Affective Component Of Pain Research Articles

Dissociation of morphine analgesic effects in the sensory and affective components of formalin-induced spontaneous pain in male and female rats

Sex differences in the analgesic effects of morphine have been previously reported in various models that represent the sensory component of pain. However, pain sensation is a complex process that consists of both sensory and affective components. It is presently unclear whether the analgesic effects of morphine between the sensory and affective components of pain are sexually dimorphic. Moreover, differences in morphine dose-response in the two components of pain have not been examined in male and female rats. Therefore, we examined the analgesic effects of morphine on the sensory and affective components of formalin-induced pain behaviors in male and female rats. To discern the sensory component, rats were pretreated with varying doses of morphine and then intraplantar formalin-induced paw flinches were measured. Morphine reduced the number of formalin-induced paw flinches at a treatment dose of 4.0mg/kg. Morphine analgesia was similar across the sexes in the early (phase 1) and late phase (phase 2) of the formalin test. To examine the affective component, rats were pretreated with varying doses of morphine, and then intraplantar formalin-induced conditioned place aversion (CPA) was examined. Formalin produced CPA, which was blocked by morphine at doses of 1.0mg/kg and higher in male and female rats. Lastly, formalin-induced cFos expression and the effects of systemic morphine were examined in the superficial dorsal horn of the spinal cord. Intraplantar formalin produced robust expression of cFos; however, morphine did not attenuate the cFos expression. These results demonstrate a notable dissociation of the analgesic effects of morphine by detecting a fourfold shift in the minimum effective dose between the sensory and affective components of formalin-induced spontaneous pain, that were similar between male and female rats. The findings further suggest disparate mechanisms involved in systemic morphine-induced analgesia in the two components of formalin-induced pain.

Activation of adenylate cyclase-cyclic AMP-protein kinase A signaling by corticotropin-releasing factor within the dorsolateral bed nucleus of the stria terminalis is involved in pain-induced aversion.

Pain is a complex experience involving sensory and affective components. Although the neuronal mechanisms underlying the sensory component of pain have been extensively studied, those underlying its affective component have yet to be elucidated. Recently, we reported that corticotrophin-releasing factor (CRF)-induced depolarization in type II neurons within the dorsolateral bed nucleus of the stria terminalis (dlBNST) is critical for pain-induced aversive responses in rats. However, the intracellular signaling underlying the excitatory effects of CRF and the contribution of such signaling to the induction of pain-induced aversion remain unclear. In the present study, we addressed these issues by conducting whole-cell patch-clamp recordings in rat brain slices and by undertaking behavioral pharmacological analyses. Intracellular perfusion of protein kinase A (PKA) inhibitor Rp-cyclic adenosine monophosphorothioate (Rp-cAMPS) or KT5720 suppressed the excitatory effects of CRF in type II dlBNST neurons, and bath application of Rp-cAMPS also suppressed it. In addition, bath application of forskolin, an adenylate cyclase (AC) activator, mimicked the effects of CRF, and pretreatment with forskolin diminished the excitatory effects of CRF. Furthermore, a conditioned place aversion (CPA) test showed that co-administration of Rp-cAMPS with CRF into the dlBNST suppressed CRF-induced CPA. Intra-dlBNST injection of Rp-cAMPS also suppressed pain-induced CPA. These results suggest that CRF increases excitability of type II dlBNST neurons through activation of the AC-cAMP-PKA pathway, thereby causing pain-induced aversive responses. The present findings shed light on the neuronal mechanisms underlying the negative affective component of pain and may provide therapeutic targets for treating intractable pain accompanied by psychological factors.

Is the experience of pain in patients with temporomandibular disorder associated with the presence of comorbidity?

