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Painful stimuli elicit first-line reflexive defensive reactions and, in many cases, also evoke second-line recuperative behaviors, the latter of which reflects the sensing of tissue damage and the alleviation of suffering. The lateral parabrachial nucleus (lPBN), composed of external- (elPBN), dorsal- (dlPBN), and central/superior-subnuclei (jointly referred to as slPBN), receives sensory inputs from spinal projection neurons and plays important roles in processing affective information from external threats and body integrity disruption. However, the organizational rules of lPBN neurons that provoke diverse behaviors in response to different painful stimuli from cutaneous and deep tissues remain unclear. In this study, we used region-specific neuronal depletion or silencing approaches combined with a battery of behavioral assays to show that slPBN neurons expressing substance P receptor (NK1R) (lPBNNK1R) are crucial for driving pain-associated self-care behaviors evoked by sustained noxious thermal and mechanical stimuli applied to skin or bone/muscle, while elPBN neurons are dispensable for driving such reactions. Notably, lPBNNK1R neurons are specifically required for forming sustained somatic pain-induced negative teaching signals and aversive memory but are not necessary for fear-learning or escape behaviors elicited by external threats. Lastly, both lPBNNK1R and elPBN neurons contribute to chemical irritant-induced nocifensive reactions. Our results reveal the functional organization of parabrachial substrates that drive distinct behavioral outcomes in response to sustained pain versus external danger under physiological conditions. [ABSTRACT FROM AUTHOR]

Pains are unpleasant, universally unpleasant. What seems trivially true has been rejected by various pain scientists because of several phenomena which allegedly show that there can be pain which is not unpleasant. This rejection is partly based on the ambiguity of 'pain unpleasantness' which can be avoided by distinguishing between primary and secondary pain affect. As for the alleged counterexamples to the above, I will argue that experiences of episodic analgesia as well as the 'pain' experiences of some lobotomized and morphine patients should not be construed as cases in which pain and unpleasantness come apart, but rather as cases in which nociceptive activity and pain dissociate. Regarding the notorious case of pain asymbolia, I will demonstrate that the behaviour of patients with this syndrome suggests that they do feel pain, and that their pain sensations are unpleasant, but much less unpleasant than the pains normal people would have if exposed to the same noxious stimuli. Adopting such an account of these phenomena allows us to retain the widely accepted IASP definition of pain, and thus avoids the issue of integrating non-unpleasant pains into a plausible definition of pain. [ABSTRACT FROM AUTHOR]

Depressive symptoms are common among individuals with chronic pain. Previous work suggests that chronic pain patients have difficulty regulating emotional responses, which is a risk factor for the development of major depressive disorder (MDD). Function of the mesocorticolimbic system, a neural network associated with reward processing, contributes to emotion regulation. This network's dysfunction has been described in chronic pain and MDD research and potentially underlies the relationship among emotion dysregulation, chronic pain, and MDD development. Given that mood induction paradigms have been used to measure emotion regulation, the present study examined intrinsic mesocorticolimbic functional connectivity (FC) after induced sad mood in individuals with and without chronic low back pain (cLBP). Thirty-three MDD-free individuals (17 cLBP) underwent resting-state scanning before and after sad memory-evoked mood induction. A Group [cLBP, healthy control (HC)] x Mood (Neutral, Sadness) repeated measures ANCOVA was conducted on seed-based FC data using a mesolimbic a priori region of interest. Interaction effects were identified in the orbital frontal cortex and inferior frontal gyrus [F(2,29) = 21.07, pFDR <.05. hp2 =.5]. Whereas cLBP showed significantly greater FC between these two regions and the mesolimbic seed under neutral mood, FC among these regions increased in HC and decreased in cLBP under sad mood. Exploratory graph theory analyses further describe between-group differences in mesocorticolimbic network properties. Findings support previous literature describing mesocorticolimbic dysfunction in cLBP and demonstrate aberrant function in emotion regulation. Mesocorticolimbic dysfunction during emotion regulation might contribute to the development of certain depressive phenotypes in chronic pain patients. [ABSTRACT FROM AUTHOR]

Painful stimuli elicit first-line reflexive defensive reactions and, in many cases, also evoke second-line recuperative behaviors, the latter of which reflects the sensing of tissue damage and the alleviation of suffering. The lateral parabrachial nucleus (lPBN), composed of external- (elPBN), dorsal- (dlPBN), and central/superior-subnuclei (jointly referred to as slPBN), receives sensory inputs from spinal projection neurons and plays important roles in processing affective information from external threats and body integrity disruption. However, the organizational rules of lPBN neurons that provoke diverse behaviors in response to different painful stimuli from cutaneous and deep tissues remain unclear. In this study, we used region-specific neuronal depletion or silencing approaches combined with a battery of behavioral assays to show that slPBN neurons expressing substance P receptor ( NK1R ) (lPBN NK1R ) are crucial for driving pain-associated self-care behaviors evoked by sustained noxious thermal and mechanical stimuli applied to skin or bone/muscle, while elPBN neurons are dispensable for driving such reactions. Notably, lPBN NK1R neurons are specifically required for forming sustained somatic pain-induced negative teaching signals and aversive memory but are not necessary for fear-learning or escape behaviors elicited by external threats. Lastly, both lPBN NK1R and elPBN neurons contribute to chemical irritant-induced nocifensive reactions. Our results reveal the functional organization of parabrachial substrates that drive distinct behavioral outcomes in response to sustained pain versus external danger under physiological conditions.

