Plastic changes in spinal cord function like neuronal wind-up and increased receptive field are too short-lived to explain chronic pain without structural changes. It is possible that learning could be a mechanism for longlasting changes in nociceptive regulation. A learning process localized to the spinal cord has been shown to be important for the development of tolerance to the analgetic effect of ethanol, suggesting that nociceptive control systems may be changed by learning. Long term potentiation (LTP) is regarded as a (...) useful model of learning and memory. LTP-like changes have been observed in invitro preparations from the spinal cord and in spinal cord field potentials. Recently a long term increase in spinal A-[beta] and C-fibre evoked responses after painful stimulation has been observed. [coderre & katz, dickenson, wiesenfeld-hallin et al.]. (shrink)

Central sensitization and related neurochemical mechanisms are also induced in V nociceptive pathways after craniofacial injury or inflammation. Their characteristics raise additional possibilities that may explain some of the phenomena outlined by coderre & katz, dickenson, and wiesenfeld-hallin et al. They also underscore the need for therapeutic approaches to reduce nociceptive inputs to the CNS or their neuroplastic effects which can potentially enhance post-traumatic pain.

There are some conspicuous differences between the sensibilities of cutaneous and visceral tissues: (1) Direct trauma, which readily produces pain when applied to the skin, is mostly without effect in healthy visceral tissue. (2) Pain that arises from visceral tissues is initially often poorly localised and diffuse. (3) With time, visceral pains are often referred to more superficial structures. (4) The site of referred pain may also show hyperalgesia. (5) In disease states, the afflicted viscera may also become hyperalgesic. In (...) this target article, I consider to what extent differences in the physiology, anatomy, and chemistry of peripheral processing systems explain these different sensibilities. In almost every aspect, there are subtle differences in the properties of the processing mechanisms for cutaneous and visceral information. These may arise because of distinct developmental cues operating in the two domains. Many of the differences between visceral and cutaneous afferents are quantitative rather than qualitative. The quantitative differences, for example in the density of afferent innervation, can be large. The quantitative differences in the numbers of afferents alone may be a sufficient explanation for some aspects of the differential sensibility, for example, the poor localisation of sensation and the apparent insensitivity to focal yet tissue- damaging stimuli. In addition, the few clear qualitative differences apparent in the innervations of the two tissue types may be of special importance. That the encoding of visceral nociceptive events may occur by an intensity mechanism rather than a specificity mechanism could be the key difference in viscerosensory and somatosensory processing. (shrink)

In 1925, David Katz published an influential monograph on touch, Der Aufbau der Tastwelt, which was translated into English in 1989. Although it is called “the world of touch,” it also discusses the thermal and the nociceptive senses, albeit briefly. In this chapter, we will follow this approach, but we will speak about “somatosensory senses” in general in order to remind ourselves that perceptions of temperatures and pains should also be considered together in this context.

Central sensitization refers to the increased responsiveness of nociceptive neurons in the central nervous system after repeated or sustained peripheral nociceptor activation. It is hypothesized to play a key role in the development of chronic pain. A hallmark of central sensitization is an increased sensitivity to noxious mechanical stimuli extending beyond the injured location, known as secondary hyperalgesia. For its ability to modulate the transmission and the processing of nociceptive inputs, attention could constitute a promising target to prevent central sensitization (...) and the development of chronic pain. It was recently shown that the experimental induction of central sensitization at both forearms of healthy volunteers using bilateral high-frequency electrocutaneous stimulation (HFS), can be modulated by encouraging participants to selectively focus their attention to one arm, to the detriment of the other arm, resulting in a greater secondary hyperalgesia on the attended arm as compared to the unattended one. Given the potential value of the question being addressed, we conducted a preregistered replication study in a well-powered independent sample to assess the robustness of the effect, i.e., the modulatory role of spatial attention on the induction of central sensitization. This hypothesis was tested using a double-blind, within-subject design. Sixty-seven healthy volunteers performed a task that required focusing attention toward one forearm to discriminate innocuous vibrotactile stimuli while HFS was applied on both forearms simultaneously. Our results showed a significant increase in mechanical sensitivity directly and 20 min after HFS. However, in contrast to the previous study, we did not find a significant difference in the development of secondary hyperalgesia between the attended vs. unattended arms. Our results question whether spatial selective attention affects the development of secondary hyperalgesia. Alternatively, the non-replication could be because the bottom-up capture of attention caused by the HFS-mediated sensation was too strong in comparison to the top-down modulation exerted by the attentional task. In other words, the task was not engaging enough and the HFS pulses, including those on the unattended arm, were too salient to allow a selective focus on one arm and modulate nociceptive processing. (shrink)

