACC was biphasic. In all sensory modalities, the first component of ACC activity peaked 30–56 ms later than the peak of the major modality-specific activity, the second component of ACC activity peaked 117–145 ms later than the peak of the first component, and the activity in Hip peaked 43–77 ms later than the second component of ACC activity.</p> <p>Conclusion</p> <p>The temporal sequence of activations through modality-specific and multimodal pathways was similar among all sensory modalities.</p

The Neuronal Correlates of Digits Backward Are Revealed by Voxel-Based Morphometry and Resting-State Functional Connectivity Analyses

Digits backward (DB) is a widely used neuropsychological measure that is believed to be a simple and effective index of the capacity of the verbal working memory. However, its neural correlates remain elusive. The aim of this study is to investigate the neural correlates of DB in 299 healthy young adults by combining voxel-based morphometry (VBM) and resting-state functional connectivity (rsFC) analyses. The VBM analysis showed positive correlations between the DB scores and the gray matter volumes in the right anterior superior temporal gyrus (STG), the right posterior STG, the left inferior frontal gyrus and the left Rolandic operculum, which are four critical areas in the auditory phonological loop of the verbal working memory. Voxel-based correlation analysis was then performed between the positive rsFCs of these four clusters and the DB scores. We found that the DB scores were positively correlated with the rsFCs within the salience network (SN), that is, between the right anterior STG, the dorsal anterior cingulate cortex and the right fronto-insular cortex. We also found that the DB scores were negatively correlated with the rsFC within an anti-correlation network of the SN, between the right posterior STG and the left posterior insula. Our findings suggest that DB performance is related to the structural and functional organizations of the brain areas that are involved in the auditory phonological loop and the SN

Follicle-stimulating hormone bioactivity in idiopathic normogonadotropic oligoasthenozoospermia: double-blind trial with gonadotropin-releasing hormone

OBJECTIVE: To identify, among patients with idiopathic normogonadotropic oligoasthenozoospermia, those with low bioactive follicle-stimulating hormone (FSH), possibly because of inadequate gonadotropin-releasing hormone (GnRH) pulsatility, whose bioactive FSH and sperm could be improved by GnRH treatment. DESIGN: Randomized, double-blind, placebo-controlled trial with intranasal (IN) GnRH, followed by open GnRH treatment. SETTING: Outpatient endocrinology clinic. PATIENTS: Twenty-eight infertile men with idiopathic normogonadotropic oligoasthenozoospermia. INTERVENTIONS: Gonadotropin-releasing hormone or placebo was self-administered IN every 2 hours. MAIN OUTCOME MEASURES: Serum immunoreactive and bioactive FSH and semen analyses. RESULTS: Ten men showed a low basal FSH bioactive/immunoreactive ratio, which increased in 5 of them under GnRH without parallel sperm modification. Sperm improvements were observed in 10 patients with no parallel evolution of FSH bioactive/immunoreactive ratio. Unpredicted by sperm changes, three pregnancies developed on placebo and 5 on GnRH. CONCLUSIONS: Low bioactive FSH was not the cause of idiopathic normogonadotropic oligoasthenozoospermia in our patients and could not predict response to GnRH. Pulsatile GnRH did not improve sperm beyond random fluctuations

Normogonadotropic primary amenorrhea in a growth hormone-deficient woman with ectopic posterior pituitary: gonadotropin pulsatility and follicle-stimulating hormone bioactivity

We studied the gonadotropic function in a 25-year-old woman suffering from congenital GH deficiency, complaining of primary amenorrhea and wishing to become pregnant. She disclosed a hypoplasic anterior pituitary within a small sella turcica and an ectopic posterior pituitary lobe located below the median eminence. Immunoreactive LH and FSH plasma levels were normal, basal and in response to a GnRH iv bolus but estradiol was low. LH pulse frequency was elevated and FSH bioactivity was low in a granulosa cell aromatase bioassay. Pulsatile administration of iv GnRH at a slower, normal pace, failed to induce ovulation or to increase FSH bioactivity, with or without concomitant GH replacement. However treatment with exogenous im gonadotropins, when preceeded by GH replacement, succeeded in inducing mature oocytes and pregnancy. We concluded that the hypogonadism observed in this patient was due to rapid GnRH pulsatility and poor biological activity of endogenous FSH

CV 205-502 treatment of macroprolactinomas

CV 205-502, a benzoquinoline, is a new nonergot dopamine agonist compound which has been shown to be effective in lowering PRL levels in normal volunteers and in hyperprolactinemic women. Seven patients (4 men and 3 women) presenting with hyperprolactinemia due to macroprolactinoma were treated with CV 205-502 given as a single daily dose at bedtime for up to 12 months. Six patients presented with impaired gonadal function and 2 with galactorrhea. All patients but one had previously been treated with bromocriptine and 4 had undergone pituitary surgery (3 with complementary radiotherapy). Six patients responded within a few weeks to CV 205-502 treatment, PRL levels being normalized (4 patients, 0.075 to 0.150 mg/day) or significantly reduced to restore normal gonadal function (2 patients, 0.225 mg/day). The seventh patient, who had previously been resistant to bromocriptine, also failed to respond to CV 205-502 treatment even after high doses (0.450 mg/day). Under CV 205-502 treatment, follow-up with magnetic resonance imaging revealed a reduction in tumor size of up to 52% of the initial volume in the "PRL-responders" whereas an increase in tumor size was observed in the "nonresponding" patient. No biological disturbance appeared during CV 205-502 treatment and the drug tolerance was very good, with mild side-effects being reported by only 2 patients. In conclusion, CV 205-502, given once daily, appears to be a safe and effective alternative to other dopamine agonists in the treatment of macroprolactinoma, by reducing hyperprolactinemia and tumor size. It was, however, of no benefit in the one patient whose macroprolactinoma had been resistant to bromocriptine