Rapid-onset opioids and the management of episodic pain

This is the fourth in a short series of articles that focus on what GPs should consider when monitoring and prescribing specialist-initiated palliative-care medicines. Here, the authors summarise the key issues around the use of apid onset opioids in palliative care.

Voluntary facial displays of pain increase suffering in response to nociceptive stimulation

This study demonstrates that making a standardized pain face increases negative affect in response to nociceptive stimulation, even in the absence of social feedback. This suggests that exaggerated facial displays of pain, although often socially reinforced, may also have unintended aversive consequences.

Natural disaster accounting bias and its equivalence across genetic resource stocks

Two sources of bias arise in conventional loss predictions in the wake of natural disasters. One source of bias stems from neglect of accounting for animal genetic resource loss. A second source of bias stems from failure to identify, in addition to the direct effects of such loss, the indirect effects arising from implications impacting animal-human interactions. We argue that, in some contexts, the magnitude of bias imputed by neglecting animal genetic resource stocks is substantial. We show, in addition, and contrary to popular belief, that the biases attributable to losses in distinct genetic resource stocks are very likely to be the same. We derive the formal equivalence across the distinct resource stocks by deriving an envelope result in a model that forms the mainstay of enquiry in subsistence farming and we validate the theory, empirically, in a World-Society-for-the-Protection-of-Animals application

Interpretation bias in preschool children at risk for anxiety: a prospective study

A story-stem paradigm was used to assess interpretation bias in preschool children. Data were available for 131 children. Interpretation bias, behavioural inhibition (BI) and anxiety were assessed when children were aged between 3 years 2 months and 4 years 5 months. Anxiety was subsequently assessed 12-months, 2-years and 5-years later. A significant difference in interpretation bias was found between participants who met criteria for an anxiety diagnosis at baseline, with clinically anxious participants more likely to complete the ambiguous story-stems in a threat-related way. Threat interpretations significantly predicted anxiety symptoms at 12-month follow-up, after controlling for baseline symptoms, but did not predict anxiety symptoms or diagnoses at either 2-year or 5- year follow-up. There was little evidence for a relationship between BI and interpretation bias. Overall, the pattern of results was not consistent with the hypothesis that interpretation bias plays a role in the development of anxiety. Instead, some evidence for a role in the maintenance of anxiety over relatively short periods of time was found. The use of a story-stem methodology to assess interpretation bias in young children is discussed along with the theoretical and clinical implications of the findings.

There’s that scary picture: attention bias to threatening scenes in Williams syndrome

There is increasing evidence that Williams syndrome (WS) is associated with elevated anxiety that is non-social in nature, including generalised anxiety and fears. To date very little research has examined the cognitive processes associated with this anxiety. In the present research, attentional bias for non-social threatening images in WS was examined using a dot-probe paradigm. Participants were 16 individuals with WS aged between 13 and 34 years and two groups of typically developing controls matched to the WS group on chronological age and attentional control ability respectively. The WS group exhibited a significant attention bias towards threatening images. In contrast, no bias was found for group matched on attentional control and a slight bias away from threat was found in the chronological age matched group. The results are contrasted with recent findings suggesting that individuals with WS do not show an attention bias for threatening faces and discussed in relation to neuroimaging research showing elevated amygdala activation in response to threatening non-social scenes in WS.

I see happy people: attention bias towards happy but not angry facial expressions in Williams syndrome

Introduction: Observations of behaviour and research using eye-tracking technology have shown that individuals with Williams syndrome (WS) pay an unusual amount of attention to other people’s faces. The present research examines whether this attention to faces is moderated by the valence of emotional expression. Method: Sixteen participants with WS aged between 13 and 29 years (Mean=19 years 9 months) completed a dot-probe task in which pairs of faces displaying happy, angry and neutral expressions were presented. The performance of the WS group was compared to two groups of typically developing control participants, individually matched to the participants in the WS group on either chronological age or mental age. General mental age was assessed in the WS group using the Woodcock Johnson Test of Cognitive Ability Revised (WJ-COG-R; Woodcock & Johnson, 1989; 1990). Results: Compared to both control groups, the WS group exhibited a greater attention bias for happy faces. In contrast, no between-group differences in bias for angry faces were obtained. Conclusions: The results are discussed in relation to recent neuroimaging findings and the hypersocial behaviour that is characteristic of the WS population.

Attempts to control pain prioritize attention to signals of pain: an experimental study

Clinical evidence suggests that a persistent search for solutions for chronic pain may bring along costs at the cognitive, affective, and behavioral level. Specifically, attempts to control pain may fuel hypervigilance and prioritize attention towards pain-related information. This hypothesis was investigated in an experiment with 41 healthy volunteers. Prioritization of attention towards a signal for pain was measured using an adaptation of a visual search paradigm in which participants had to search for a target presented in a varying number of colored circles. One of these colors (Conditioned Stimulus) became a signal for pain (Unconditioned Stimulus: electrocutaneous stimulus at tolerance level) using a classical conditioning procedure. Intermixed with the visual search task, participants also performed another task. In the pain-control group, participants were informed that correct and fast responses on trials of this second task would result in an avoidance of the Unconditioned Stimulus. In the comparison group, performance on the second task was not instrumental in controlling pain. Results showed that in the pain-control group, attention was more prioritized towards the Conditioned Stimulus than in the comparison group. The theoretical and clinical implications of these results are discussed.