Traditionally, cytoarchitectonic area 3a of primary somatosensory cortex (SI) has been regarded as a proprioceptive relay to motor cortex. However, neuronal spike-train recordings and optical intrinsic signal imaging, obtained from nonhuman sensorimotor cortex, show that neuronal activity in some of the cortical columns in area 3a can be readily triggered by a C-nociceptor afferent drive. These findings indicate that area 3a is a critical link in cerebral cortical encoding of secondary/slow pain. Also, area 3a contributes to abnormal pain processing in the presence of activity-dependent reversal of gamma-aminobutyric acid A receptor-mediated inhibition. Accordingly, abnormal processing within area 3a may contribute mechanistically to generation of clinical pain conditions. PERSPECTIVE: Optical imaging and neurophysiological mapping of area 3a of SI has revealed substantial driving from unmyelinated cutaneous nociceptors, complementing input to areas 3b and 1 of SI from myelinated nociceptors and non-nociceptors. These and related findings force a reconsideration of mechanisms for SI processing of pain. [ABSTRACT FROM AUTHOR]

Gabapentin (GBP) is a first-line therapy for neuropathic pain, but its mechanisms and sites of action remain uncertain. We investigated GBP-induced modulation of neuropathic pain following spinal nerve ligation (SNL) in rats. Intravenous or intrathecal GBP reversed evoked mechanical hypersensitivity and produced conditioned place preference (CPP) and dopamine (DA) release in the nucleus accumbens (NAc) selectively in SNL rats. Spinal GBP also significantly inhibited dorsal horn wide-dynamic-range neuronal responses to a range of evoked stimuli in SNL rats. By contrast, GBP microinjected bilaterally into the rostral anterior cingulate cortex (rACC), produced CPP, and elicited NAc DA release selectively in SNL rats but did not reverse tactile allodynia and had marginal effects on wide-dynamic-range neuronal activity. Moreover, blockade of endogenous opioid signaling in the rACC prevented intravenous GBP-induced CPP and NAc DA release but failed to block its inhibition of tactile allodynia. Gabapentin, therefore, can potentially act to produce its pain relieving effects by (a) inhibition of injury-induced spinal neuronal excitability, evoked hypersensitivity, and ongoing pain and (b) selective supraspinal modulation of affective qualities of pain, without alteration of reflexive behaviors. Consistent with previous findings of pain relief from nonopioid analgesics, GBP requires engagement of rACC endogenous opioid circuits and downstream activation of mesolimbic reward circuits reflected in learned pain-motivated behaviors. These findings support the partial separation of sensory and affective dimensions of pain in this experimental model and suggest that modulation of affective-motivational qualities of pain may be the preferential mechanism of GBP's analgesic effects in patients. [ABSTRACT FROM AUTHOR]

Objective. The goal of the present study was to examine the relationship between pain and cognition in patients with multiple sclerosis. Design. Cross-sectional. Setting. Nursing home and personal environment of the investigators. Subjects. Two groups of participants were included: 91 patients with multiple sclerosis and 80 matched control participants. Methods. The level of pain was measured by the following pain scales: Number of Words Chosen-Affective, Colored Analogue Scale for pain intensity and suffering from pain, and the Faces Pain Scale. Mood was tested by administering the Beck Depression Inventory and the Symptom Check List-90 anxiety and depression subscale. Global cognitive functioning was assessed by the Mini Mental State Examination. Memory and executive functions were assessed by several neuropsychological tests. Results. Multiple sclerosis (MS) patients scored significantly lower than control participants on themajority of the neuropsychological tests. The MS patients experienced more pain compared with control participants, despite the fact that they were taking significantlymore painmedication.No significant correlation was observed between cognition and pain in MS patients. Verbal working memory explained 10% of pain intensity (trend). Mood appeared to be a significant predictorof pain in patientswithmultiple sclerosis. Conclusion. The lack of a relationship between cognition and pain might be explained by the fact that, compared with control participants, patients with multiple sclerosis activate other non-pain-related areas to perform executive functions and memory tasks. [ABSTRACT FROM AUTHOR]