It has been 35 years since the publicationMelzack and Wall's Gate Control Theory whichhypothesized that nociceptive information wassubject to dynamic regulation by mechanismslocated in the spinal cord dorsal horn thatcould ultimately lead to hyperalgesic orhypoalgesic states. This paper examines GateControl Theory in light of our currentunderstanding of the neuroanatomical,neurophysiological and neurochemical substratesof nociception and antinociception. Despiteits initial controversies, no one has proposeda more comprehensive overall theory of painmodulation or has successfully refuted most ofthe basic tenets of this theory.

There is a fundamental inconsistency in Western society’s treatment of non-human animals on the one hand, and of human foetuses on the other. While most Western countries allow the butchering of animals and their use in experimentation, this must occur under carefully controlled conditions that are intended to minimize their pain and suffering as much as possible. At the same time, most Western countries permit various abortion methods without similar concerns for the developing fetus. The only criteria for deciding which (...) abortion method is used centre in the stage of the pregnancy, the size of the fetus, the health of the pregnant woman and the physician’s preference. This is out of step with the underlying ethos of animal cruelty legislation, cannot be justified ethically and should be rectified by adjusting abortion methods to the capacity of the fetus to experience nociception and/or pain. (shrink)

The peripheral nervous system has classically been separated into a somatic division composed of both afferent and efferent pathways and an autonomic division containing only efferents. J. N. Langley, who codified this asymmetrical plan at the beginning of the twentieth century, considered different afferents, including visceral ones, as candidates for inclusion in his concept of the “autonomic nervous system”, but he finally excluded all candidates for lack of any distinguishing histological markers. Langley's classification has been enormously influential in shaping modern (...) ideas about both the structure and the function of the PNS. We survey recent information about the PNS and argue that many of the sensory neurons designated as “visceral” and “somatic” are in fact part of a histologically distinct group of afferents concerned primarily autonomic function. These afferents have traditionally been known as “small dark” neurons or B-neurons. In this target article we outline an association between autonomic and B-neurons based on ontogeny, cell phenotype, and functional relations, grouping them together as part of a common reflex system involved in homeostasis. This more parsimonious classification of the PNS, made possible by the identification of a group of afferents associated primarily with the ANS, avoids a number of confusions produced by the classical orientation. It may also have practical implications for an understanding of nociception, homeostatic reflexes, and the evolution of the nervous system. (shrink)

Various prominent theories of pain assume that it is pain’s biological function to inform organisms about damage to their bodies. I argue that this is a mistake. First, there is no biological evidence to support the notion that pain was originally selected for its informative capacities, nor that it currently contributes to the fitness of organisms in this specific capacity. Second, neurological evidence indicates that modulating mechanisms in the nociceptive system systematically prevent pain from serving a primarily informative role. These (...) considerations threaten to undermine standard perceptual and representational accounts of pain. (shrink)

