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ABSTRACT: Many patients suffer from chronic pain despite the absence of injury or sufficient biomedical disease to explain their pain. These pains are highly resistant to treatment. Psychological therapies designed to help patients undermine the negative thought and behavioral patterns that maintain pain provide only modest pain relief, leading to suspicion that such pain might be maintained by unconscious processes. An article in this issue of Psychosomatic Medicine provides the first experimental evidence that unconscious negative memories can increase pain unpleasantness. These findings are exciting, but the effect sizes are small, which is consistent with the small effects of psychological therapy. It seems that pain stubbornly resists psychological manipulation, but this work provides some hope that psychological therapy for pain can be improved to provide more effective pain relief.
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Dolor Crónico , Esperanza , Humanos , Dolor Crónico/terapia , Dolor Crónico/psicología , Manejo del Dolor/métodos , Inconsciente en Psicología , Psicoterapia/métodosRESUMEN
BACKGROUND: A noxious stimulus following a more intense stimulus often feels less painful than continuous noxious stimulation. This effect, known as offset analgesia (OA), may be due to descending inhibitory control, to changes in peripheral neural transmission or both. The timing and location of noxious thermal stimulation were manipulated to better understand the peripheral and central contributions to OA. METHODS: In a first experiment, participants (n = 29) provided continuous pain ratings as stimuli were delivered to the palm or dorsum of each hand. Offset trials included 44°C (T1), 45°C (T2) and 44°C (T3) stimulation periods. Baseline trials were identical except the T3 temperature fell to 35°C. Constant trials were 44°C throughout. The duration of T1 and T2 was either 1 s or 6 s, whereas T3 was always 12 s. In a second experiment, participants (n = 43) rated pain levels of noxious stimuli presented to the forearms with varying T1 and T2 durations (3, 6, 10 or 13 s) and a 20 s T3 period. RESULTS: OA effects became stronger with increasing inducing durations. OA, however, was not found on the palm even at longer durations. CONCLUSIONS: The increase in OA with duration suggests that accumulated nociceptive signalling is more important to triggering OA than is a decrease in nociceptors' instantaneous firing rates. The lack of OA on the palm, however, implies a key role for the rapidly adapting Type II AMH fibres that may be absent or not readily activated on the palm. Unravelling the relative central and peripheral contribution to OA requires further investigation. SIGNIFICANCE: Offset analgesia (OA) is a fundamentally temporal phenomenon dependent on dynamic changes in stimulus intensity. Here we demonstrate increased OA with increased stimulus duration. This finding implies the more slowly-responding AMH-I peripheral mechanoreceptors contribute to OA. The more rapidly responding AMH-II peripheral mechanoreceptors, however, may be absent or more difficult to activate in the palm where we did not observe OA. This finding implies that the AMH-II receptors are necessary for OA. Our studies suggest methods to unravel the different peripheral and central contributions to OA.
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Analgesia , Mano , Calor , Humanos , Nociceptores , Dolor , Manejo del Dolor , Dimensión del DolorRESUMEN
Offset analgesia (OA) is the disproportionate decrease in pain experience following a slight decrease in noxious heat stimulus intensity. We tested whether sequential offsets would allow noxious temperatures to be reached with little or no perception of pain. Forty-eight participants continuously rated their pain experience during trials containing trains of heat stimuli delivered by Peltier thermode. Stimuli were adjusted through either stepwise sequential increases of 2°C and decreases of 1°C or direct step increases of 1°C up to a maximum of 46°C. Step durations (1, 2, 3, or 6 s) varied by trial. Pain ratings generally followed presented temperature, regardless of step condition or duration. For 6-s steps, OA was observed after each decrease, but the overall pain trajectory was unchanged. We found no evidence that sequential offsets could allow for little pain perception during noxious temperature presentation.NEW & NOTEWORTHY Offset analgesia is the disproportionate decrease in pain experience following a slight decrease in noxious heat stimulus intensity. We tested whether sequential offsets would allow noxious temperatures to be reached with little or no perception of pain. We found little evidence of such overall analgesia. In contrast, we observed analgesic effects after each offset with long-duration stimuli, even with relatively low-temperature noxious stimuli.
