Psychological characteristics of Japanese patients with chronic pain assessed by the Rorschach test

Background  

The increasing number of patients with chronic pain in Japan has become a major issue in terms of the patient's quality of life, medical costs, and related social problems. Pain is a multi-dimensional experience with physiological, affective, cognitive, behavioral and social components, and recommended to be managed via a combination of bio-psycho-social aspects. However, a biomedical approach is still the dominant method of pain treatment in Japan. The current study aimed to evaluate comprehensive psychological functions and processes in Japanese chronic pain patients.     

Pain detection and amelioration in animals on the farm: issues and options

Pain in nonhuman animals is a difficult concept to identify and measure. This article briefly describes the consequences of pain in animals on the farm and explains the reasons for the minimal use of analgesics in farmed animals. Pain can have implications for both animal welfare and economics. The reasons for a low use of analgesics in farmed animals include the lack of recognition of animal pain owing to the apparent lack of anthropomorphically identifiable behavioral changes, concern over human food safety, and lack of research efforts to develop safe analgesics for farm use. Treatment cost relative to the benefits expected is another hindering factor. Interventions to minimize pain must begin with developing objective and practical measures for pain identification and measurement at the farm level. A suggested use of a combination of different behavioral and physiological indicators would help to identify pain in animals. To facilitate continued usage of the methodologies on the farm it also is necessary to evaluate the economic implication of the pain alleviation intervention.     

Pain Detection and Amelioration in Animals on the Farm: Issues and Options

Pain in nonhuman animals is a difficult concept to identify and measure. This article briefly describes the consequences of pain in animals on the farm and explains the reasons for the minimal use of analgesics in farmed animals. Pain can have implications for both animal welfare and economics. The reasons for a low use of analgesics in farmed animals include the lack of recognition of animal pain owing to the apparent lack of anthropomorphically identifiable behavioral changes, concern over human food safety, and lack of research efforts to develop safe analgesics for farm use. Treatment cost relative to the benefits expected is another hindering factor. Interventions to minimize pain must begin with developing objective and practical measures for pain identification and measurement at the farm level. A suggested use of a combination of different behavioral and physiological indicators would help to identify pain in animals. To facilitate continued usage of the methodologies on the farm it also is necessary to evaluate the economic implication of the pain alleviation intervention.     

不同量表用于机械通气新生儿急性疼痛评估的价值分析

目的:分析和比较不同量表用于机械通气新生儿急性疼痛评估的价值。方法:使用总结性、回顾性研究方法,研究时间为2017年3月份到2018年7月份,选择在医院NICU接受机械通气诊治的新生儿56例作为研究对象,所有新生儿都给予高频震荡通气治疗,急性疼痛采用新生儿疼痛/激惹与镇静量表、新生儿急性疼痛评估量表进行评估与分析,记录评估效果。结果:新生儿疼痛/激惹与镇静量表的总体Cronbachα系数为0.698分,最高评分为基础行为状态,最低评分为心率增快。新生儿急性疼痛评估量表的内部一致性总体Cronbachα系数为0.822,最高评分为胎龄,最低评分为SaO2。新生儿疼痛/激惹与镇静量表的护理人员一致性组内相关系数(ICC)为0.992,新生儿急性疼痛评估量表的护理人员一致性组内相关系数ICC为0.987。以新生儿疼痛/激惹与镇静量表作为效标,新生儿急性疼痛评估量表的效标关联效度Spearman相关系数为r=0.855,P=0.007。12名护理人员对新生儿急性疼痛评估量表的选择率为66.7%,对新生儿疼痛/激惹与镇静量表的选择率为33.3%。结论:新生儿疼痛/激惹与镇静量表和新生儿急性疼痛评估量表在机械通气新生儿急性疼痛评估中都有很好的信度与一致性,其中新生儿急性疼痛评估量表的可行性和临床实用性更好。     

Peripheral analgesia: Hitting pain where it hurts

Pain is a complex biological phenomenon that encompasses intricate neurophysiological, behavioural, psychosocial and affective components. Protracted or chronic pain alerts an individual to a possible pathological abnormality and is the main reason why patients visit a primary care physician. Despite the pervasiveness of chronic pain in the population, the effectiveness of current pharmacological therapies remains woefully inadequate and prolonged treatment often leads to the development of undesirable side-effects. Since the vast majority of chronic pain originates in a specific tissue or group of tissues, it may be advantageous to target pain control in the periphery and thereby circumvent the known risks associated with non-specific systemic treatments. This review spotlights a number of promising targets for peripheral pain control including the transient receptor potential (TRP) family of neuronal ion channels, the family of proteinase activated receptors (PARs), cannabinoids, and opioids. A critical appraisal of these targets in preclinical models of disease is given and their suitability as future peripheral analgesics is discussed.     