Resilience, a characteristic that enhances adaptation in response to stressful events, is a positive psychological factor that can predict and modulate health outcomes. However, resilience is rarely considered in pain research. Conversely, negative psychological factors (eg, anxiety, depression) are known to be related to the affective dimension of pain. It is critical to understand all potential psychological drivers of pain affect, a prominent component of chronic pain. We tested the hypothesis that higher resilience is associated with lower pain affect, above and beyond the predictive value of negative psychological factors. Healthy adults underwent psychophysical testing to acquire ratings of heat pain intensity and unpleasantness and completed the Resilience Scale, the State-Trait Anxiety Inventory (trait form), Beck Depression Inventory, Pain Catastrophizing Scale, and the Pain Vigilance and Attention Questionnaire. Multiple regression modeling (n = 68) showed resilience to be a negatively associated with pain affect (unpleasantness). Furthermore, in individuals with higher anxiety scores, resilience was protective against higher pain affect. This highlights the importance of resilience, a positive psychological factor, in the affective dimension of pain. This study is the first to assess a positive psychological factor and experimental pain affect, and has the potential to improve prediction of and treatment strategies for clinical pain.Perspective: We report that resilience, a positive psychological factor, interacts with anxiety and is associated with heat pain affect (unpleasantness) in healthy individuals. Resilience may provide predictive value of chronic pain affect and treatment outcomes, and could be a target for behavioral therapy. [ABSTRACT FROM AUTHOR]

The neural network that contributes to the suffering which accompanies persistent pain states involves a number of brain regions. Of primary interest is the contribution of the cingulate cortex in processing the affective component of pain. The purpose of this review is to summarize recent data obtained using novel behavioral paradigms in animals based on measuring escape and/or avoidance of a noxious stimulus. These paradigms have successfully been used to study the nature of the neuroanatomical and neurochemical contributions of the anterior cingulate cortex to higher order pain processing in rodents.

Background In a previous study, the levels of pain reported by patients with 'possible' vascular dementia ( VaD) were higher than those reported by older individuals without dementia. Objective To examine experienced pain in patients with 'probable' VaD, confirmed by brain imaging. Study Design Observational, cross sectional. Setting Nursing home. Methods The participants were 20 nursing home residents (14 females, 6 males) who met the NINDS- AIREN criteria for 'probable' VaD and 22 nursing home residents with a normal mental status (18 females, 4 males). The patients were in a mild to moderate stage of dementia. All of the participants were suffering from arthritis/arthrosis or osteoporosis. Global cognitive functioning was measured by the Mini- Mental State Examination. Pain was assessed by the Coloured Analogue Scale ( CAS: original and modified version) and the Faces Pain Scale. The Geriatric Depression Scale and the Symptom Checklist-90 were used to assess mood. Results The main finding was that, after controlling for mood, the pain levels indicated by patients with 'probable' VaD (M = 102.32; standard deviation [ SD] = 53.42) were significantly higher than those indicated by the control group (M = 59.17; SD = 38.75), only according to the CAS modified version ( F[1,29]) = 5.62, P = 0.01, η2 = 0.16). Conclusion As VaD patients may experience greater pain than controls, it is essential for prescribers to be aware of the presence of this neuropathology if these patients are to receive adequate treatment. [ABSTRACT FROM AUTHOR]

The neural network that contributes to the suffering which accompanies persistent pain states involves a number of brain regions. Of primary interest is the contribution of the cingulate cortex in processing the affective component of pain. The purpose of this review is to summarize recent data obtained using novel behavioral paradigms in animals based on measuring escape and/or avoidance of a noxious stimulus. These paradigms have successfully been used to study the nature of the neuroanatomical and neurochemical contributions of the anterior cingulate cortex (ACC) to higher order pain processing in rodents. [ABSTRACT FROM AUTHOR]

Abstract: Pain is a private experience that involves both sensory and emotional components. Animal studies of pain can only be inferred by their responses, and therefore the measurement of reflexive responses dominates the pain literature for nearly a century. It has been argued that although reflexive responses are important to unveil the sensory nature of pain in organisms, pain affect is equally important but largely ignored in pain studies primarily due to the lack of validated animal models. One strategy to begin to understand pain affect is to use conditioning principles to indirectly reveal the affective condition of pain. This review critically analyzed several procedures that are thought to measure affective learning of pain. The procedures regarding the current knowledge, the applications, and their advantages and disadvantages in pain research are discussed. It is proposed that these procedures should be combined with traditional reflex-based pain measurements in future studies of pain, which could greatly benefit both the understanding of neural underpinnings of pain and preclinical assessment of novel analgesics. [Copyright &y& Elsevier]

The human experience of pain is multidimensional and comprises sensory, affective, and cognitive dimensions. Preclinical assessment of pain has been largely focused on the sensory features that contribute to nociception. The affective (aversive) qualities of pain are clinically significant but have received relatively less mechanistic investigation in preclinical models. Recently, operant behaviors such as conditioned place preference, avoidance, escape from noxious stimulus, and analgesic drug self-administration have been used in rodents to evaluate affective aspects of pain. An important advance of such operant behaviors is that these approaches may allow the detection and mechanistic investigation of spontaneous neuropathic or ongoing inflammatory/nociceptive (i.e., nonevoked) pain that is otherwise difficult to assess in nonverbal animals. Operant measures may allow the identification of mechanisms that contribute differentially to reflexive hypersensitivity or to pain affect and may inform the decision to progress novel mechanisms to clinical trials for pain therapy. Additionally, operant behaviors may allow investigation of the poorly understood mechanisms and neural circuits underlying motivational aspects of pain and the reward of pain relief. [ABSTRACT FROM AUTHOR]

