Odor Sensitivity After Intranasal Insulin Application Is Modulated by Gender

Obesity constitutes a global health care problem, and often eating habits are to blame. For intervention, a thorough understanding of energy intake and expenditure is needed. In recent years, the pivotal role of insulin in connection to energy intake was established. Olfactory sensitivity may be a target of cerebral insulin action to maintain body weight. With this experiment, we aimed to explore the influence of intranasal insulin on olfactory sensitivity for the odors n-butanol and peanut in a placebo-controlled, double-blind setting in a within-subject design. All subjects participated in two experimental sessions on separate days and received either intranasal insulin or placebo in a pseudorandomized order. Application was followed by two olfactory threshold tests for n-butanol and peanut in a pseudorandomized order. After a single dose of intranasal insulin (40 IU) or placebo (0.4 ml), olfactory sensitivity for the odorants n-butanol and peanut were examined in 30 healthy normosmic participants (14 females). Measured blood parameters revealed no decrease in plasma glucose, however, insulin, leptin and cortisol levels were affected following intranasal application. Females' but not males' olfactory sensitivity for n-butanol was lower after intranasal insulin administration vs. placebo. In contrast, olfactory sensitivity for peanut was not influenced by intranasal insulin application. Our results indicate that the effects of cortical insulin levels on processing of specific odors is likely modulated by gender, as central increase of insulin concentration led to a reduced olfactory sensitivity for n-butanol in women only, which might be due to differentially regulated insulin and leptin signaling in men and women

¿Afecta el dolor al volumen local del cerebro? Aportaciones desde un modelo clínico de dolor agudo

Background/Objective:To study pain-brain morphometry associations as a function of post-surgery stages (anesthesia, pain and analgesia) in an acute pain model. Method:Impacted mandible third molar were extracted. Before surgery, an anatomical T1 scan was obtained. Regional brain volumen and subcortical nuclei shapes were obtained. Statistical analyses were done using multiple regression, being pain scores the predictors and voxel volumes, subcortical nuclei volumes and subcortical nuclei shapes, the outcomes. Results:Pain was significantly larger at pain than at anesthesia and analgesia stages, and was higher during anesthesia than during analgesia. Pain intensity was related to grey matter in several cortical (Insula, Mid Frontal and Temporal Gyruses, Precuneus, Anterior Cingulate), and subcortical nuclei (Hippocampus, Thalamus, Putamen, Amygdala), depending of the post-surgical stage. A larger number of brain areas showed significance at pain that at anesthesia and analgesia stages. Conclusions:The relationships of regional brain volumes and subcortical nuclei shapes with pain scores seemed to be unsteady, as they changed with the patient’s actual pain stage.Antecedentes/Objetivo: Se trata de determinar la asociación entre dolor percibido y morfometría cerebral en tres etapas postquirúrgicas (anestesia, dolor y analgesia), en un modelo de dolor agudo. Método: Se obtuvo una imagen cerebral estructural de alta resolución y posteriormente se extrajeron los terceros molares mandibulares impactados. Se realizó un análisis morfométrico para determinar volumen cerebral y forma de núcleos subcorticales. Se realizaron análisis de regresión múltiple, siendo la intensidad del dolor el predictor, y el volumen y la forma de los núcleos subcorticales, medidos pre-cirugía, las variables dependientes.Resultados:El dolor experimentado fue mayor en la etapa de dolor que en las de anestesia y analgesia, y mayor en anestesia que en analgesia. El dolor se asoció con el volumen de materiagris en áreas corticales (insula, giros frontal medial y temporal, precuneus y cingulado anterior) y subcorticales (hipocampo, tálamo, putamen y amígdala). El número de áreas asociadasal dolor experimentado fue mayor en la etapa de dolor que en las de anestesia y analgesia. Conclusiones: La relación entre volumen cerebral regional y forma de núcleos subcorticales con la intensidad del dolor no es fijo, sino que varía en función de la etapa post-quirúrgica (magnitud del dolor).This investigation was partially supported by Research Groups #CTS-138, #CTS-176 and #CTS-1028. (Junta de Andalucía, Spain)

Differential contributions of peripheral and central mechanisms to pain in a rodent model of osteoarthritis

The mechanisms underlying the transition from acute nociceptive pain to centrally maintained chronic pain are not clear. We have studied the contributions of the peripheral and central nervous systems during the development of osteoarthritis (OA) pain. Male Sprague-Dawley rats received unilateral intra-articular injections of monosodium iodoacetate (MIA 1mg) or saline, and weight bearing (WB) asymmetry and distal allodynia measured. Subgroups of rats received intra-articular injections of, QX-314 (membrane impermeable local anaesthetic)+capsaicin, QX-314, capsaicin or vehicle on days 7, 14 or 28 post-MIA and WB and PWT remeasured. On days 7&14 post-MIA, but not day 28, QX-314+capsaicin signfcantly attenuated changes in WB induced by MIA, illustrating a crucial role for TRPV1 expressing nociceptors in early OA pain. The role of top-down control of spinal excitability was investigated. The mu-opioid receptor agonist DAMGO was microinjected into the rostroventral medulla, to activate endogenous pain modulatory systems, in MIA and control rats and refex excitability measured using electromyography. DAMGO (3ng) had a signifcantly larger inhibitory effect in MIA treated rats than in controls. These data show distinct temporal contribtuions of TRPV1 expressing nociceptors and opioidergic pain control systems at later timepoints

Phantom headache: pain-memory-emotion hypothesis for chronic daily headache?