Distinct basolateral amygdala excitatory inputs mediate the somatosensory and aversive-affective components of pain

Pain is a multidimensional perception that includes unpleasant somatosensory and affective experiences; however, the underlying neural circuits that mediate different components of pain remain elusive. Although hyperactivity of basolateral amygdala glutamatergic (BLA^Glu) neurons is required for the somatosensory and emotional processing of pain, the precise excitatory inputs to BLA^Glu neurons and their roles in mediating different aspects of pain are unclear. Here, we identified two discrete glutamatergic neuronal circuits in male mice: a projection from the insular cortex glutamatergic (IC^Glu) to BLA^Glu neurons, which modulates both the somatosensory and affective components of pain, and a projection from the mediodorsal thalamic nucleus (MD^Glu) to BLA^Glu neurons, which modulates only the aversive-affective component of pain. Using whole-cell recording and fiber photometry, we found that neurons within the IC→BLA and MD→BLA pathways were activated in mice upon inflammatory pain induced by injection of complete Freund’s adjuvant (CFA) into their paws. Optical inhibition of the IC^Glu→BLA pathway increased the nociceptive threshold and induced behavioral place preference in CFA mice. In contrast, optical inhibition of the MD^Glu→BLA pathway did not affect the nociceptive threshold but still induced place preference in CFA mice. In normal mice, optical activation of the IC^Glu→BLA pathway decreased the nociceptive threshold and induced place aversion, while optical activation of the MD^Glu→BLA pathway only evoked aversion. Taken together, our results demonstrate that discrete IC^Glu→BLA and MD^Glu→BLA pathways are involved in modulating different components of pain, provide insights into its circuit basis, and better our understanding of pain perception.     

Nest Building as an Indicator of Health and Welfare in Laboratory Mice

The minimization and alleviation of suffering has moral and scientific implications. In order to mitigate this negative experience one must be able to identify when an animal is actually in distress. Pain, illness, or distress cannot be managed if unrecognized. Evaluation of pain or illness typically involves the measurement of physiologic and behavioral indicators which are either invasive or not suitable for large scale assessment. The observation of nesting behavior shows promise as the basis of a species appropriate cage-side assessment tool for recognizing distress in mice. Here we demonstrate the utility of nest building behavior in laboratory mice as an ethologically relevant indicator of welfare. The methods presented can be successfully used to identify thermal stressors, aggressive cages, sickness, and pain. Observation of nest building behavior in mouse colonies provides a refinement to health and well-being assessment on a day to day basis.     

The Brompton mixture: effects on pain in cancer patients.

Terminally ill cancer patients were given the Brompton mixture and a phenothiazine in an attempt to control their pain. The mixture was administered to patients in three hospital environments: a palliative care unit (PCU), general wards and private rooms. Pain was measured in 92 patients with the McGill-Melzack Pain Questionnaire. The Brompton mixture controlled pain in 90% of patients in the PCU and in 75% to 80% of patients in the wards or private rooms. The differences in pain scores between the PCU patients and the other groups were significant. The mixture produced substantial decreases in the three major dimensions of pain: sensory, affective and evaluative. Comparison of these results with data obtained in an outpatient pain clinic showed that the Brompton mixture was strikingly more effective than the traditional methods of managing cancer pain.     

Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

Background  

Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics.     

What Are You Feeling? Using Functional Magnetic Resonance Imaging to Assess the Modulation of Sensory and Affective Responses during Empathy for Pain

Background

Recent neuroscientific evidence suggests that empathy for pain activates similar neural representations as the first-hand experience of pain. However, empathy is not an all-or-none phenomenon but it is strongly malleable by interpersonal, intrapersonal and situational factors. This study investigated how two different top-down mechanisms – attention and cognitive appraisal - affect the perception of pain in others and its neural underpinnings.

Methodology/Principal Findings

We performed one behavioral (N = 23) and two functional magnetic resonance imaging (fMRI) experiments (N = 18). In the first fMRI experiment, participants watched photographs displaying painful needle injections, and were asked to evaluate either the sensory or the affective consequences of these injections. The role of cognitive appraisal was examined in a second fMRI experiment in which participants watched injections that only appeared to be painful as they were performed on an anesthetized hand. Perceiving pain in others activated the affective-motivational and sensory-discriminative aspects of the pain matrix. Activity in the somatosensory areas was specifically enhanced when participants evaluated the sensory consequences of pain. Perceiving non-painful injections into the anesthetized hand also led to signal increase in large parts of the pain matrix, suggesting an automatic affective response to the putatively harmful stimulus. This automatic response was modulated by areas involved in self/other distinction and valence attribution – including the temporo-parietal junction and medial orbitofrontal cortex.