This paper summarizes a behavioral paradigm that was developed as a novel method to dissociate the multidimensional pain experience in rodents. The place escape/avoidance paradigm (PEAP) is based on the assumption that if animals escape and/or avoid a noxious stimulus, then the stimulus is aversive to the animal. Data is presented showing that when animals are placed in a specific environmental condition, they will perform purposeful behavior to escape and/or avoid the noxious stimulus. Additional data is presented to demonstrate the validity of the behavioral paradigm and how the paradigm has been used to test the hypothesis that the affective/motivational dimension of pain can be dissociated and studied independent of sensory pain processing. The behavioral paradigm highlights the emerging trend in the area of pain research and management towards developing more realistic behavioral paradigms to assess nociceptive processing in rodent models of chronic pain. [ABSTRACT FROM AUTHOR]

Abstract: The place escape/avoidance paradigm (PEAP) is a behavioral test designed to quantify the level of unpleasantness evoked by painful stimuli by assessing the willingness of a subject to escape/avoid a preferred area when it is associated with noxious stimulation. Previous studies have demonstrated that escape/avoidance behavior is dependent on activity in the anterior cingulate cortex (ACC), a region of the limbic system involved in processing the emotional component of pain in humans and animals. Analysis of c-Fos expression in the ACC confirmed that the escape/avoidance response to noxious stimuli corresponds to changes in neural activation in this region. Behavioral tests such as the PEAP may be more sensitive to changes in supraspinal pain processing and could contribute to the development of novel analgesics in the future. [Copyright &y& Elsevier]

Abstract: In the preclinical study of pain, two commonly used pain models are the L5 spinal nerve ligation (SNL) and the injection of carrageenan. Using a modified place escape/avoidance paradigm (mPEAP), a novel behavioral test that quantifies aversive behavior evoked by painful stimuli, we directly compared the affective component of the SNL and inflammation models. Fifty three Sprague-Dawley rats underwent baseline mechanical paw withdrawal threshold (MPWT) and mPEAP testing followed by an L5 SNL or sham surgery for the left paw and then a carrageenan or saline injection for the right paw. After recovering, animals underwent post-manipulation MPWT and mPEAP tests. Both pain conditions produced mechanical hypersensitivity, and animals with a single-paw condition demonstrated escape/avoidance behavior in response to stimulation of the affected paw. Animals with the bilateral pain condition did not show a preference for stimulation of one paw versus the other paw, and the avoidance behavior was not significantly different from the sham/saline control. The results indicate that the pain models are associated with significant avoidance behavior and that they produce comparable degrees of pain affect. These findings advance the preclinical study of pain by validating the simultaneous utilization of the SNL and inflammation models and will allow future studies that combine pain conditions to more closely resemble clinical conditions. [Copyright &y& Elsevier]

Abstract: Studies of both humans and animals suggest that anterior cingulate cortex (ACC) is important for processing pain perception. We identified that perigenul ACC (pACC) sensitization and enhanced visceral pain in a visceral hypersensitive rat in previous studies. Pain contains both sensory and affective dimensions. Teasing apart the mechanisms that control the neural pathways mediating pain affect and sensation in nociceptive behavioral response is a challenge. In this study, using a rodent visceral pain assay that combines the colorectal distension (CRD)-induced visceromotor response (VMR) with the conditioning place avoidance (CPA), we measured a learned behavior that directly reflects the affective component of visceral pain. When CRD was paired with a distinct environment context, the rats spent significantly less time in this compartment on the post-conditioning test days as compared with the pre-conditioning day. Effects were lasted for 14days. Bilateral pACC lesion significantly reduced CPA scores without reducing acute visceral pain behaviors (CRD-induced VMR). Bilateral administration of non-NMDA receptor antagonist CNQX or NMDA receptor antagonist AP5 into the pACC decreased the CPA scores. AP5 or CNQX at dose of 400mM produced about 70% inhibition of CRD-CPA in the day 1, 4 and 7, and completely abolished the CPA in the day 14 after conditioning. We concluded that neurons in the pACC are necessary for the “aversiveness” of visceral nociceptor stimulation. pACC activation is critical for the memory processing involved in long-term negative affective state and prediction of aversive stimuli by contextual cue. [Copyright &y& Elsevier]

Abstract: Attachment theory has been proposed as a framework for understanding the development of chronic pain, with evidence supporting the overrepresentation of insecure attachment styles in chronic pain populations and links between insecure attachment and factors known to impact one’s ability to cope with pain. The present study sought to extend two earlier studies exploring the relationships between adult attachment and communication of an acute pain experience, in anticipation of providing insight into individual differences in vulnerability in development of chronic pain. It was hypothesised that: (a) fearful attachment would be associated with perceptions of the pain as less intense, and (b) anxious attachment would be associated with lower pain thresholds. A convenience sample of 82 healthy adults completed self-report measures of attachment, neuroticism, and negative affect prior to taking part in a coldpressor pain inducement task. Results demonstrated that fearful attachment was associated with lower levels of pain intensity throughout the coldpressor task. In addition, dismissing attachment was also associated with less intense pain, as well as increased coldpressor endurance (tolerance) in the presence of a known assessor. These associations were retained after controlling for measures of neuroticism, negative affect, age, and social desirability. The results of this study are consistent with the proposition that fearful and dismissing individuals tend to mask their underlying distress caused by the pain experience, potentially leading to difficulties coping with pain over time. [Copyright &y& Elsevier]