The aim of this study was to explore the association between the presence of comorbidities and the pain experience in individual patients with temporomandibular disorder (TMD). This clinical trial comprised 112 patients with TMD pain. For all participants the presence of the following comorbid factors was assessed: pain in the neck; somatization; impaired sleep; and depression. Pain experience was evaluated using the McGill Pain Questionnaire (MPQ). For each subject the TMD-pain experience was assessed for three dimensions - sensory, affective, and evaluative - as specified in the MPQ. The association between comorbid factors and these three dimensions of TMD-pain experience was then evaluated using linear regression models. Univariable regression analyses showed that all comorbid factors, except for one factor, were positively associated with the level of pain, as rated by the sensory description of pain, the affective component of pain, and the evaluative experience of pain. The multivariable regression analyses showed that for all MPQ dimensions, depression showed the strongest associations with pain experience. It was found that in the presence of comorbid disorders, patients with TMD experience elevated levels of TMD pain. This information should be taken into consideration in the diagnostic process, as well as in the choice of treatment.

Validation of the Critical-Care Pain Observation Tool and Vital Signs in Relation to the Sensory and Affective Components of Pain During Mediastinal Tube Removal in Postoperative Cardiac Surgery Intensive Care Unit Adults.

The Critical-Care Pain Observation Tool (CPOT) is a behavioral scale recommended in clinical practice guidelines for the assessment of pain in nonverbal intensive care unit (ICU) adults. Although the CPOT has been validated in various ICU patient groups, its association with the affective component of pain has not yet been explored, and in most studies, turning was the used nociceptive procedure. In this study, we aim to validate the use of the CPOT and vital signs in association with the sensory and affective components of pain during mediastinal tube removal (MTR) in postoperative cardiac surgery ICU adults. A sample of 125 patients participated in this prospective repeated-measures, within-subject study. A total of 6 assessments of the main study variables (CPOT scores and patients' self-reports of pain intensity and unpleasantness) were completed by trained research assistants while patients were in the ICU. Assessments were done before, during, and 15 minutes after the nonnociceptive procedure (ie, noninvasive blood pressure taking [NIBP]) and nociceptive procedure (ie, MTR). Discriminant validation of the scale use was supported as higher CPOT scores were obtained during MTR (mean [SD], 2.74 [1.61]) compared with NIBP (mean [SD], 0.50 [0.747]) (t124 = 14.33, P < .001). Similarly, higher values were recorded for mean arterial pressure and heart and respiratory rates during MTR compared with NIBP (P < .01). During MTR, CPOT scores correlated significantly with self-report of pain intensity (r = 0.419, P < .01) and unpleasantness (r = 0.313, P < .01), supporting criterion and convergent validation. Conversely, vital signs did not correlate with either self-report. Study findings confirmed the validity of the CPOT for the assessment of the sensory and affective components of pain in the postcardiac surgery ICU adults. Vital signs were not specific to pain and should be used only as cues to begin further assessment of pain using validated instruments for this purpose.

Topography of microglial activation in sensory- and affect-related brain regions in chronic pain.

Microglial activation in the spinal cord plays a central role in the development and maintenance of chronic pain after a peripheral nerve injury (PNI). There has not yet been a thorough assessment of microglial activation in brain regions associated with pain and reward. To this end, this study uses a mouse model of neuropathic pain in which the left sciatic nerve of male C57Bl/6J mice is loosely constricted (chronic constriction injury) to assess microglial activation in several brain regions 2 weeks after injury, a time point at which pain hypersensitivity is well established. We found significant microglial activation in brain regions associated with sensory pain transmission and affect, including the thalamus, sensory cortex, and amygdala. Activation was consistently most robust in brain regions contralateral to the side of injury. Brain regions not directly involved in either sensory or affective dimensions of pain, such as the motor cortex, did not display microglial activation. This study confirms that PNI induces microglial activation in regions involved with both sensory and affective components of pain. © 2016 Wiley Periodicals, Inc.

Drug discovery: Designing the ideal opioid.