Conclusions/Significance

Our findings elucidate how top-down control mechanisms and automatic bottom-up processes interact to generate and modulate other-oriented responses. They stress the role of cognitive processing in empathy, and shed light on how emotional and bodily awareness enable us to evaluate the sensory and affective states of others.     

The molecular dynamics of pain control

Pain is necessary for survival, but persistent pain can result in anxiety, depression and a reduction in the quality of life. The discriminative and affective qualities of pain are both thought to be regulated in an activity-dependent fashion. Recent studies have identified cells and molecules that regulate pain sensitivity and the parallel pathways that distribute nociceptive information to limbic or sensory areas of the forebrain. Here, we emphasize the cellular and neurobiological consequences of pain, especially those that are involved in the generation and maintenance of chronic pain. These new insights into pain processing will significantly alter our approach to pain control and the development of new analgesics.     

Stem cells for the treatment of musculoskeletal pain

Musculoskeletal-related pain is one of the most disabling health conditions affecting more than one third of the adult population worldwide. Pain from various mechanisms and origins is currently underdiagnosed and undertreated. The complexity of molecular mechanisms correlating pain and the progression of musculoskeletal diseases is not yet fully understood. Molecular biomarkers for objective evaluation and treatment follow-up are needed as a step towards targeted treatment of pain as a symptom or as a disease. Stem cell therapy is already under investigation for the treatment of different types of musculoskeletal-related pain. Mesenchymal stem cell-based therapies are already being tested in various clinical trials that use musculoskeletal system-related pain as the primary or secondary endpoint. Genetically engineered stem cells, as well as induced pluripotent stem cells, offer promising novel perspectives for pain treatment. It is possible that a more focused approach and reassessment of therapeutic goals will contribute to the overall efficacy, as well as to the clinical acceptance of regenerative medicine therapies. This article briefly describes the principal types of musculoskeletal-related pain and reviews the stem cell-based therapies that have been specifically designed for its treatment.     

Gamma oscillations in human primary somatosensory cortex reflect pain perception

Successful behavior requires selection and preferred processing of relevant sensory information. The cortical representation of relevant sensory information has been related to neuronal oscillations in the gamma frequency band. Pain is of invariably high behavioral relevance and, thus, nociceptive stimuli receive preferred processing. Here, by using magnetoencephalography, we show that selective nociceptive stimuli induce gamma oscillations between 60 and 95 Hz in primary somatosensory cortex. Amplitudes of pain-induced gamma oscillations vary with objective stimulus intensity and subjective pain intensity. However, around pain threshold, perceived stimuli yielded stronger gamma oscillations than unperceived stimuli of equal stimulus intensity. These results show that pain induces gamma oscillations in primary somatosensory cortex that are particularly related to the subjective perception of pain. Our findings support the hypothesis that gamma oscillations are related to the internal representation of behaviorally relevant stimuli that should receive preferred processing.     

Noninvasive Transcranial Electrostimulation of the Brain Endophrinergic Structures: Effects on Human Fatigue and Related Psychophysiological Indices

A randomized single-blind passive placebo-controlled study using a set of seven subjective and objective psychophysiological tests that evaluated the background state and changes in 26 psychophysiological indices (including the physical, cognitive, and affective components of fatigue) showed that transcranial electrostimulation (TES) of endorphinergic structures of the human brain facilitates the normalization of most indices. The positive effects of TES were more pronounced in subjects with strong negative shifts of the initial indices, which suggests a homeostatic character of the effects of activation of the brain endorphin-mediated mechanisms. Special attention was paid to the use of an analog scale for rapid evaluation of fatigue whose validity, reliability, and applicability were proved experimentally by the method of correlation matrices.     

Nonpeptidergic circuits feel your pain

Pain consists of both a sensory component and an affective component. In this issue of Neuron, Braz and colleagues genetically targeted the transneuronal tract tracer wheat germ agglutinin (WGA) to nonpeptidergic nociceptive neurons. They found that these neurons give rise to a specialized multisynaptic circuit that links pain signals in the periphery to limbic/affective regions of the brain.     

Dopamine Precursor Depletion Influences Pain Affect Rather than Pain Sensation

Pain is a multidimensional experience, which includes sensory, cognitive, and affective aspects. Converging lines of evidence indicate that dopaminergic neurotransmission plays an important role in human pain perception. However, the precise effects of dopamine on different aspects of pain perception remain to be elucidated. To address this question, we experimentally decreased dopaminergic neurotransmission in 22 healthy human subjects using Acute Phenylalanine and Tyrosine Depletion (APTD). During APTD and a control condition we applied brief painful laser stimuli to the hand, assessed different aspects of pain perception, and recorded electroencephalographic responses. APTD-induced decreases of cerebral dopaminergic activity did not influence sensory aspects of pain perception. In contrast, APTD yielded increases of pain unpleasantness. The increases of unpleasantness ratings positively correlated with effectiveness of APTD. Our finding of an influence of dopaminergic neurotransmission on affective but not sensory aspects of phasic pain suggests that analgesic effects of dopamine might be mediated by indirect effects on pain affect rather than by direct effects on ascending nociceptive signals. These findings contribute to our understanding of the complex relationship between dopamine and pain perception, which may play a role in various clinical pain states.     