In this paper we1 assess the potential for research on nonhuman animals to address questions about the phenomenology of painful experiences. Nociception, the basic capacity for sensing noxious stimuli, is widespread in the animal kingdom. Even rel- atively primitive animals such as leeches and sea slugs possess nociceptors, neurons that are functionally specialized for sensing noxious stimuli (Walters 1996). Vertebrate spinal cords play a sophisticated role in processing and modulating nociceptive signals, providing direct control of some motor responses to (...) noxious stimuli, and a basic capacity for Pavlovian and instrumental conditioning (Grau et al. 1990; Grau 2002). Higher brain systems provide additional layers of association, top-down control, and cognition. In humans, at least, these higher brain systems also give rise to the conscious experiences that are characteristic of pain. What can be said about the experiences of other animals who possess nervous systems that are similar but not identical to humans? (shrink)

Why are de se mental states essential? What exactly is their de se-ness needed to do? I argue that it is needed to fend off accidentalness. If certain beliefs – for example, nociceptive, proprioceptive or introspective beliefs – were not de se, then any truth they achieved would be too accidental for the subject to count as knowing. If certain intentions – intentions that are in play whenever we intentionally do anything – were not de se, then any satisfaction they (...) achieved would be too accidental for the subject to count as intentionally acting. How states hook on to their referent is relevant in a systematic but underexplored way to whether they non-accidentally achieve their aim – truth in the case of beliefs, satisfaction in the case of intentions. In the relevant cases, the way of hooking on to a referent needed to avoid being accidental is the way a de se state hooks on to its referent. (shrink)

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. (shrink)

Which nonhuman animals experience conscious pain?1 This question is central to the debate about animal welfare, as well as being of basic interest to scientists and philosophers of mind. Nociception—the capacity to sense noxious stimuli—is one of the most primitive sensory capacities. Neurons functionally specialized for nociception have been described in invertebrates such as the leech Hirudo medicinalis and the marine snail Aplysia californica (Walters 1996). Is all nociception accompanied by conscious pain, even in relatively primitive animals (...) such as Aplysia, or is it the case, as some philosophers continue to maintain, that conscious experiences are the exclu- sive province of human beings? What philosophical and scientific resources are presently available for assessing claims lying between these extremes? (shrink)

My paper challenges an influential distinction between pain and suffering put forward by physician-ethicist, Eric Cassell. I argue that Cassell’s distinction is philosophically untenable because he contrasts suffering with an outdated theory of pain. In particular, Cassell focuses on one type of pain, the interpretation of nociception induced by noxious stimuli such as heat or sharp objects; yet since the late 1970s, pain scientists have rendered both nociception and noxious stimuli unnecessary for pain. I argue that this discrepancy (...) between Cassell’s distinction and pain science produces three philosophical problems for his distinction: first, he frames his distinction too generally, concentrating on only one type of pain to the neglect of others, such as neuropathy; second, it is possible that Cassell’s understanding of pain may include suffering; and third, Cassell gives examples of pain and suffering manifesting independently of each other, but it is possible that these cases may instead exemplify differences between nociceptive and non-nociceptive types of pain. Due to these problems, I conclude that Cassell’s distinction currently lacks a difference. I call for new efforts to articulate the differences, if any, between pain and suffering. (shrink)

Health care providers are expected both to relieve pain and to provide anticipatory guidance regarding how much a procedure is going to hurt. Fulfilling those expectations is complicated by the cognitive modulation of pain perception. Warning people to expect pain or setting expectations for pain relief not only influences their subjective experience, but it also alters how nociceptive stimuli are processed throughout the sensory and discriminative pathways in the brain. In light of this, I reconsider the characterization of placebo analgesia (...) as pharmacologically inert and the use of it as deceptive. I show that placebo analgesia exploits the same physical mechanisms as proven analgesics and argue that it should be utilized to relieve pain. Additionally, I describe factors to help identify situations in which clinicians have the obligation to disclose the potential for pain coupled with ways of mitigating the risk of high-intensity pain by setting positive expectations. (shrink)