The development of a drug that mimics the pain-relieving activity of opioid compounds, but has fewer side effects, points to an effective strategy for the discovery of many types of drug. See Article p.185 Morphine and other alkaloids from the opium poppy are μ-opioid receptor agonists that have been used to treat pain for many centuries. These authors used a computational approach to dock over three million small molecules to the μ-opioid receptor. Structure-based optimization of the most promising structures led to the identification of a potent agonist, PZM21, with exceptional subtype selectivity for the μ-opioid receptor. In mice, PZM21 generates substantial analgesia, which is fully ablated in μ-opioid receptor knockout animals. This small molecule seems to reduce the affective component of pain, without detectably altering reflexive behaviours, and has little effect on respiration.

Animal models of chronic pain: Advances and challenges for clinical translation.

Chronic pain is a global problem that has reached epidemic proportions. An estimated 20% of adults suffer from pain, and another 10% are diagnosed with chronic pain each year (Goldberg and McGee, ). Despite the high prevalence of chronic pain (an estimated 1.5 billion people are afflicted worldwide), much remains to be understood about the underlying causes of this condition, and there is an urgent requirement for better pain therapies. The discovery of novel targets and the development of better analgesics rely on an assortment of preclinical animal models; however, there are major challenges to translating discoveries made in animal models to realized pain therapies in humans. This review discusses common animal models used to recapitulate clinical chronic pain conditions (such as neuropathic, inflammatory, and visceral pain) and the methods for assessing the sensory and affective components of pain in animals. We also discuss the advantages and limitations of modeling chronic pain in animals as well as highlighting strategies for improving the predictive validity of preclinical pain studies. © 2016 Wiley Periodicals, Inc.

A review of the current studies on neural circuits and mechanisms underlying the affective component of pain

Background Pain is a complex experience, which consists of not only a sensory discriminative dimension but also an affective/motivational dimension. Although the neural systems responsible for the sensory component of pain have been studied extensively, the mechanism underlying pain affect is still unclear. Objective The aim of this article is to explore the neural circuits and mechanisms of the negative affective component of pain. Content This article reviews research advances in the neuronal mechanisms underlying pain-induced aversion. It focuses on the anterior cingulate cortex,amygdala,bed nucleus of the stria terminalis and other related brain regions involved in the processing of affective component of pain. Trend Persistent pain is frequently associated with psychological and emotional dysfunction, studies of the neural circuits and the molecular mechanisms involved in the affective component of pain may have considerable clinical importance in the treatment of chronic pain. Key words: Affective component of pain; Neural circuits; Anterior cingulate cortex; Amygdala; Bed nucleus of the stria terminalis

Modelling affective pain in mice: Effects of inflammatory hypersensitivity on place escape/avoidance behaviour, anxiety and hedonic state

BackgroundThe place escape/avoidance paradigm (PEAP) has been used to assess the affective component of pain in rats. Using the Complete Freund's Adjuvant (CFA) model of inflammatory pain, the current study aimed at developing a mouse version of PEAP and investigating the relation between PEAP and other behavioural responses, namely anxiety-like behaviour, locomotor activity, and hedonic state. New methodA novel paradigm assessing the affective component of pain in mice was developed by modifying the setup known from rat studies: Animals were forced to stay 2×5min in the light and the dark area of a box while being stimulated with a suprathreshold filament on the untreated or treated paw, respectively. This was followed by a 30-min test with unrestricted movement. Anxiety-like behaviour, locomotor activity, and hedonic state were assessed with the elevated zero maze (EZM), an open field setup, and a saccharin preference test, respectively, and correlated with the PEAP behaviour to examine potentially confounding parameters of the novel paradigm. ResultsIn the PEAP, CFA-treated animals spent more time in the light area. CFA also increased anxiety-like behaviour significantly, whereas locomotor activity was unaffected. A significant, albeit modest, reduction in saccharin preference was observed. PEAP responses showed no significant correlations with any other behavioural measure. Comparison with existing method and conclusionsThe PEAP results suggest that this paradigm might be successfully applied in mice to study affective pain. CFA treatment was associated with increased anxiety-like behaviour and anhedonia; however, this appeared unrelated to the PEAP responses.

