Perceived controllability modulates the neural response to pain

The response to painful stimulation depends not only on peripheral nociceptive input but also on the cognitive and affective context in which pain occurs. One contextual variable that affects the neural and behavioral response to nociceptive stimulation is the degree to which pain is perceived to be controllable. Previous studies indicate that perceived controllability affects pain tolerance, learning and motivation, and the ability to cope with intractable pain, suggesting that it has profound effects on neural pain processing. To date, however, no neuroimaging studies have assessed these effects. We manipulated the subjects' belief that they had control over a nociceptive stimulus, while the stimulus itself was held constant. Using functional magnetic resonance imaging, we found that pain that was perceived to be controllable resulted in attenuated activation in the three neural areas most consistently linked with pain processing: the anterior cingulate, insular, and secondary somatosensory cortices. This suggests that activation at these sites is modulated by cognitive variables, such as perceived controllability, and that pain imaging studies may therefore overestimate the degree to which these responses are stimulus driven and generalizable across cognitive contexts. [References: 28]

Individual differences in the effects of perceived controllability on pain perception: critical role of the prefrontal cortex

The degree to which perceived controllability alters the way a stressor is experienced varies greatly among individuals. We used functional magnetic resonance imaging to examine the neural activation associated with individual differences in the impact of perceived controllability on self-reported pain perception. Subjects with greater activation in response to uncontrollable (UC) rather than controllable (C) pain in the pregenual anterior cingulate cortex (pACC), periaqueductal gray (PAG), and posterior insula/SII reported higher levels of pain during the UC versus C conditions. Conversely, subjects with greater activation in the ventral lateral prefrontal cortex (VLPFC) in anticipation of pain in the UC versus C conditions reported less pain in response to UC versus C pain. Activation in the VLPFC was significantly correlated with the acceptance and denial subscales of the COPE inventory [Carver, C. S., Scheier, M. F., & Weintraub, J. K. Assessing coping strategies: A theoretically based approach. Journal of Personality and Social Psychology, 56, 267–283, 1989], supporting the interpretation that this anticipatory activation was associated with an attempt to cope with the emotional impact of uncontrollable pain. A regression model containing the two prefrontal clusters (VLPFC and pACC) predicted 64% of the variance in pain rating difference, with activation in the two additional regions (PAG and insula/SII) predicting almost no additional variance. In addition to supporting the conclusion that the impact of perceived controllability on pain perception varies highly between individuals, these findings suggest that these effects are primarily top-down, driven by processes in regions of the prefrontal cortex previously associated with cognitive modulation of pain and emotion regulation.

Individual Differences in Amygdala and Ventromedial Prefrontal Cortex Activity are Associated with Evaluation Speed and Psychological Well-being

Using functional magnetic resonance imaging, we examined whether individual differences in amygdala activation in response to negative relative to neutral information are related to differences in the speed with which such information is evaluated, the extent to which such differences are associated with medial prefrontal cortex function, and their relationship with measures of trait anxiety and psychological well-being (PWB). Results indicated that faster judgments of negative relative to neutral information were associated with increased left and right amygdala activation. In the prefrontal cortex, faster judgment time was associated with relative decreased activation in a cluster in the ventral anterior cingulate cortex (ACC, BA 24). Furthermore, people who were slower to evaluate negative versus neutral information reported higher PWB. Importantly, higher PWB was strongly associated with increased activation in the ventral ACC for negative relative to neutral information. Individual differences in trait anxiety did not predict variation in judgment time or in amygdala or ventral ACC activity. These findings suggest that people high in PWB effectively recruit the ventral ACC when confronted with potentially aversive stimuli, manifest reduced activity in subcortical regions such as the amygdala, and appraise such information as less salient as reflected in slower evaluative speed.

A simple two-stage design for quantitative responses with application to a study in diabetic neuropathic pain

Two-stage designs offer substantial advantages for early phase II studies. The interim analysis following the first stage allows the study to he stopped for futility, or more positively, it might lead to early progression to the trials needed for late phase H and phase III. If the study is to continue to its second stage, then there is an opportunity for a revision of the total sample size. Two-stage designs have been implemented widely in oncology studies in which there is a single treatment arm and patient responses are binary. In this paper the case of two-arm comparative studies in which responses are quantitative is considered. This setting is common in therapeutic areas other than oncology. It will be assumed that observations are normally distributed, but that there is some doubt concerning their standard deviation, motivating the need for sample size review. The work reported has been motivated by a study in diabetic neuropathic pain, and the development of the design for that trial is described in detail. Copyright (C) 2008 John Wiley & Sons, Ltd.