When you suffer a pain are you suffering a sensation? An emotion? An aversion? Pain typically has all three components, and others too. There is indeed a distinct sensory system devoted to pain, with its own nociceptors and pathways. As a species of somesthesis, pain has a distinctive sensory organization and its own special sensory qualities. I think it is fair to call it a distinct sensory modality, devoted to nociceptive somesthetic discrimination. But the typical pain kicks off other processes (...) too. For one it can grab your attention in a distinctive way, alerting you to its presence and sometimes obliging you to focus attention on the damaged member. Intense pain can eliminate your ability to think about anything else. Pain typically has direct and immediate motivational consequences: one wants it to stop, has an incentive to do whatever one can to reduce it, and is gratified by its termination. As these desires and motives collide with neural reality, emotional components of mental anguish, anxiety, and dread arise. The suffering involved in suffering from pain has multiple strands: it is not just the painfulness of the sensation, or the frustration of the desire that it end, but also the anguish over the possibility that it will never end, and the impossibility, if the pain is sufficiently intense, of focusing one’s attention on anything else. (shrink)

My account of the causal role of consciousness in a physical world is modeled on Dretske’s celebrated explanation of the causal role of beliefs (something that Dretske himself never offered). First, behavior must be understood as a (broadly individuated) process that begins with some external stimulus causing some neurological event C, and ends with causing a bodily movement M (e.g., the Kennedy assassination is a process that begins with Oswald pulling the trigger at 12:30pm CST on November 23 in 1963 (...) in Dallas, Texas, but only ends half an hour later when Kennedy is pronounced dead at 1 pm CST). The internal neurological event C causes bodily movement M, but only by virtue of being recruited by natural selection to represent the instantiation of some external property F when properly stimulated under normal circumstances. But the reason why C causes M lies in the fact that C represents the instantiation of the external property F. I withdraw my hand from a hot surface because the activation of nociceptive specific neurons in my parietal lobe (together with the activation of neuronal patterns in my motor cortices) was recruited by natural selection to represent the tissue damage in my hand. The activation of nociceptive specific neurons causes my hand to withdraw but for the reason that it represents tissue data at the time that I felt pain in my hand. (shrink)

We attempt to bring the concepts of pain, suffering, and anxiety into sufficient focus to make them serviceable for empirical investigation. The common-sense view that many animals experience these phenomena is supported by empirical and philosophical arguments. We conclude, first, that pain, suffering, and anxiety are different conceptually and as phenomena, and should not be conflated. Second, suffering can be the result — or perhaps take the form — of a variety of states including pain, anxiety, fear, and boredom. Third, (...) pain and nociception are not equivalent and should be carefully distinguished. Fourth, nociception can explain the behavior of insects and perhaps other invertebrates (except possibly the cephalopods). Fifth, a behavioral inhibition system associated with anxiety in humans seems to be present in mammals and most or all other vertebrates. Based on neurochemical and behavioral evidence, it seems parsimonious to claim that these animals are capable of experiencing anxious states. (shrink)

Philosophical (p-) zombies are constructs that possess all of the behavioral features and responses of a sentient human being, yet are not conscious. P-zombies are intimately linked to the hard problem of consciousness and have been invoked as arguments against physicalist approaches. But what if we were to invert the characteristics of p-zombies? Such an inverse (i-) zombie would possess all of the behavioral features and responses of an insensate being yet would nonetheless be conscious. While p-zombies are logically possible (...) but naturally improbable, an approximation of i-zombies actually exists: individuals experiencing what is referred to as “anesthesia awareness.” Patients under general anesthesia may be intubated (preventing speech), paralyzed (preventing movement), and narcotized (minimizing response to nociceptive stimuli). Thus, they appear—and typically are—unconscious. In 1-2 cases/1000, however, patients may be aware of intraoperative events, sometimes without any objective indices. Furthermore, a much higher percentage of patients (22% in a recent study) may have the subjective experience of dreaming during general anesthesia. P-zombies confront us with the hard problem of consciousness—how do we explain the presence of qualia? I-zombies present a more practical problem—how do we detect the presence of qualia? The current investigation compares p-zombies to i-zombies and explores the “hard problem” of unconsciousness with a focus on anesthesia awareness. (shrink)