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Analgesia , Nocicepción/fisiología , Sensación Térmica/fisiología , Adulto , Femenino , Humanos , Masculino , Dimensión del Dolor , Adulto JovenRESUMEN
OBJECTIVE: Hypnotic suggestion is an empirically validated form of pain control; however, the underlying mechanism remains unclear. METHODS: Thirteen fibromyalgia patients received suggestions to alter their clinical pain, and 15 healthy controls received suggestions to alter experimental heat pain. Suggestions were delivered before and after hypnotic induction with blood oxygen level-dependent (BOLD) activity measured concurrently. RESULTS: Across groups, suggestion produced substantial changes in pain report (main effect of suggestion, F2, 312 = 585.8; p < .0001), with marginally larger changes after induction (main effect of induction, F1, 312 = 3.6; p = .060). In patients, BOLD response increased with pain report in regions previously associated with pain, including thalamus and anterior cingulate cortex. In controls, BOLD response decreased with pain report. All changes were greater after induction. Region-of-interest analysis revealed largely linear patient responses with increasing pain report. Control responses, however, were higher after suggestion to increase or decrease pain from baseline. CONCLUSIONS: Based on behavioral report alone, the mechanism of suggestion could be interpreted as largely similar regardless of the induction or type of pain experience. The functional magnetic resonance imaging data, however, demonstrated larger changes in brain activity after induction and a radically different pattern of brain activity for clinical pain compared with experimental pain. These findings imply that induction has an important effect on underlying neural activity mediating the effects of suggestion, and the mechanism of suggestion in patients altering clinical pain differs from that in controls altering experimental pain. Patient responses imply that suggestions altered pain experience via corresponding changes in pain-related brain regions, whereas control responses imply suggestion engaged cognitive control.
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Fibromialgia/fisiopatología , Giro del Cíngulo/fisiopatología , Manejo del Dolor/métodos , Percepción del Dolor/fisiología , Dolor/fisiopatología , Sugestión , Tálamo/fisiopatología , Adulto , Femenino , Fibromialgia/psicología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Dolor/psicologíaRESUMEN
BACKGROUND: Approximately 20% of the adult population suffer from chronic pain that is not adequately treated by current therapies, highlighting a great need for improved treatment options. To develop effective analgesics, experimental human and animal models of pain are critical. Topically/intra-dermally applied capsaicin induces hyperalgesia and allodynia to thermal and tactile stimuli that mimics chronic pain and is a useful translation from preclinical research to clinical investigation. Many behavioral and self-report studies of pain have exploited the use of the capsaicin pain model, but objective biomarker correlates of the capsaicin augmented nociceptive response in nonhuman primates remains to be explored. METHODOLOGY: Here we establish an aversive capsaicin-induced fMRI model using non-noxious heat stimuli in Cynomolgus monkeys (n = 8). BOLD fMRI data were collected during thermal challenge (ON:20 s/42°C; OFF:40 s/35°C, 4-cycle) at baseline and 30 min post-capsaicin (0.1 mg, topical, forearm) application. Tail withdrawal behavioral studies were also conducted in the same animals using 42°C or 48°C water bath pre- and post- capsaicin application (0.1 mg, subcutaneous, tail). PRINCIPAL FINDINGS: Group comparisons between pre- and post-capsaicin application revealed significant BOLD signal increases in brain regions associated with the 'pain matrix', including somatosensory, frontal, and cingulate cortices, as well as the cerebellum (paired t-test, p<0.02, n = 8), while no significant change was found after the vehicle application. The tail withdrawal behavioral study demonstrated a significant main effect of temperature and a trend towards capsaicin induced reduction of latency at both temperatures. CONCLUSIONS: These findings provide insights into the specific brain regions involved with aversive, 'pain-like', responses in a nonhuman primate model. Future studies may employ both behavioral and fMRI measures as translational biomarkers to gain deeper understanding of pain processing and evaluate the preclinical efficacy of novel analgesics.