The Ca(v)2.3 calcium channel antagonist SNX-482 reduces dorsal horn neuronal responses in a rat model of chronic neuropathic pain

Neuropathic pain is a difficult state to treat, characterized by alterations in sensory processing that can include allodynia (touch-evoked pain). Evidence exists for nerve damage-induced plasticity in both transmission and modulatory systems, including changes in voltage-dependent calcium channel (VDCC) expression and function; however, the role of Ca(v)2.3 calcium channels has not clearly been defined. Here, the effects of SNX-482, a selective Ca(v)2.3 antagonist, on sensory transmission at the spinal cord level have been investigated in the rat. The spinal nerve ligation (SNL) model of chronic neuropathic pain [Kim & Chung, (1992) Pain, 50, 355-363] was used to induce mechanical allodynia, as tested on the ipsilateral hindpaw. In vivo electrophysiological measurements of dorsal horn neuronal responses to innocuous and noxious electrical and natural stimuli were made after SNL and compared to sham-operated animals. Spinal SNX-482 (0.5-4 mu g/50 mu L) exerted dose-related inhibitions of noxious C-fibre- and A delta-fibre-mediated neuronal responses in conditions of neuropathy, but not in sham-operated animals. Measures of spinal cord hyperexcitability and nociception were most susceptible to SNX-482. In contrast, non-noxious A beta-mediated responses were not affected by SNX-482. Moreover, responses to innocuous mechanical and also thermal stimuli were more sensitive to SNX-482 in SNL than control animals. This study is the first to demonstrate an antinociceptive role for SNX-482-sensitive channels in dorsal horn neurons during neuropathy. These data are consistent with plasticity in Ca(V)2.3 calcium channel expression and suggest a potential selective target to reduce nociceptive transmission during conditions of nerve damage.

Childhood emotional abuse and neglect as predictors of psychological and physical symptoms in women presenting to a primary care practice

Objective: There were two aims to this study: first to examine whether emotional abuse and neglect are significant predictors of psychological and somatic symptoms, and lifetime trauma exposure in women presenting to a primary care practice, and second to examine the strength of these relationships after controlling for the effects of other types of childhood abuse and trauma. Method: Two-hundred and five women completed the Childhood Trauma Questionnaire (Bernstein et al., 1994), Trauma History Questionnaire (Green, 1996), the Symptom Checklist-revised (Derogatis, 1997), and the Revised Civilian Mississippi Scale for posttraumatic stress disorder (Norris & Perilla, 1996) when presenting to their primary care physician for a visit. Hierarchical multiple regression analyses were conducted to examine unique contributions of emotional abuse and neglect variables on symptom measures while controlling for childhood sexual and physical abuse and lifetime trauma exposure. Results: A history of emotional abuse and neglect was associated with increased anxiety, depression, posttraumatic stress and physical symptoms, as well as lifetime trauma exposure. Physical and sexual abuse and lifetime trauma were also significant predictors of physical and psychological symptoms. Hierarchical multiple regressions demonstrated that emotional abuse and neglect predicted symptomatology in these women even when controlling for other types of abuse and lifetime trauma exposure. Conclusions: Long-standing behavioral consequences may arise as a result of childhood emotional abuse and neglect, specifically, poorer emotional and physical functioning, and vulnerability to further trauma exposure. (C) 2003 Elsevier Ltd. All rights reserved.

Effect of psychological treatment on attentional bias in eating disorders

Objective: The aims of these studies were (a) to investigate the relationship between attentional bias and eating disorders and (b) examine the impact of psychological treatment on attentional bias. Method: The first study compared performance on a pictorial dot probe of 82 female patients with clinical eating disorders and 44 healthy female controls. The second study compared the performance of 31 patients with eating disorder on the same task before and after receiving 20 weeks of standardized cognitive behavior therapy. Twenty-four patients with eating disorder served as wait-list controls. Results: With the exception of neutral shape stimuli, attentional biases for eating, shape, and weight stimuli were greater in the patient sample than the healthy controls. The second study found that attentional biases significantly reduced after active treatment only. Conclusion: Attentional biases may be an expression of the eating disorder. The question of whether such biases warrant specific intervention requires further investigation. (C) 2008 by Wiley Periodicals, Inc.

Conversations around homework: links to parental mental health, family characteristics and child psychological functioning

Parents are increasingly expected to supplement their children's school-based learning by providing support for children's homework. However, parents' capacities to provide such support may vary and may be limited by the experience of depression. This may have implications for child development. In the course of a prospective, longitudinal study of children of postnatally depressed and healthy mothers, we observed mothers (N = 88) and fathers (N = 78) at home during maths homework interactions with their 8-year-old children. The quality of parental communication was rated and analysed in relation to child functioning. The quality of communication of each of the parents was related to their mental state, social class and IQ. While postnatal depression was not directly related to child development, there was some evidence of the influence of maternal depression occurring in the child's school years. Different aspects of parental communication with the child showed specific associations with different child outcomes, over and above the influence of family characteristics. In particular, child school attainment and IQ were associated with parental strategies to encourage representational thinking and mastery motivation, whereas child behavioural adjustment at school and self-esteem were linked to the degree of parental emotional support and low levels of coercion. Notably, the influence of maternal homework support was more strongly related to child outcome than was paternal support, a pattern reflected in mothers' greater involvement in children's schools and school-related activities. Some parents may need guidance in how to support their children's homework if it is to be of benefit to child functioning.