The neurobiology of chronic pain, including chronic daily headache (CDH) is not completely understood. “Pain memory” hypothesis is one of the mechanisms for phantom limb pain. We reviewed the literature to delineate a relation of “pain memory” for the development of CDH. There is a direct relation of pain to memory. Patients with poor memory have less chance to develop “pain memory”, hence less possibility to develop chronic pain. Progressive memory impairment may lead to decline in headache prevalence. A similar relation of pain is also noted with emotional or psychiatric symptoms. Literature review suggests that there is marked overlap in the neural network of pain to that of memory and emotions. We speculate that pain, memory, and emotions are interrelated in triangular pattern, and each of these three is related to other two in bidirectional pattern, i.e., stimulation of one of these will stimulate other symptoms/networks and vice versa (triangular theory for chronic pain). Longstanding or recurrent noxious stimuli will strengthen this interrelation, and this may be responsible for chronicity of pain. Reduction of both chronic pain and psychological symptoms by cognitive behavioral therapy or psychological interventions further suggests a bidirectional interrelation between pain and emotion. Longitudinal studies are warranted on the prevalence of headache and other painful conditions in patients with progressive memory impairment to delineate the relation of pain to memory. Interrelation of headache to emotional symptoms should also be explored

Tension Type Headache in Adolescence and Childhood: Where Are We Now?

Tension type headache (TTH) is a primary headache disorder considered common in children and adolescents. It remains debatable whether TTH and migraine are separate biological entities. This review summarizes the most recent literature of TTH with regards to children and adolescents. Further studies of TTH are needed to develop a biologically based classification system that may be facilitated through understanding changes in the developing brain during childhood and adolescence

Cerebral cortical thickness in chronic pain due to knee osteoarthritis: the effect of pain duration and pain densitization

Objective This study investigates associations between cortical thickness and pain duration, and central sensitization as markers of pain progression in painful knee osteoarthritis. Methods Whole brain cortical thickness and pressure pain thresholds were assessed in 70 participants; 40 patients with chronic painful knee osteoarthritis (age = 66.1± 8.5 years, 21 females, mean duration of pain = 8.5 years), and 30 healthy controls (age = 62.7± 7.4, 17 females). Results Cortical thickness negatively correlated with pain duration mainly in fronto-temporal areas outside of classical pain processing areas (p<0.05, age-controlled, FDR corrected). Pain sensitivity was unrelated to cortical thickness. Patients showed lower cortical thickness in the right anterior insula (p<0.001, uncorrected) with no changes surviving multiple test correction. Conclusion With increasing number of years of suffering from chronic arthritis pain we found increasing cortical thinning in extended cerebral cortical regions beyond recognised pain-processing areas. While the mechanisms of cortical thinning remain to be elucidated, we show that pain progression indexed by central sensitization does not play a major role

Structural Brain Changes Related to Disease Duration in Patients with Asthma

Dyspnea is the impairing, cardinal symptom patients with asthma repeatedly experience over the course of the disease. However, its accurate perception is also crucial for timely initiation of treatment. Reduced perception of dyspnea is associated with negative treatment outcome, but the underlying brain mechanisms of perceived dyspnea in patients with asthma remain poorly understood. We examined whether increasing disease duration in fourteen patients with mild-to-moderate asthma is related to structural brain changes in the insular cortex and brainstem periaqueductal grey (PAG). In addition, the association between structural brain changes and perceived dyspnea were studied. By using magnetic resonance imaging in combination with voxel-based morphometry, gray matter volumes of the insular cortex and the PAG were analysed and correlated with asthma duration and perceived affective unpleasantness of resistive load induced dyspnea. Whereas no associations were observed for the insular cortex, longer duration of asthma was associated with increased gray matter volume in the PAG. Moreover, increased PAG gray matter volume was related to reduced ratings of dyspnea unpleasantness. Our results demonstrate that increasing disease duration is associated with increased gray matter volume in the brainstem PAG in patients with mild-to-moderate asthma. This structural brain change might contribute to the reduced perception of dyspnea in some patients with asthma and negatively impact the treatment outcome

Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain

Back pain is the #1 cause of years lived with disability worldwide, yet surprisingly little is known regarding the biology underlying this symptom. We conducted a genome-wide association study (GWAS) meta-analysis of ch

Nocebo and pain: an overview of the psychoneurobiological mechanisms

Introduction: Nocebo effects are defined as adverse events related to negative expectations and learning processes that are involved in the modulation of the descending pain pathways. Research over the last couple of decades has illustrated that behavioral, psychoneurobiological, and functional changes occur during nocebo-induced pain processing. Objectives: We aimed to review published human and nonhuman research on algesia and hyperalgesia resulting from negative expectations and nocebo effects. Methods: Herein, we searched and comprehensively reviewed scientific literature providing informative knowledge about the psychoneurobiological bases of the nocebo effect in the field of pain with an emphasis on how pain processes are shaped by both cognitive and noncognitive factors. Results: Negative expectations are formed through verbal suggestions of heightened pain, prior nociceptive and painful experiences, and observation of pain in others. Susceptibility to the nocebo effect can be also influenced by genetic variants, conscious and nonconscious learning processes, personality traits, and psychological factors. Moreover, providers\u2019 behaviors, environmental cues and the appearance of medical devices can induce negative expectations that dramatically influence pain perception and processing in a variety of pain modalities and patient populations. Conclusion: Importantly, we concluded that nocebo studies outline how individual expectations may lead to physiological changes underpinning the central integration and processing of magnified pain signaling. Further research is needed to develop strategies that can identify patients with nocebo-vulnerable pain to optimize the psychosocial and therapeutic context in which the clinical encounter occurs, with the ultimate purpose of improving clinical outcomes