While unnecessarily killing or injuring an insect is arguably wrong, euthanasia of an accidentally injured insect raises anew issues of whether insects can experience pain. The question takes renewed significance due to increasing insect farming for food and feed and concerns over farmed insect welfare. For euthanasia of a damaged insect to be justifiable, the damage must be sensed as a noxious stimulus (nociception) that the insect consciously experiences as pain. This pain must then lead to suffering or frustrated (...) desire, with the possibility of the animal preferring death to continued existence. A failure at any of these points would deem euthanasia moot. The neurological, behavioral, and evolutionary evidence so far suggests the concept of euthanasia does not apply to insects. (shrink)

Automatic control of physiological variables is one of the most active areas in biomedical engineering. This paper is centered in the prediction of the analgesic variables evolution in patients undergoing surgery. The proposal is based on the use of hybrid intelligent modelling methods. The study considers the Analgesia Nociception Index to assess the pain in the patient and remifentanil as intravenous analgesic. The model proposed is able to make a one-step-ahead prediction of the remifentanil dose corresponding to the current (...) state of the patient. The input information is the previous remifentanil dose, the ANI variable and the electromyogram signal. Modelling techniques used are Artificial Neural Networks and Support Vector machines for Regression combined with clustering methods. Both training and validation were done with a real dataset from different patients. Results obtained show the potential of this methodology to calculate the drug dose corresponding to a given analgesic state of the patient. (shrink)

Intradermal capsaicin in humans causes pain, primary hyperalgesia, and secondary mechanical hyperalgesia and allodynia. Parallel changes occur in the responses of primate spinothalamic tract cells and in rat behavior. Neurotransmitters that trigger secondary mechanical hyperalgesia and allodynia include excitatory amino acids and substance P. Secondary mechanical allodynia is actively maintained by central mechanisms. Our group has investigated mechanisms of central sensitization of nociceptive neurons by examining the responses to intradermal injection of capsaicin. These experiments are pertinent to issues raised by (...) coderre & katz (sect. 2). (shrink)

One of the main challenges in medicine is to guarantee an appropriate drug supply according to the real needs of patients. Closed-loop strategies have been widely used to develop automatic solutions based on feedback variables. However, when the variable of interest cannot be directly measured or there is a lack of knowledge behind the process, it turns into a difficult issue to solve. In this research, a novel algorithm to approach this problem is presented. The main objective of this study (...) is to provide a new general algorithm capable of determining the influence of a certain clinical variable in the decision making process for drug supply and then defining an automatic system able to guide the process considering this information. Thus, this new technique will provide a way to validate a given physiological signal as a feedback variable for drug titration. In addition, the result of the algorithm in terms of fuzzy rules and membership functions will define a fuzzy-based decision system for the drug delivery process. The method proposed is based on a Fuzzy Inference System whose structure is obtained through a decision tree algorithm. A four-step methodology is then developed: data collection, preprocessing, Fuzzy Inference System generation, and the validation of results. To test this methodology, the analgesia control scenario was analysed. Specifically, the viability of the Analgesia Nociception Index as a guiding variable for the analgesic process during surgical interventions was studied. Real data was obtained from fifteen patients undergoing cholecystectomy surgery. (shrink)

In assisted dying, the end-of-life trajectory is shortened to relieve unbearable suffering. Unbearable suffering is defined broadly enough to include cognitive (early dementia), psychosocial or existential distress. It can include old-age afflictions that are neither life-threatening nor fatal in the “vulnerable elderly”. The voluntary refusal of food and fluids (VRFF) combined with continuous deep sedation (CDS) for assisted dying is legal. Scientific understanding of awareness of internal and external nociceptive stimuli under CDS is rudimentary. CDS may blunt the wakefulness component (...) of human consciousness without eradicating internal affective awareness of thirst and hunger. Patients may suffer because of the slow dying process following dehydration and starvation. The difficulty to adequately control distress, without bringing the dying process to a rapid conclusion by lethal pharmacological interventions, can cause feelings of guilt among hospice and medical staff. Furthermore, the double-effect principle is not applicable in these situations because the primary objective of VRFF is to hasten death. Legal and societal debate should focus on sharpening the boundaries between assisted dying and palliative care. This separation is necessary to: 1) uphold trust in the patient-phyician relationship, and 2) preserve integrity and ethics of the medical profession. (shrink)