Presynaptic GABAB receptors reduce transmission at parabrachial synapses in the lateral central amygdala by inhibiting N-type calcium channels.

The nocioceptive information carried by neurons of the pontine parabrachial nucleus to neurons of the lateral division of the central amydala (CeA-L) is thought to contribute to the affective components of pain and is required for the formation of conditioned-fear memories. Importantly, excitatory transmission between parabrachial axon terminals and CeA-L neurons can be inhibited by a number of presynaptic receptors linked to Gi/o-type G-proteins, including α2-adrenoceptors and GABAB receptors. While the intracellular signalling pathway responsible for α2-adrenoceptor inhibition of synaptic transmission at this synapse is known, the mechanism by which GABAB receptors inhibits transmission has not been determined. The present study demonstrates that activation of presynaptic GABAB receptors reduces excitatory transmission between parabrachial axon terminals and CeA-L neurons by inhibiting N-type calcium channels. While the involvement of Gβγ subunits in mediating the inhibitory effects of GABAB receptors on N-type calcium channels is unclear, this inhibition does not involve Gβγ-independent activation of pp60C-src tyrosine kinase. The results of this study further enhance our understanding of the modulation of the excitatory input from parabrachial axon terminals to CeA-L neurons and indicate that presynaptic GABAB receptors at this synapse could be valuable therapeutic targets for the treatment of fear- and pain-related disorders.

Brain Mapping-Based Model of Δ(9)-Tetrahydrocannabinol Effects on Connectivity in the Pain Matrix.

Cannabinoids receive increasing interest as analgesic treatments. However, the clinical use of Δ(9)-tetrahydrocannabinol (Δ(9)-THC) has progressed with justified caution, which also owes to the incomplete mechanistic understanding of its analgesic effects, in particular its interference with the processing of sensory or affective components of pain. The present placebo-controlled crossover study therefore focused on the effects of 20 mg oral THC on the connectivity between brain areas of the pain matrix following experimental stimulation of trigeminal nocisensors in 15 non-addicted healthy volunteers. A general linear model (GLM) analysis identified reduced activations in the hippocampus and the anterior insula following THC administration. However, assessment of psychophysiological interaction (PPI) revealed that the effects of THC first consisted in a weakening of the interaction between the thalamus and the secondary somatosensory cortex (S2). From there, dynamic causal modeling (DCM) was employed to infer that THC attenuated the connections to the hippocampus and to the anterior insula, suggesting that the reduced activations in these regions are secondary to a reduction of the connectivity from somatosensory regions by THC. These findings may have consequences for the way THC effects are currently interpreted: as cannabinoids are increasingly considered in pain treatment, present results provide relevant information about how THC interferes with the affective component of pain. Specifically, the present experiment suggests that THC does not selectively affect limbic regions, but rather interferes with sensory processing which in turn reduces sensory-limbic connectivity, leading to deactivation of affective regions.

My Brain Reads Pain in Your Face, Before Knowing Your Gender

Humans are expert at recognizing facial features whether they are variable (emotions) or unchangeable (gender). Because of its huge communicative value, pain might be detected faster in faces than unchangeable features. Based on this assumption, we aimed to find a presentation time that enables subliminal discrimination of pain facial expression without permitting gender discrimination. For 80 individuals, we compared the time needed (50, 100, 150, or 200 milliseconds) to discriminate masked static pain faces among anger and neutral faces with the time needed to discriminate male from female faces. Whether these discriminations were associated with conscious reportability was tested with confidence measures on 40 other individuals. The results showed that, at 100 milliseconds, 75% of participants discriminated pain above chance level, whereas only 20% of participants discriminated the gender. Moreover, this pain discrimination appeared to be subliminal. This priority of pain over gender might exist because, even if pain faces are complex stimuli encoding both the sensory and the affective component of pain, they signal a danger. This supports the evolution theory relating to the necessity of quickly reading aversive emotions to ensure survival but might also be at the basis of altruistic behavior such as help and compassion. PerspectiveThis study shows that pain facial expression can be processed subliminally after brief presentation times, which might be helpful for critical emergency situations in clinical settings.