Locating the beginnings of pain

This paper examines the question of whether a fetus can feel pain. The question is divided into four sub questions: What is pain? What is the neurology of pain processing? What is the fetus? Are there good reasons for holding that fetuses feel pain? Pain is suggested to be a multi-dimensional phenomenon drawing on emotional and sensory processes – a consequence of a gradual development involving a number of noxious events rather than an automatic consequence of injury or disease. The non-automaticity of pain is emphasised in the discussion of pain neurology that defies explanations based on a specialised neuronal ‘pain-centre’. The development of the fetus is considered with respect to developmental neurobiology, behavioural and neurological responses to stimulation, and hormonal and neurochemical responses to noxious stimulation. While acknowledging that the development of the fetus is complex, especially after 26 weeks gestation, considerable development is still to occur, even after birth. The fetal pain literature is criticised for tending to exaggerate fetal development. Finally, the difficulty of explaining the subjectivity of pain in materialist terms is discussed. Pain is suggested to arise with development of the necessary neurological, cognitive and emotional structures. Pain experience is placed at approximately 12 months of age, though this is within the context of a continuum of awareness rather than a straight ‘on-off’ switch. The major moral implication of this stance is to place the burden of proof for analgesic use onto clinical measures, rather than relying upon the, so far, poorly supported assumption of pain awareness.     

TRP channels as novel players in the pathogenesis and therapy of itch

Itch (pruritus) is a sensory phenomenon characterized by a (usually) negative affective component and the initiation of a special behavioral act, i.e. scratching. Older studies predominantly have interpreted itch as a type of pain. Recent neurophysiological findings, however, have provided compelling evidence that itch (although it indeed has intimate connections to pain) rather needs to be understood as a separate sensory modality. Therefore, a novel pruriceptive system has been proposed, within which itch-inducing peripheral mediators (pruritogens), itch-selective receptors (pruriceptors), sensory afferents and spinal cord neurons, and defined, itch-processing central nervous system regions display complex, layered responses to itch. In this review, we begin with a current overview on the neurophysiology of pruritus, and distinguish it from that of pain. We then focus on the functional characteristics of the large family of transient receptor potential (TRP) channels in skin-coupled sensory mechanisms, including itch and pain. In particular, we argue that - due to their expression patterns, activation mechanisms, regulatory roles, and pharmacological sensitivities - certain thermosensitive TRP channels are key players in pruritus pathogenesis. We close by proposing a novel, TRP-centered concept of pruritus pathogenesis and sketch important future experimental directions towards the therapeutic targeting of TRP channels in the clinical management of itch.     

Using the Threat Probability Task to Assess Anxiety and Fear During Uncertain and Certain Threat

Fear of certain threat and anxiety about uncertain threat are distinct emotions with unique behavioral, cognitive-attentional, and neuroanatomical components. Both anxiety and fear can be studied in the laboratory by measuring the potentiation of the startle reflex. The startle reflex is a defensive reflex that is potentiated when an organism is threatened and the need for defense is high. The startle reflex is assessed via electromyography (EMG) in the orbicularis oculi muscle elicited by brief, intense, bursts of acoustic white noise (i.e., “startle probes”). Startle potentiation is calculated as the increase in startle response magnitude during presentation of sets of visual threat cues that signal delivery of mild electric shock relative to sets of matched cues that signal the absence of shock (no-threat cues). In the Threat Probability Task, fear is measured via startle potentiation to high probability (100% cue-contingent shock; certain) threat cues whereas anxiety is measured via startle potentiation to low probability (20% cue-contingent shock; uncertain) threat cues. Measurement of startle potentiation during the Threat Probability Task provides an objective and easily implemented alternative to assessment of negative affect via self-report or other methods (e.g., neuroimaging) that may be inappropriate or impractical for some researchers. Startle potentiation has been studied rigorously in both animals (e.g., rodents, non-human primates) and humans which facilitates animal-to-human translational research. Startle potentiation during certain and uncertain threat provides an objective measure of negative affective and distinct emotional states (fear, anxiety) to use in research on psychopathology, substance use/abuse and broadly in affective science. As such, it has been used extensively by clinical scientists interested in psychopathology etiology and by affective scientists interested in individual differences in emotion.