Are fetuses, at any stage of their development, capable of feeling pain? In his paper, ‘Locating the Beginnings of Pain’, Stuart Derbyshire argues that they are not. We argue that he reaches this conclusion by way of conceptual confusion, a misreading of the available scientific data and the inclusion of irrelevant data. Despite his assertion to the contrary, the work of most scientists in the area supports the conclusion that fetuses can feel pain. At the outset we examine the concept (...) of pain and distinguish it from the allied concept of nociception, with which it is sometimes confused. With the relevant conceptual framework in place, we elucidate the problem of determining when, in its development, a human becomes capable of feeling pain. We then examine the available data showing how, on balance, it tends more to support than undermine the claim that fetuses of around 28 to 30 weeks' gestation are capable of feeling pain. (shrink)

Previous studies examining EEG and LORETA in patients with chronic pain discovered an overactivation of high theta and low beta power in central regions. MEG studies with healthy subjects correlating evoked nociception ratings and source localization described delta and gamma changes according to two music interventions. Using similar music conditions with chronic pain patients, we examined EEG in response to two different music interventions for pain. To study this process in-depth we conducted a mixed-methods case study approach, based on (...) three clinical cases. Effectiveness of personalized music therapy improvisations versus preferred music on chronic pain was examined with 16 participants. Three patients were randomly selected for follow-up EEG sessions three months post-intervention, where they listened to recordings of the music from the interventions provided during the research. To test the difference of EM versus preferred music, recordings were presented in a block design: silence, their own composed EM, preferred music, and a non-participant’s EM as a control. Participants rated their pain before and after the EEG on a 1–10 scale. We conducted a detailed single case analysis to compare all conditions, as well as a group comparison of entrainment-healing condition versus preferred music condition. Power spectrum and according LORETA distributions focused on expected changes in delta, theta, beta, and gamma frequencies, particularly in sensory-motor and central regions. Intentional moment-by-moment attention on the sounds/music rather than on pain and decreased awareness of pain was experienced from one participant. Corresponding EEG analysis showed accompanying power changes in sensory-motor regions and LORETA projection pointed to insula-related changes during entrainment-pain music. LORETA also indicated involvement of visual-spatial, motor, and language/music improvisation processing in response to his personalized EM which may reflect active recollection of creating the EM. Group-wide analysis showed common brain responses to personalized entrainment-healing music in theta and low beta range in right pre- and post-central gyrus. We observed somatosensory changes consistent with processing pain during entrainment-healing music that were not seen during preferred music. These results may depict top–down neural processes associated with active coping for pain. (shrink)

Numerous mediators are involved in both the control and the transmission of nociceptive messages, and several lines of research have been developed in the management of pain. Complete enkephalin- degrading enzyme inhibitors, which produce naloxone-reversible analgesia in all tests where morphine has been found to be active, remains the most promising way. CCK compounds, especially the CCKB antagonists also may be interesting drugs. Indeed, they are able to strongly potentiate the antinociceptive effects of the opioids. [dickenson, wiesenfeld-hallin et al.].