HDAC inhibitors attenuate the development of hypersensitivity in models of neuropathic pain

Histone deacetylase inhibitors (HDACIs) interfere with the epigenetic process of histone acetylation and are known to have analgesic properties in models of chronic inflammatory pain. The aim of this study was to determine whether these compounds could also affect neuropathic pain. Different class I HDACIs were delivered intrathecally into rat spinal cord in models of traumatic nerve injury and antiretroviral drug-induced peripheral neuropathy (stavudine, d4T). Mechanical and thermal hypersensitivity was attenuated by 40% to 50% as a result of HDACI treatment, but only if started before any insult. The drugs globally increased histone acetylation in the spinal cord, but appeared to have no measurable effects in relevant dorsal root ganglia in this treatment paradigm, suggesting that any potential mechanism should be sought in the central nervous system. Microarray analysis of dorsal cord RNA revealed the signature of the specific compound used (MS-275) and suggested that its main effect was mediated through HDAC1. Taken together, these data support a role for histone acetylation in the emergence of neuropathic pain.

Designing a questionnaire to gather carer input to pain assessment for hospitalized people with dementia

We describe development of a questionnaire to elicit pain symptoms and experience, for use by people with dementia or their carers, at hospital admission. The questionnaire provided contextual information to support professionals’ use of the Abbey Pain Scale, a validated tool used by nursing staff internationally. Appropriate information and physical design were required in order, not only to create an approachable questionnaire for patients and carers, but also to ensure fit with hospital processes. Fit with hospital process had significant influence on the final form of the questionnaire, compromising some aspects of design for patients and carers, but this compromise was considered essential to ensure pain management procedures were supplemented by wider, contextual information.

Explicit and implicit subject bias in the ABS journal quality guide

This paper addresses issues raised in two recent papers published in this journal about the UK Association of Business Schools' Journal Quality Guide (ABS Guide). While much of the debate about journal rankings in general, and the ABS Guide in particular, has focused on the construction, power and (mis)use of these rankings, this paper differs in that it explains and provides evidence about explicit and implicit biases in the ABS Guide. In so doing, it poses potentially difficult questions that the editors of the ABS Guide need to address and urgently rectify if the ABS Guide seeks to build and retain legitimacy. In particular, the evidence in this paper shows explicit bias in the ABS Guide against several subject areas, including accounting and finance. It also shows implicit bias against accounting and finance when comparing journal rankings in sub-areas shared between accounting and finance and the broader business management subject areas.

Mind wandering away from pain dynamically engages antinociceptive and default mode brain networks

Human minds often wander away from their immediate sensory environment. It remains unknown whether such mind wandering is unsystematic or whether it lawfully relates to an individual’s tendency to attend to salient stimuli such as pain and their associated brain structure/function. Studies of pain–cognition interactions typically examine explicit manipulation of attention rather than spontaneous mind wandering. Here we sought to better represent natural fluctuations in pain in daily life, so we assessed behavioral and neural aspects of spontaneous disengagement of attention from pain. We found that an individual’s tendency to attend to pain related to the disruptive effect of pain on his or her cognitive task performance. Next, we linked behavioral findings to neural networks with strikingly convergent evidence from functional magnetic resonance imaging during pain coupled with thought probes of mind wandering, dynamic resting state activity fluctuations, and diffusion MRI. We found that (i) pain-induced default mode network (DMN) deactivations were attenuated during mind wandering away from pain; (ii) functional connectivity fluctuations between the DMN and periaqueductal gray (PAG) dynamically tracked spontaneous attention away from pain; and (iii) across individuals, stronger PAG–DMN structural connectivity and more dynamic resting state PAG–DMN functional connectivity were associated with the tendency to mind wander away from pain. These data demonstrate that individual tendencies to mind wander away from pain, in the absence of explicit manipulation, are subserved by functional and structural connectivity within and between default mode and antinociceptive descending modulation networks.

Transient receptor potential ion channels V4 and A1 contribute to pancreatitis pain in mice.

The mechanisms of pancreatic pain, a cardinal symptom of pancreatitis, are unknown. Proinflammatory agents that activate transient receptor potential (TRP) channels in nociceptive neurons can cause neurogenic inflammation and pain. We report a major role for TRPV4, which detects osmotic pressure and arachidonic acid metabolites, and TRPA1, which responds to 4-hydroxynonenal and cyclopentenone prostaglandins, in pancreatic inflammation and pain in mice. Immunoreactive TRPV4 and TRPA1 were detected in pancreatic nerve fibers and in dorsal root ganglia neurons innervating the pancreas, which were identified by retrograde tracing. Agonists of TRPV4 and TRPA1 increased intracellular Ca(2+) concentration ([Ca(2+)](i)) in these neurons in culture, and neurons also responded to the TRPV1 agonist capsaicin and are thus nociceptors. Intraductal injection of TRPV4 and TRPA1 agonists increased c-Fos expression in spinal neurons, indicative of nociceptor activation, and intraductal TRPA1 agonists also caused pancreatic inflammation. The effects of TRPV4 and TRPA1 agonists on [Ca(2+)](i), pain and inflammation were markedly diminished or abolished in trpv4 and trpa1 knockout mice. The secretagogue cerulein induced pancreatitis, c-Fos expression in spinal neurons, and pain behavior in wild-type mice. Deletion of trpv4 or trpa1 suppressed c-Fos expression and pain behavior, and deletion of trpa1 attenuated pancreatitis. Thus TRPV4 and TRPA1 contribute to pancreatic pain, and TRPA1 also mediates pancreatic inflammation. Our results provide new information about the contributions of TRPV4 and TRPA1 to inflammatory pain and suggest that channel antagonists are an effective therapy for pancreatitis, when multiple proinflammatory agents are generated that can activate and sensitize these channels.