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Capsaicina/efectos adversos , Cerebelo/diagnóstico por imagen , Lóbulo Frontal/diagnóstico por imagen , Giro del Cíngulo/diagnóstico por imagen , Hiperalgesia/diagnóstico por imagen , Dolor/diagnóstico por imagen , Corteza Somatosensorial/diagnóstico por imagen , Animales , Cerebelo/efectos de los fármacos , Cerebelo/fisiopatología , Femenino , Lóbulo Frontal/efectos de los fármacos , Lóbulo Frontal/fisiopatología , Giro del Cíngulo/efectos de los fármacos , Giro del Cíngulo/fisiopatología , Calor , Humanos , Hiperalgesia/inducido químicamente , Hiperalgesia/fisiopatología , Inyecciones Subcutáneas , Macaca fascicularis , Imagen por Resonancia Magnética , Masculino , Dolor/inducido químicamente , Dolor/fisiopatología , Corteza Somatosensorial/efectos de los fármacos , Corteza Somatosensorial/fisiopatología , Cola (estructura animal) , Sensación Térmica/fisiologíaRESUMEN
The rules of soccer dictate that play, once halted, cannot continue if a player is injured. Players may take advantage of this rule by feigning injury to preserve beneficial match positions. Thirty Euro 2008 matches, 90 Premier League matches and 63 World Cup 2010 matches were reviewed for the timing and severity of injuries. The number of injuries was compared between teams that benefited from stopping the game and those that did not benefit. The number of low-level injuries, not resulting in substitution or subsequent problems, was directly compared for Benefit and Non-Benefit teams for each 15-min period following kick off. Statistical significance was assessed using appropriate non-parametric tests. In addition, seven current players and three managers were interviewed and were asked about feigning injury. Teams that benefited from game stoppages suffered significantly more minor injuries in the last 15 min of matches compared with those that did not benefit. Four of the players directly admitted feigning injury. When it is beneficial, soccer players can and do successfully feign injury to stop the game. Consequently it is possible that others might also successfully feign injury, pain or disease when motivated to do so.
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Guilt is thought to maintain social harmony by motivating reparation. This study compared two methodologies commonly used to identify the neural correlates of guilt. The first, imagined guilt, requires participants to read hypothetical scenarios and then imagine themselves as the protagonist. The second, recollected guilt, requires participants to reflect on times they personally experienced guilt. In the fMRI scanner, participants were presented with guilt/neutral memories and guilt/neutral hypothetical scenarios. Contrasts confirmed a priori predictions that guilt memories, relative to guilt scenarios, were associated with significantly greater activity in regions associated with affect [anterior cingulate cortex (ACC), Caudate, Insula, orbital frontal cortex (OFC)] and social cognition [temporal pole (TP), precuneus). Similarly, results indicated that guilt memories, relative to neutral memories, were also associated with greater activity in affective (ACC, amygdala, Insula, OFC) and social cognition (mPFC, TP, precuneus, temporo-parietal junction) regions. There were no significant differences between guilt hypothetical scenarios and neutral hypothetical scenarios in either affective or social cognition regions. The importance of distinguishing between different guilt inductions inside the scanner is discussed. We offer explanations of our results and discuss ideas for future research.
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Mapeo Encefálico/métodos , Corteza Cerebral/fisiología , Culpa , Imaginación/fisiología , Memoria Episódica , Percepción Social , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Adulto JovenRESUMEN
Mirror-sensations, including touch and pain, are often referred to as synesthetic. The term can be challenged, however, because mirror-sensations lack the incongruency and saliency of synesthesia, may involve problems of perspective rather than entangled sensations, and may be easier to generate with suggestion. If mirror-sensations are truly sensations then they might be expected to act like the true sensation and mirror-pain, for example, might inhibit pain at a distance or itch in the same location. These predictions are highly testable.
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Ilusiones/fisiología , Trastornos de la Percepción/fisiopatología , Percepción del Tacto/fisiología , HumanosRESUMEN
Functional imaging has comprehensively demonstrated that pain involves a number of cortical regions that are often collectively referred to as the pain neuromatrix. This neuromatrix is assumed to be necessary to process the sensory, affective, and cognitive components of pain. Patients who report pain in the apparent absence of injury or disease may experience their symptoms because of dysfunction in one or more components of the pain neuromatrix. Two articles in this edition of Psychosomatic Medicine explore that possibility and provide evidence of altered neural connectivity and activation within components of the pain neuromatrix in patients with low back pain and irritable bowel syndrome. Questions remain as to how best to transition from describing the neural correlates of disease to understanding mechanisms and providing treatments.