Abstract: In our previous studies, psychological stress was shown to enhance operant escape responding of male and female rats. The stressors that produced hyperalgesia were physical restraint and social defeat. Nociceptive input also elicits stress reactions, generating the prediction that pain would facilitate pain under certain circumstances. For example, the usual method of evaluating stress in laboratory animals is to test for effects after termination of the stressor. Accordingly, operant escape performance of male and female rats was evaluated during two successive trials involving nociceptive thermal stimulation. The intent was to determine whether nociceptive sensitivity differed on first trials and during pain-induced stress on second trials. Compared to a first trial of 44.5°C stimulation, escape responding increased during a second trial of 44.5°C stimulation (preceded by an escape trial of 10°C). Similarly, escape from cold (10°C) was enhanced when preceded by escapable 44.5°C stimulation. Thus, prior nociceptive stimulation enhanced escape from aversive thermal stimulation. Facilitation of pain by a preceding pain experience is consistent with stress-induced hyperalgesia and contrasts with other models of pain inhibition by concurrent nociceptive stimulation. [Copyright &y& Elsevier]

Abstract: NMDA receptors, which are implicated in pain processing, are highly expressed in forebrain areas including the anterior cingulate cortex (ACC). The ACC has been implicated in the affective response to noxious stimuli. Using a combination of immunohistochemical staining, Western blot, electrophysiological recording and formalin-induced conditioned place avoidance (F-CPA) rat behavioral model that directly reflects the affective component of pain, the present study examined formalin nociceptive conditioning-induced changes in the expressions of NMDA receptor subunits NR1, NR2A, and NR2B in the rostral ACC (rACC) and its possible functional significance. We found that unilateral intraplantar (i.pl.) injection of dilute formalin with or without contextual conditioning exposure markedly increased the expressions of NMDA receptor subunits NR2A and NR2B but not of NR1 in the bilateral rACC. NMDA-evoked currents in rACC neurons were significantly greater in formalin-injected rats than in naïve or normal saline-injected rats. Selectively blocking either NR2A or NR2B subunit in the rACC abolished the acquisition of F-CPA and formalin nociceptive conditioning-induced Fos expression, but it did not affect formalin acute nociceptive behaviors and non-nociceptive fear stimulus-induced CPA. These results suggest that both NMDA receptor subunits NR2A and NR2B in the rACC are critically involved in pain-related aversion. Thus, a new strategy targeted at NMDA NR2A or NR2B subunit might be raised for the prevention of pain-related emotional disturbance. [Copyright &y& Elsevier]

Abstract: Attachment relationships shape the manner in which children signal pain to others. Open communication of pain affect, inhibition of pain affect, and exaggeration of pain affect, reflect adaptations to different relationship contexts. The open and direct signaling of pain is adaptive in sensitive relationship contexts where caregivers respond to the distressed child with behaviors that facilitate protection, recovery, and healing. Inhibition of pain signals has survival advantages in situations where the open expressions of pain elicit negative parental responses (absence of caregiving, withdrawal from the child, or frank displeasure or anger). Exaggerated pain signaling functions as a means to elicit a caregiving response from preoccupied, inattentive, or neglectful attachment figures. This paper considers how a child''s developmental experiences—specifically, the repeating person-specific experiences which make up attachment relationships—produce individual differences in the manner in which pain is experienced and signaled. Perspective: This article reviews recent advances in our understanding of child development as articulated by contemporary attachment theory—in particular, the dynamic-maturational model (DMM)—and discusses their implications for interpreting human pain, pain-signaling behavior, and medically unexplained pain. The development of the experience of pain, along with ways of signaling pain, is tied to familial relationships generally and, in particular, to the manner in which attachment relationships shape the infant''s behavior and physiology, thereby regulating the experience of pain. In explaining how the child''s early attachment relationships produce individual differences in the way that she learns to experience and signal pain, the article provides an innovative perspective that is helpful in understanding the wide variations in patients'' experience and presentation of pain, in elaborating formulations of medically unexplained pain, and in planning treatment. More broadly, the article suggests a variety of hypotheses for further empirical testing. [Copyright &y& Elsevier]