Fibromyalgia is a chronic pain syndrome characterized by dysfunctional processing of nociceptive stimulation. Neuroimaging studies have pointed out that pain-related network functioning seems to be altered in these patients. It is thought that this clinical symptomatology may be maintained or even strengthened because of an enhanced expectancy for painful stimuli or its forthcoming appearance. However, neural electrophysiological correlates associated with such attentional mechanisms have been scarcely explored. In the current study, expectancy processes of upcoming laser stimulation (painful and non-painful) and (...) its further processing were explored by event-related potentials (ERPs). Nineteen fibromyalgia patients and twenty healthy control volunteers took part in the experiment. Behavioral measures (reaction times and subjective pain perception) were also collected. We manipulated the pain/no pain expectancy through an S1–S2 paradigm (cue-target). S1 (image: triangle or square) predicted the S2 appearance (laser stimulation: warmth or pinprick sensation). Laser stimuli were delivered using a CO2 laser device. Temporal and spatial principal component analyses were employed to define and quantify the ERP component reliability. Statistical analyses revealed the existence of an abnormal pattern of pain expectancy in patients with fibromyalgia. Specifically, our results showed attenuated amplitudes at posterior lCNV component in anticipation of painful stimulation that was not found in healthy participants. In contrast, although larger P2 amplitudes to painful compared to innocuous events were shown, patients did not show any amplitude change in this laser-evoked response as a function of pain predictive cues (as occurred in the healthy control group). Additionally, analyses of the subjective perception of pain and reaction time indicated that laser stimuli preceded by pain cues were rated as more painful than those signaling non-pain expectancy and were associated with faster responses. Differences between groups were not found. The present findings suggest the presence of dysfunction in pain expectation mechanisms in fibromyalgia that eventually may make it difficult for patients to correctly interpret signs that prevent pain symptoms. Furthermore, the abnormal pattern in pain expectancy displayed by fibromyalgia patients could result in ineffective pain coping strategies. Understanding the neural correlates of pain processing and its modulatory factors is crucial to identify treatments for chronic pain syndromes. (shrink)

While seeking novel food sources to feed the increasing population of the globe, several alternatives have been discussed, including algae, fungi or in vitro meat. The increasingly propagated usage of farmed insects for human nutrition raises issues regarding food safety, consumer information and animal protection. In line with law, insects like any other animals must not be reared or manipulated in a way that inflicts unnecessary pain, distress or harm on them. Currently, there is a great need for research in (...) the area of insect welfare, especially regarding species-specific needs, health, farming systems and humane methods of killing. Recent results from neurophysiological, neuroanatomical and behavioral sciences prompt caution when denying consciousness and therefore the likelihood of presence of pain and suffering or something closely related to it to insects. From an animal protection point of view, these issues should be satisfyingly solved before propagating and establishing intensive husbandry systems for insects as a new type of mini-livestock factory farming. (shrink)

This work focuses on the application of machine learning techniques to assist the clinicians in the administration of analgesic drug during general anaesthesia. Specifically, the main objective is to propose the basis of an intelligent system capable of making decisions to guide the opioid dose changes based on a new nociception monitor, the analgesia nociception index. Clinical data were obtained from 15 patients undergoing cholecystectomy surgery. By means of an off-line study, machine learning techniques were applied to analyse (...) the possible relationship between the analgesic dose changes performed by the physician due to the hemodynamic activity of the patients and the evolution of the ANI. After training different classifiers and testing the results under cross validation, a preliminary relationship between the evolution of ANI and the dosage of remifentanil was found. These results evidence the potential of the ANI as a promising index to guide the infusion of analgesia. (shrink)

In patients with pain characterized by a painful focus and allodynia, the painful symptoms arise from altered central processing that is initiated and subsequently maintained by persistent input from nociceptive afferents. Treatments directed at this normal consequence of persistent input are inherently limited. The most efficacious treatments will target the pathology, the various sources of ongoing nociceptor input. [blumberg et al.; coderre & katz; dickenson].