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Corteza Cerebral/fisiopatología , Neuroimagen Funcional/métodos , Dolor/diagnóstico , Humanos , Dolor/etiologíaRESUMEN
Some chronic pain patients and healthy individuals experience pain when observing injury or others in pain. To further understand shared pain, we investigated perspective taking, bodily ownership and tooth pain sensitivity. First, participants who reported shared pain (responders) and those who did not (non-responders) viewed an avatar on a screen. Intermittently, 0-3 circles appeared. Sometimes the participant's and avatar's perspective were consistent, both directly viewed the same circles, and sometimes inconsistent, both directly viewed different circles. Responders were faster than non-responders to identify the number of circles when adopting a consistent perspective. Second, participants sat with their left hand hidden while viewing a rubber hand. All participants reported an illusory sensation of feeling stroking in the rubber hand and a sense of ownership of the rubber hand during synchronous stroking of the rubber and hidden hand. The responders also reported feeling the stroking and a sense of ownership of the rubber hand during asynchronous stroking. For experiment three, participants with either low, moderate, or high tooth sensitivity observed a series of images depicting someone eating an ice-popsicle. Low sensitivity participants never reported pain. In contrast, moderate and high sensitivity participants reported pain in response to an image depicting someone eating an ice popsicle (4 and 19% of the time, respectively) and depicting someone eating an ice-popsicle and expressing pain (23 and 40%, respectively). In summary, responders have reduced ability to distinguish their own and others' visual perspective and enhanced ability to integrate a foreign arm into their bodily representation. The tendency to share pain is also enhanced when an observed pain is commonly experienced by the observer. Shared pain may therefore involve reactivation of pain memories or pain schema that are readily integrated into a self perspective and bodily representation.
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Analgesia/métodos , Mapeo Encefálico , Encéfalo/fisiología , Dolor/psicología , Efecto Placebo , Femenino , Humanos , MasculinoRESUMEN
The stimulus-evoked response is the principle measure used to elucidate the timing and spatial location of human brain activity. Brain and behavioural responses to pain are influenced by multiple intrinsic and extrinsic factors and display considerable, natural trial-by-trial variability. However, because the neuronal sources of this variability are poorly understood the functional information it contains is under-exploited for understanding the relationship between brain function and behaviour. We recorded simultaneous EEG-fMRI during rest and noxious thermal stimulation to characterise the relationship between natural fluctuations in behavioural pain-ratings, the spatiotemporal dynamics of brain network responses and intrinsic connectivity. We demonstrate that fMRI response variability in the pain network is: dependent upon its resting-state functional connectivity; modulated by behaviour; and correlated with EEG evoked-potential amplitude. The pre-stimulus default-mode network (DMN) fMRI signal predicts the subsequent magnitude of pain ratings, evoked-potentials and pain network BOLD responses. Additionally, the power of the ongoing EEG alpha oscillation, an index of cortical excitability, modulates the DMN fMRI response to pain. The complex interaction between alpha-power, DMN activity and both the behavioural report of pain and the brain's response to pain demonstrates the neurobiological significance of trial-by-trial variability. Furthermore, we show that multiple, interconnected factors contribute to both the brain's response to stimulation and the psychophysiological emergence of the subjective experience of pain.
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Mapeo Encefálico , Encéfalo/fisiopatología , Umbral del Dolor/fisiología , Dolor/fisiopatología , Adulto , Electroencefalografía , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Imagen Multimodal , Adulto JovenRESUMEN
OBJECTIVES: The diagnosis of fibromyalgia is based on self-report and indirect measures and thus is unavoidably influenced by patients' own understanding of their symptoms. In order to provide appropriate support for people with fibromyalgia, it is important to understand variation in patients' interpretations of their own symptoms. METHODS: Twenty people with fibromyalgia participated in email interviews exploring their experiences, history and diagnosis. Respondents answered a series of questions in their own time. Rich accounts were elicited. A hermeneutic phenomenological approach linked two stages of analysis. In the first instance, an in-depth, inductive analysis was developed around a subset of eight transcripts, using interpretative phenomenological analysis. The outcomes of this work were then used to inform a template analysis, which was applied to the remaining 12 transcripts, in order to extend and check the credibility of the in-depth analysis. RESULTS: Participants described enduring the course of a 'giant mess' of unpleasant symptoms, some of which were understood to be symptoms of fibromyalgia and some the interactive or parallel effects of comorbid illness. The respondents also demonstrated their considerable efforts at imposing order and sense on complexity and multiplicity, in terms of the instability of their symptoms. They expressed ambivalence towards diagnosis, doctors and medication, and we noted that each of the above areas appeared to come together to create a context of relational uncertainty, which undermined the security of connections to family, friends, colleagues and the workplace. CONCLUSIONS: Three key issues were discussed. First, there was not one overall symptom (e.g., pain) driving the unpleasantness of fibromyalgia; second, participants spent excessive time and energy trying to manage forces outside their control; third, because there is no definitive 'fibromyalgia experience', each diagnosis is unique, and our participants often appeared to be struggling to understand the course of their illness. Issues of stigma and legitimacy need to be considered carefully by health professionals in the context of the complex and uncertain experience of patients.