Poor sleep quality is often comorbid with chronic pain. Research has also shown that poor and disrupted sleep may increase risk for chronic pain by promoting pronociceptive processes. This could occur through disrupted emotional modulation of pain since poor sleep can impact emotional experience and emotional experience modulates pain and nociception. To assess the pain system, nociceptive flexion reflexes (spinal level), pain-evoked potentials (supraspinal level), and perceived pain were recorded during an emotional picture-viewing task in which 37 healthy individuals received painful electric stimulations. The Pittsburgh Sleep Quality Index assessed sleep quality. Individuals with poor sleep quality were unable to inhibit signals at the spinal level in response to positive pictures, whereas emotional modulation of supraspinal nociception and pain perception remained unaffected by sleep quality. This suggests poor sleep quality may promote pronociception by impairing descending, emotional modulation of spinal nociception. • Poor sleep quality may increase risk for chronic pain through emotion disruption. • Emotion modulates pain at spinal, supraspinal, and perceptual levels. • The impact of sleep on emotion modulation of pain across the neuraxis is unclear. • Sleep quality disrupts descending inhibition of spinal nociception. • Sleep quality did not disrupt modulation of pain or supraspinal nociception. [ABSTRACT FROM AUTHOR]

Abstract: The parafascicular nucleus (nPf) of the intralaminar thalamus is implicated in the processing of pain affect in both animals and humans. Administration of morphine into nPf results in preferential suppression of the affective reaction to noxious tail shock in rats. The involvement of the ventrolateral periaqueductal gray in mediating the antinociceptive action of morphine injected into nPf was evaluated. Vocalizations that occur after tail shock offset (vocalization afterdischarges) are a validated rodent model of pain affect and were preferentially suppressed by injection of morphine into nPf. Vocalizations that occur during tail shock were suppressed to a lesser degree, whereas spinal motor reflexes (tail flick and hind limb movements) were unaffected by injection of morphine into nPf. Inactivation of the vPAG via the microinjection of muscimol (GABAA agonist) produced dose-dependent antagonism of morphine-induced increases in vocalization thresholds. The results demonstrate that a functional link between the nPf and vPAG in generating the antinociceptive action of morphine injected into nPf. Perspective: Microinjection of morphine into nucleus parafascicular preferentially suppressed rats'' affective reaction to noxious stimulation. This affective analgesia was reversed by inactivation of the ventrolateral periaqueductal gray. Understanding the neurobiology underlying the suppression of pain affect will provide insights into new treatments for pain and its associated affective disorders. [Copyright &y& Elsevier]

Abstract: Signs and symptoms of persistent pain are associated with neuronal hyperexcitability within nociceptive pathways. This manifests behaviourally as a decrease in the nociceptive threshold to sensory stimulation, and is closely correlated with altered affective pain processing and increased expression of anxiety-like symptoms. Anticonvulsant drugs can have marked analgesic actions in animals and humans, and some have also been reported to possess anxiolytic-like properties in animals. In the current study, we have compared the antinociceptive actions of diazepam (allosteric GABAA receptor modulator), gabapentin (binds to α2δ Ca2+ channel subunit), lamotrigine, riluzole and phenytoin (Na+ channel blockers), levetiracetam (unknown mechanism), sodium valproate (potentiates GABA-mediated inhibition), ethosuximide (T-type Ca2+ channel blocker) and retigabine (Kv7 channel opener) in the rat formalin test, with their anxiolytic actions in the rat conditioned emotional response (CER) model of anxiety. Lamotrigine, gabapentin, riluzole, retigabine and ethosuximide attenuated second phase nociceptive responses in the formalin test. Lamotrigine, gabapentin and riluzole also displayed an anxiolytic-like profile in the CER model. Notably, the minimum doses of these drugs required to attenuate anxiety behaviour were similar to, or considerably lower than those needed to reverse pain-like behaviours. Diazepam was anxiolytic but only attenuated pain-like behaviours at sedative doses. The other drugs tested were inactive in both models. Our data suggests: (i) an antiepileptic mechanism of action per se is not necessarily sufficient for a compound to display antinociceptive and/or anxiolytic actions; and (ii) the combined antinociceptive and anxiolytic-like profiles of lamotrigine, gabapentin and riluzole suggests that these compounds likely modulate both sensory and affective dimensions of pain. [Copyright &y& Elsevier]

Abstract: Since aging is a risk factor for both dementia and the occurrence of painful conditions, with the number of aged people increasing in the next decades, an increase in the number of elderly people suffering from both conditions can be anticipated. Reliable pain assessment in this population is restricted by reduced communicative and cognitive capacity, with serious consequences for effective pain treatment. White matter changes are frequently observed in the various subtypes of dementia as well as in normal aging, and may play a crucial role in pain processing. In healthy elderly people, reliable pain assessment can be accomplished, which enables examining the relationship between pain experience and white matter changes. A normal structure and function of the white matter is extremely important for dorsolateral prefrontal cortex (DLPFC) functioning, which has recently been linked to pain inhibition. The present study focused on the relation between white matter changes and both pain intensity and pain affect in elderly people without dementia. The Coloured Analogue Scale (CAS) and the Number of Words Chosen-Affective (NWC-A) were applied to measure pain intensity and pain affect, respectively. The presence of white matter changes was significantly related to a higher score on the NWC-A but not the CAS score. These results suggest that pain experience may change as a result of aging and that white matter changes might be indicative for these alterations. [Copyright &y& Elsevier]