Pain modulation effect of breathing-controlled electrical stimulation (BreEStim) is not likely to be mediated by deep and fast voluntary breathing.

Voluntary breathing-controlled electrical stimulation (BreEStim), a novel non-invasive and non-pharmacological treatment protocol for neuropathic pain management, was reported to selectively reduce the affective component of pain possibly by increasing pain threshold. The underlying mechanisms involved in the analgesic effect of BreEStim were considered to result from combination of multiple internal pain coping mechanisms triggered during BreEStim. Findings from our recent studies have excluded possible roles of acupuncture and aversiveness and habituation of painful electrical stimulation in mediating the analgesia effect of BreEStim. To further investigate the possible role of voluntary breathing during BreEStim, the effectiveness of fast and deep voluntary breathing-only and BreEStim on experimentally induced pain was compared in healthy human subjects. Results showed no change in electrical pain threshold after Breathing-only, but a significant increase in electrical pain threshold after BreEStim. There was no statistically significant change in other thresholds after Breathing-only and BreEStim. The findings suggest that the analgesic effect of BreEStim is not likely attributed to fast and deep voluntary breathing. Possible mechanisms are discussed.

Short-term anesthesia inhibits formalin-induced extracellular signal-regulated kinase (ERK) activation in the rostral anterior cingulate cortex but not in the spinal cord.

BackgroundThe rostral anterior cingulate cortex (rACC) has been implicated in the negative affective response to injury, and importantly, it has been shown that activation of extracellular signal-regulated kinase (ERK) signaling in the rACC contributes to the full expression of the affective component of pain in rodents. In this study, we investigated whether administration of anesthesia at the time of injury could reduce phosphorylated-ERK (PERK) expression in the rACC, which might eliminate the negative affective component of noxious stimulation. Intraplantar hindpaw formalin stimulation, an aversive event in the awake animal, was given with or without general isoflurane anesthesia, and PERK expression was subsequently quantified in the rACC using immunohistochemistry. Furthermore, as numerous studies have demonstrated the importance of spinal ERK signaling in the regulation of nociceptive behaviour, we also examined PERK in the superficial dorsal horn of the spinal cord.FindingsFormalin injection with and without short-term (<10 min) general isoflurane anesthesia induced the same level of PERK expression in spinal cord laminae I–II. However, PERK expression was significantly inhibited across all laminae of the rACC in animals anesthetized during formalin injection. The effect of anesthesia was such that levels of PERK were the same in formalin and sham treated anesthesized animals.ConclusionsThis study is the first to demonstrate that isoflurane anesthesia can inhibit formalin-induced PERK in the rACC and therefore might eliminate the unpleasantness of restraint associated with awake hindpaw injection.

Childhood adversities and laboratory pain perception

Childhood adversity has frequently been related to a wide range of psychosomatic complaints in adulthood. The present study examined the relationship between different forms of childhood adversity and laboratory measures of pain. Heat pain tolerance and perceived heat pain intensity were measured in a community-based sample of 62 women (aged 20–64 years). Participants completed the Childhood Trauma Questionnaire (CTQ), which assesses five forms of childhood adversity: physical abuse, sexual abuse, emotional abuse, physical neglect, and emotional neglect. Somatic symptoms, depressive symptoms, and pain catastrophizing were assessed as potential mediators. Bivariate analyses indicated that emotional abuse but no other forms of childhood adversity were significantly related to decreased heat pain tolerance (r=−0.27; P<0.05). Accordingly, multiple regression analyses revealed that only emotional abuse was a significant predictor of heat pain tolerance (β=−0.62; P=0.034) when entering all CTQ subscales simultaneously. Although emotional abuse was also related to somatic symptoms, depressive symptoms, and pain catastrophizing, none of these variables mediated the relationship between childhood adversity and laboratory pain (P>0.1). No significant associations were found between any forms of childhood adversity and heat pain intensity. Our findings indicate that the severity of emotional childhood abuse is associated with decreased pain tolerance, an affective component of pain, but not with heat pain intensity, which has been described as a sensory component of pain.