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Actitud Frente a la Salud , Autoevaluación Diagnóstica , Fibromialgia/psicología , Adaptación Psicológica , Adolescente , Adulto , Femenino , Fibromialgia/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Investigación Cualitativa , Adulto JovenRESUMEN
The present study compared neural activity in participants with blunted (N = 9) or exaggerated (N = 8) cardiac stress reactions. Neural activity was recorded with fMRI while participants performed a validated stress task and control task. Exaggerated reactors exhibited significant increases in heart rate from control to stress task, whereas blunted reactors had no change in heart rate. Blunted reactors also had reduced activation in the anterior midcingulate cortex and insula compared to exaggerated reactors during the stress condition, and a greater deactivation in the amygdala and posterior cingulate. The biological differences between groups in response to the stress task could not be explained by subjective measures of engagement, stressfulness, or difficulty. This study supports the notion that blunted peripheral physiological stress reactivity may be a marker of a corresponding under-recruitment of brain systems during behavioral states requiring motivated action.
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Encéfalo/fisiología , Gasto Cardíaco/fisiología , Frecuencia Cardíaca/fisiología , Adulto , Presión Sanguínea/fisiología , Mapeo Encefálico , Electrocardiografía , Prueba de Esfuerzo , Humanos , Imagen por Resonancia Magnética , MasculinoRESUMEN
Two experiments examined biases in children's (5/6- and 7/8-year-olds) and adults' moral judgments. Participants at all ages judged that it was worse to produce harm when harm occurred (a) through action rather than inaction (omission bias), (b) when physical contact with the victim was involved (physical contact principle), and (c) when the harm was produced as a direct means to an end rather than as an unintended but foreseeable side effect of the action (intention principle). The youngest participants, however, did not incorporate benefit when making judgments about situations in which harm to one individual resulted in benefit to five individuals. Older participants showed some preference for benefit resulting from action (commission) as opposed to inaction (omission). The findings are discussed in the context of the theory that moral judgments result, in part, from the operation of an inherent, intuitive moral faculty compared with the theory that moral judgments require development of necessary cognitive abilities.
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Víctimas de Crimen/psicología , Inhibición Psicológica , Intención , Desarrollo Moral , Juicio Moral Retrospectivo , Adulto , Factores de Edad , Niño , Preescolar , Toma de Decisiones , Femenino , Humanos , Individualidad , Intuición , Masculino , Medición de Riesgo , Conducta de Reducción del RiesgoRESUMEN
There exists currently a fair degree of introspection in the pain research community about the value of animal research. This review represents a defense of animal research in pain. We discuss the inherent advantage of animal models over human research as well as the crucial complementary roles animal studies play vis-à-vis human imaging and genetic studies. Finally, we discuss recent developments in animal models of pain that should improve the relevance and translatability of findings using laboratory animals. We believe that pain research using animal models is a continuing necessity-to understand fundamental mechanisms, identify new analgesic targets, and inform, guide and follow up human studies-if novel analgesics are to be developed for the treatment of chronic pain.
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Investigación Biomédica/métodos , Modelos Animales de Enfermedad , Manejo del Dolor , Animales , Evaluación Preclínica de Medicamentos/métodos , Humanos , Dolor/diagnóstico , Dolor/genética , Dolor/fisiopatología , Valor Predictivo de las PruebasAsunto(s)
Dolor/fisiopatología , Humanos , Recién Nacido , Recien Nacido Prematuro , Dimensión del DolorRESUMEN
The majority of commentary on foetal pain has looked at the maturation of neural pathways to decide a lower age limit for foetal pain. This approach is sensible because there must be a minimal necessary neural development that makes pain possible. Very broadly, it is generally agreed that the minimal necessary neural pathways for pain are in place by 24 weeks gestation. Arguments remain, however, as to the possibility of foetal pain before or after 24 weeks. Some argue that the foetus can feel pain earlier than 24 weeks because pain can be supported by subcortical structures. Others argue that the foetus cannot feel pain at any stage because it is maintained in a state of sedation in the womb and lacks further neural and conceptual development necessary for pain. Much of this argument rests on the definition of terms such as 'wakefulness' and 'pain'. If a behavioural and neural reaction to a noxious stimulus is considered sufficient for pain, then pain is possible from 24 weeks and probably much earlier. If a conceptual subjectivity is considered necessary for pain, however, then pain is not possible at any gestational age. Regardless of how pain is defined, it is clear that pain for conceptual beings is qualitatively different than pain for non-conceptual beings. It is therefore a mistake to draw an equivalence between foetal pain and pain in the older infant or adult.