Abstract: The affective and the sensory dimensions of pain processing can be differentiated in humans through the use of questionnaires and verbal communication. It is difficult to dissociate these two components of pain processing in rodents, and an understanding of the underlying mechanisms for each component is unclear. The quantification of a novel behavioral response to a repeated noxious cutaneous stimulus together with a measurement of tactile allodynia in nerve-injured rats might be used to differentially explore the sensory and affective components of pain processing in the rat. The present study utilized electrical stimulation of the anterior cingulate cortex, a structure implicated in affective pain processing but not sensory processing, in nerve-injured rats (L5 spinal nerve ligation) and found that the aversive quality of noxious cutaneous hindpaw stimulation was attenuated. There were no effects on sensory processing, because anterior cingulate cortex stimulation did not produce an anti-allodynic effect in L5 spinal nerve ligation animals. Furthermore, anterior cingulate cortex stimulation in animals with bilateral ventrolateral periaqueductal gray area lesions did not affect tactile sensitivity in L5 spinal nerve ligation rats, indicating that an endogenous pain suppression system was not likely activated by anterior cingulate cortex stimulation. However, bilateral ventrolateral periaqueductal gray area lesions in L5 spinal nerve ligation rats blocked the effect produced by anterior cingulate cortex stimulation in the place escape/avoidance paradigm. Specifically, these animals avoided noxious stimulation of the allodynic paw significantly more than anterior cingulate cortex-stimulated, sham or incomplete ventrolateral periaqueductal gray area-lesioned, L5 spinal nerve ligation animals. These findings provide the first quantified report that the activation of the anterior cingulate cortex reduced the aversive quality of repeated noxious tactile stimulation in nerve-injured animals without interfering with normal sensory processing. This effect might require the presence of an intact ventrolateral periaqueductal gray area. It is concluded that the selective manipulation of the anterior cingulate cortex has different effects on pain affect and sensory processing in a rodent model of neuropathic pain. [Copyright &y& Elsevier]

Abstract: The effect of emotions on pain perception is generally recognized but the underlying mechanisms remain unclear. Here, emotions related to pain were induced in healthy volunteers using hypnosis, during 1-min immersions of the hand in painfully hot water. In Experiment 1, hypnotic suggestions were designed to induce various positive or negative emotions. Compared to a control condition with hypnotic-relaxation, negative emotions produced robust increases in pain. In Experiment 2, induction of pain-related anger and sadness were found to increase pain. Pain increases were associated with increases in self-rated desire for relief and decreases in expectation of relief, and with increases in arousal, negative affective valence and decreases in perceived control. In Experiment 3, hypnotic suggestions specifically designed to increase and decrease the desire for relief produced increases and decreases in pain, respectively. In all three experiments, emotion-induced changes in pain were most consistently found on ratings of pain unpleasantness compared to pain intensity. Changes in pain-evoked cardiac responses (R–R interval decrease), measured in experiments 2 and 3, were consistent with changes in pain unpleasantness. Correlation and multiple regression analyses suggest that negative emotions and desire for relief influence primarily pain affect and that pain-evoked autonomic responses are strongly associated with pain affect. These results confirm the hypothesized influence of the desire for relief on pain perception, and particularly on pain affect, and support the functional relation between pain affect and autonomic nociceptive responses. This study provides further experimental confirmation that pain-related emotions influence pain perception and pain-related physiological responses. [Copyright &y& Elsevier]

The present experiment examined the possibility to change the sensory and/or the affective perception of thermal stimuli by an emotional associative learning procedure known to operate without participants'' awareness (evaluative conditioning). In a mixed design, an aversive conditioning procedure was compared between subjects to an appetitive conditioning procedure. Both groups were also compared within-subject to a control condition (neutral conditioning). The aversive conditioning was induced by associating non-painful and painful thermal stimuli – delivered on the right forearm – with unpleasant slides. The appetitive conditioning consisted in an association between thermal stimuli – also delivered on the right forearm – and pleasant slides. The control condition consisted in an association between thermal stimuli – delivered for all participants on the left forearm – and neutral slides. The effects of the conditioning procedures on the sensory and affective dimensions were evaluated with visual analogue scale (VAS)-intensity and VAS-unpleasantness. Startle reflex was used as a physiological index of emotional valence disposition. Results confirmed that no participants were aware of the conditioning procedure. After unpleasant slides (aversive conditioning), non-painful and painful thermal stimuli were judged more intense and more unpleasant than when preceded by neutral slides (control condition) or pleasant slides (appetitive conditioning). Despite a strong correlation between the intensity and the unpleasantness scales, effects were weaker for the affective scale and, became statistically non-significant when VAS-intensity was used as covariate. This experiment shows that it is possible to modify the perception of intensity of thermal stimuli by a non-conscious learning procedure based on the transfer of the valence of the unconditioned stimuli (pleasant or unpleasant slides) towards the conditioned stimuli (non-painful and painful thermal stimuli). These results plead for a conception of pain as a conscious output of complex informational processes all of which are not accessible to participants'' awareness. Mechanisms by which affective input may influence sensory experience and clinical implications of the present study are discussed. [Copyright &y& Elsevier]