Cross-frequency coupling in deep brain structures upon processing the painful sensory inputs

Cross-frequency coupling has been shown to be functionally significant in cortical information processing, potentially serving as a mechanism for integrating functionally relevant regions in the brain. In this study, we evaluate the hypothesis that pain-related gamma oscillatory responses are coupled with low-frequency oscillations in the frontal lobe, amygdala and hippocampus, areas known to have roles in pain processing. We delivered painful laser pulses to random locations on the dorsal hand of five patients with uncontrolled epilepsy requiring depth electrode implantation for seizure monitoring. Two blocks of 40 laser stimulations were delivered to each subject and the pain-intensity was controlled at five in a 0–10 scale by adjusting the energy level of the laser pulses. Local-field-potentials (LFPs) were recorded through bilaterally implanted depth electrode contacts to study the oscillatory responses upon processing the painful laser stimulations. Our results show that painful laser stimulations enhanced low-gamma (LH, 40–70Hz) and high-gamma (HG, 70–110Hz) oscillatory responses in the amygdala and hippocampal regions on the right hemisphere and these gamma responses were significantly coupled with the phases of theta (4–7Hz) and alpha (8–12Hz) rhythms during pain processing. Given the roles of these deep brain structures in emotion, these findings suggest that the oscillatory responses in these regions may play a role in integrating the affective component of pain, which may contribute to our understanding of the mechanisms underlying the affective information processing in humans.

Why Social Pain Can Live on: Different Neural Mechanisms Are Associated with Reliving Social and Physical Pain.

Although social and physical pain recruit overlapping neural activity in regions associated with the affective component of pain, the two pains can diverge in their phenomenology. Most notably, feelings of social pain can be re-experienced or “relived,” even when the painful episode has long passed, whereas feelings of physical pain cannot be easily relived once the painful episode subsides. Here, we observed that reliving social (vs. physical) pain led to greater self-reported re-experienced pain and greater activity in affective pain regions (dorsal anterior cingulate cortex and anterior insula). Moreover, the degree of relived pain correlated positively with affective pain system activity. In contrast, reliving physical (vs. social) pain led to greater activity in the sensory-discriminative pain system (primary and secondary somatosensory cortex and posterior insula), which did not correlate with relived pain. Preferential engagement of these different pain mechanisms may reflect the use of different top-down neurocognitive pathways to elicit the pain. Social pain reliving recruited dorsomedial prefrontal cortex, often associated with mental state processing, which functionally correlated with affective pain system responses. In contrast, physical pain reliving recruited inferior frontal gyrus, known to be involved in body state processing, which functionally correlated with activation in the sensory pain system. These results update the physical-social pain overlap hypothesis: while overlapping mechanisms support live social and physical pain, distinct mechanisms guide internally-generated pain.

Systematic review of the behavioural assessment of pain in cats.