Controlled trial of the short- and long-term effect of psychological treatment of post-partum depression 2. Impact on the mother-child relationship and child outcome

Background: Postnatal depression is associated with adverse child cognitive and socio-emotional outcome. It is not known whether psychological treatment affects the quality of the mother-child relationship and child outcome. Aims: To evaluate the effect of three psychological treatments on the mother-child relationship and child outcome. Method: Women with post-partum depression (n=193) were assigned randomly to routine primary care, non-directive counselling, cognitive-behavioural therapy or psychodynamic therapy The women and their children, were assessed at 43, [8 and 60 months post-partum. Results: Indications of a positive benefit were limited. All three treatments had a significant benefit on maternal reports of early difficulties in relationships with the infants, counselling gave better infant emotional and behaviour ratings at 18 months and more sensitive early mother-infant interactions. The treatments had no significant impact on maternal management of early infant behaviour problems, security of infant-mother attachment. Infant cognitive development or any child outcome at 5 years. Conclusions: Early intervention was of short-term benefit to the mother-child relationship and infant behaviour problems. More-prolonged intervention may be needed. Health visitors could deliver this.

The psychological, neurochemical and functional neuroanatomical mediators of the effects of positive and negative mood on executive functions

In this review we evaluate the cognitive and neural effects of positive and negative mood on executive function. Mild manipulations of negative mood appear to have little effect on cognitive control processes, whereas positive mood impairs aspects of updating, planning and switching. These cognitive effects may be linked to neurochemistry: with positive mood effects mediated by dopamine while negative mood effects may be mediated by serotonin levels. Current evidence on the effects of mood on regional brain activity during executive functions, indicates that the prefrontal cortex is a recurrent site of integration between mood and cognition. We conclude that there is a disparity between the importance of this topic and awareness of how mood affects, executive functions in the brain. Most behavioural and neuroimaging studies of executive function in normal samples do not explore the potential role of variations in mood, yet the evidence we outline indicates that even mild fluctuations in mood can have a significant influence on neural activation and cognition. (c) 2006 Elsevier Ltd. All rights reserved.

Individual variation in psychological and psychomotor symptoms following smoking cessation: the implications for treatment

Some commonly experienced signs and symptoms occur during abstinence from tobacco, but specific signs and symptoms and their intensity vary greatly from individual to individual. The aim of this study was to re-examine psychological and psychomotor symptoms in smokers in the general population, and to explore the individual variation in these. Quitting smokers (n = 123) reported their experiences pre- and post-cessation, on a questionnaire developed for the study. Analysis of variance and frequency analysis showed significant decreases between pre- and post-cessation on positive experiences (F = 9.81, p < 0.0001) but no significant change on negative experiences, suggesting a loss of pleasure rather than increased negative affect upon quitting. The variance of the pre- to post-cessation difference score suggested wide variation in the reporting of withdrawal symptoms. These results lead us to consider the implications for treatment, using cognitive therapies and moderating the significant emphasis that is at present put on withdrawal.

Controlled trial of the short- and long-term effect of psychological treatment of post-partum depression - 1. Impact on maternal mood!

Background: Psychological interventions for postnatal depression can be beneficial in the short term but their longer-term impact is unknown, Aims To evaluate the long-term effect on maternal mood of three psychological treatments in relation to routine primary care. Method: Women with post-partum depression (n=193)were assigned randomly to one of four conditions: routine primary care, non-directive counselling, cognitive-behavioural therapy or psychodynamic therapy. They were assessed immediately after the treatment phase (at 4.5 months) and at 18 and 60 months post-partum. Results: Compared with the control, ail three treatments had a significant impact at 4.5 months on maternal mood (Edinburgh Postnatal Depression Scale, EPDS). Only psychodynamic therapy produced a rate of reduction in depression (Structured Clinical interview for DSM III-R) significantly superior to that of the control. The benefit of treatment was no longer apparent by 9 months postpartum, treatment did not reduce subsequent episodes of post-partum depression. Conclusions: Psychological intervention for post-partum depression improves maternal mood (EPDS) in the short term. However, this benefit is not superior to spontaneous remission in the long term.