Nos propos soutiennent une conception de la douleur en tant que produit final d’un processus perceptif complexe et global (le percept) au cours duquel le message nociceptif subit de nombreuses modulations centrales qui échappent à la conscience. En s’appuyant sur des exemples, nous verrons que, comme pour les autres modalités sensorielles, l’accès au stimulus qui déclenche la perception douloureuse, ainsi que le traitement de l’information dont celui-ci fait l’objet, sont influencés par de nombreux facteurs psychologiques (attentionnels, motivationnels, émotionnels, d’apprentissage, etc.). Nous étudierons, en particulier, l’impact des émotions sur la perception nociceptive. Une brève revue de la littérature sera complétée par des observations expérimentales originales qui traitent du cas particulier, encore mal connu, de l’influence des processus émotionnels inconscients sur le traitement de l’information nociceptive. Les expériences animales du conditionnement par la peur et les expériences humaines du conditionnent évaluatif, suggèrent que les caractéristiques affectives et sensorielles de la douleur pourrainent être encodées dans le système nerveux central d’une façon associative, non consciente et indélébile. Nos travaux ont montré que l’association répétée entre un stimulus nociceptif (le stimulus conditionné) et des stimulus inconditionnels (des images de valence émotionnelle positive ou négative), peut modifier la perception de ce stimulus nociceptif lorsqu’il est présenté ultérieurement dans un contexte émotionnellement neutre, et, que cet apprentissage est resté inconscient. En guise de conclusion, nous proposerons une définition des caractéristiques émotionnelles du système dédicacé au traitement de l’information nociceptive. This review supports a conception of pain as the final outcome of a complex and global perceptive process (the percept) during which the nociceptive message is subjected to a large amount of central modulations escaping consciousness. Based on examples, we shall see that, as for other sensory modalities, access to the stimulus that triggers the painful percept, as wall as the processing of it, is influenced by a number of psychological factors (attention, motivation, emotion, learning, ...). We shall examine, in particular, the impact of emotions on nociceptive perception. A brief review of the literature shall be extended by original experimental contributions, which concern the particular case, yet poorly understood, of the influence of unconscious emotional processes on the processing of nociceptive information. Animal experiments of fear conditioning and human experiments of evaluative conditioning suggest that the affective and sensorial characteristics of pain may be encoded in the central nervous system in a way that is associative, unconscious and indelible. Our experimental studies show that the repeated association between a nociceptive stimulus (the conditioned stimulus) and unconditioned stimuli (images of positive or negative emotional valence), may modify the perception of that nociceptive stimulus when it is presented subsequently in a neutral emotional context, and that this learning process remained unconscious. We shall conclude by proposing a definition of the emotional characteristics of the system dedicated to the processing of nociceptive information. [ABSTRACT FROM AUTHOR]

College students (25 men and 25 women) were randomly assigned (within sex) to each of the 4 factorial groups, based on manipulation of affect quality (positive vs. negative) and directional focus (internal vs. external) of mental imagery, and to a control group receiving no manipulation. Both imagery variables had a significant impact on pain tolerance and ratings during a cold-pressor test with positive affect and external imagery producing greater analgesia than their counterpart conditions. Positive affect imagery combined with external imagery resulted in the lowest reported pain amongst the groups. However, self-reported mood descriptors did not consistently parallel the pain tolerance and rating data. Likewise, although heart rate and skin potential responses increased during the cold pressor for the group as a whole, the only significant difference amongst the experimental groups was the relatively higher skin potential reactivity of the positive affect-external imagery group—possibly reflecting greater task engagement for this group. Seemingly, imagery in this situation operates primarily via cognitive, rather than via physiological mediators of the pain experience. [ABSTRACT FROM AUTHOR]

Background: In earlier studies, pain assessment in patients with Alzheimer's disease (AD) was conducted by interview, for which reliability is questionable considering the decline in expressive and receptive language abilities in AD. As similar language problems occur in young children, the reliability of pain assessment in this latter population is increased by employing visual analogue scales.Objective: By employing visual analogue scales, the current study investigated whether (1) nondemented elderly persons and AD patients comprehend the purpose of the scales and (2) AD patients, compared to nondemented elderly persons, report suffering less pain intensity and pain affect.Methods: Three visual analogue scales, i.e. the Colored Analogue Scale (CAS), the Faces Pain Scale (FPS), and the Facial Affective Scale (FAS) were administered to patients in an early and midstage of AD and to nondemented elderly persons.Results: The results show that the percentage of subjects who comprehended the CAS, FAS and FPS was for the nondemented elderly persons 100, 75 and 100%, respectively, for the early AD group 100, 50 and 60%, respectively, and for the midstage AD group 80, 20 and 30%, respectively. Furthermore, elderly persons without dementia reported experiencing more intense pain and pain affect than the early and midstage AD group. Interestingly, the early and midstage AD patients did not differ in reporting pain affect.Conclusion: Visual analogue scales may improve pain assessment in those AD patients who fully comprehend the meaning of the scales. As only the minority of midstage AD patients understood the purpose of the FAS and FPS, the search for tools, particularly to assess pain affect in this population, must continue. [ABSTRACT FROM AUTHOR]