The objectives were to review systematically the range of assessment tools used in cats to detect the behavioural expression of pain and the evidence of their quality; and to examine behavioural metrics (considering both the sensory and affective domains) used to assess pain. A search of PubMed and ScienceDirect, alongside articles known to the authors, from 2000 onwards, for papers in English was performed. This was followed by a manual search of the references within the primary data sources. Only peer-reviewed publications that provided information on the assessment tool used to evaluate the behavioural expression of pain in cats, in conscious animals (not anaesthetised cats), were included. No previous systematic reviews were identified. One hundred papers were included in the final assessment. Studies were primarily related to the assessment of pain in relation to surgical procedures, and no clear distinction was made concerning the onset of acute and chronic pain. Ten broad types of instrument to assess pain were identified, and generally the quality of evidence to support the use of the various instruments was poor. Only one specific instrument (UNESP-Botucatu scale) had published evidence of validity, reliability and sensitivity at the level of a randomised control trial, but with a positive rather than placebo control, and limited to its use in the ovariohysterectomy situation. The metrics used within the tools appeared to focus primarily on the sensory aspect of pain, with no study clearly discriminating between the sensory and affective components of pain. Further studies are required to provide a higher quality of evidence for methods used to assess pain in cats. Furthermore, a consistent definition for acute and chronic pain is needed. Tools need to be validated that can detect pain in a range of conditions and by different evaluators (veterinary surgeons and owners), which consider both the sensory and emotional aspects of pain.

Psychological therapies for sickle cell disease and pain.

Sickle cell disease comprises a group of genetic blood disorders. It occurs when the sickle haemoglobin gene is inherited from both parents. The effects of the condition are: varying degrees of anaemia which, if severe, can reduce mobility; a tendency for small blood capillaries to become blocked causing pain in muscle and bone commonly known as 'crises'; damage to major organs such as the spleen, liver, kidneys, and lungs; and increased vulnerability to severe infections. There are both medical and non-medical complications, and treatment is usually symptomatic and palliative in nature. Psychological interventions for individuals with sickle cell disease might complement current medical treatment, and studies of their efficacy have yielded encouraging results. This is an update of a previously published Cochrane Review. To examine the evidence that psychological interventions improve the ability of people with sickle cell disease to cope with their condition. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and the Internet, handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 17 February 2015. All randomised or quasi-randomised controlled trials comparing psychological interventions with no (psychological) intervention in people with sickle cell disease. Both authors independently extracted data and assessed the risk of bias of the included studies. Twelve studies were identified in the searches and seven of these were eligible for inclusion in the review. Five studies, involving 260 participants, provided data for analysis. One study showed that cognitive behaviour therapy significantly reduced the affective component of pain (feelings about pain), mean difference -0.99 (95% confidence interval -1.62 to -0.36), but not the sensory component (pain intensity), mean difference 0.00 (95% confidence interval -9.39 to 9.39). One study of family psycho-education was not associated with a reduction in depression. Another study evaluating cognitive behavioural therapy had inconclusive results for the assessment of coping strategies, and showed no difference between groups assessed on health service utilisation. In addition, family home-based cognitive behavioural therapy did not show any difference compared to disease education. One study of patient education on health beliefs showed a significant improvement in attitudes towards health workers, mean difference -4.39 (95% CI -6.45 to -2.33) and medication, mean difference -1.74 (95% CI -2.98 to -0.50). Nonetheless, these results may not apply across all ages, severity of sickle cell disease, types of pain (acute or chronic), or setting. Evidence for the efficacy of psychological therapies in sickle cell disease is currently limited. This systematic review has clearly identified the need for well-designed, adequately-powered, multicentre randomised controlled trials assessing the effectiveness of specific interventions in sickle cell disease.

FMRI reveals neural activity overlap between adult and infant pain.

Limited understanding of infant pain has led to its lack of recognition in clinical practice. While the network of brain regions that encode the affective and sensory aspects of adult pain are well described, the brain structures involved in infant nociceptive processing are completely unknown, meaning we cannot infer anything about the nature of the infant pain experience. Using fMRI we identified the network of brain regions that are active following acute noxious stimulation in newborn infants, and compared the activity to that observed in adults. Significant infant brain activity was observed in 18 of the 20 active adult brain regions but not in the infant amygdala or orbitofrontal cortex. Brain regions that encode sensory and affective components of pain are active in infants, suggesting that the infant pain experience closely resembles that seen in adults. This highlights the importance of developing effective pain management strategies in this vulnerable population.