There is a large amount of evidence of placebo and nocebo effects showing that one’s expectation of a forthcoming pain can influence the subsequent experience of pain. Here I shall not discuss the implications of these findings for the nature of pain, but focus instead on the nature of pain anticipation itself. This notion indeed remains poorly analysed and it is unclear what type of anticipatory state it involves. I shall argue that there is more to pain anticipation than a (...) mere combination of anticipatory beliefs and fears. When the impending damage is imminent, pain anticipation involves a distinctive sui generis mental state, which I call nociceptive prediction. One then anticipates the forthcoming event under the pain mode. After analysing its points of similarities and differences with pain, I shall argue that nociceptive prediction is best understood in imperative defensive terms. (shrink)

Pains that persist long after damaged tissue hasrecovered remain a perplexing phenomenon. Theseso-called chronic pains serve no useful function foran organism and, given its disabling effects, mighteven be considered maladaptive. However, a remarkablesimilarity exists between the neural bases thatunderlie the hallmark symptoms of chronic pain andthose that subserve learning and memory. Bothphenomena, wind-up in the pain literature andlong-term potentiation (LTP) in the learning andmemory literature, are forms of neuroplasticity inwhich increased neural activity leads to a longlasting increase in the excitability (...) of neuronsthrough structural modifications at pre- andpost-synaptic sites. Moreover, the synapticmodifications of wind-up and LTP share a commonmechanism: a glutamate N -methyl-D-aspartate(NMDA) receptor interaction that initiates a calciummediated biochemical cascade that ultimately enhancessignal processing at the -amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptor. This paper arguesthat chronic pain, which has no adaptive value, canbe accounted for in terms of the highly adaptivephenomenon of activity-dependent neural plasticity;hence, some cases of chronic pain can beconceptualized as a memory trace in spinal neurons. (shrink)

I argue that pain sensations are perceptual states, namely states that represent (actual or potential) damage. I defend this position against the objection that pains, unlike standard perceptual states, do not allow for an appearance-reality distinction by arguing that in the case of pain as well as in standard perceptual experiences, cognitive penetration or malfunctions of the underlying sensory systems can lead to a dissociation between the sensation on the one hand, and what is represented on the other hand. Moreover, (...) I refute the objection that the allegedly weak correlation between pain and bodily damage forces intentionalist accounts of pain to postulate so many malfunctions (misrepresentations respectively) that such accounts become implausible. I also rebut Murat Aydede’s objection that our linguistic practice supposedly shows that there is a conceptual difference between standard perceptual experiences and pain sensations by challenging Aydede’s premise that we always withdraw standard perceptual reports in case of counterevidence, while we never do that with pain reports. At the end, I propose an explanation as to why we do not express perceptual reports of (potential) bodily damage in objectivist, but in mental terms. (shrink)

Evidence that central sensitization needs to be maintained in an ongoing manner by nociceptive input from the periphery makes the peripheral drive, rather than the central amplification process, the highest priority target for understanding and control. To stop the peripheral drives to kill two birds with one stone. Moreover, the amplification that central sensitization does provide is selective and not necessarily striking in intensity. A that neutralized central sensitization would probably be less effective in controlling persistent pain than many investigators (...) would like to believe. [berkley; blumberg et al.; coderre & katz; dickenson; mcmahon; weisenfeld-hallin et al.]. (shrink)

This target article examines the clinical and experimental evidence for a role of peripheral and central hyperexcitability in persistent pain in four key areas: cutaneous hyperalgesia, referred pain, neuropathic pain, and postoperative pain. Each suggests that persistent pain depends not only on central sensitization, but also on inputs from damaged peripheral tissue. It is instructive to think of central sensitization as comprised of both an initial central sensitization and an ongoing central sensitization driven by inputs from peripheral sources. Each of (...) these factors, initial sensitization, ongoing central sensitization, and inputs from peripheral sources, contributes to the net activity in dorsal horn neurons and thus influences the expression of persistent pain or hyperalgesia. Since each factor, peripheral inputs and central sensitization (initial or ongoing), can contribute to both the initiation and maintenance of persistent pain, therapies should target both peripheral and central sources of pathology. (shrink)

The spinal mechanisms of action of opioids under normal conditions are reasonably well understood. The spinal effects of opioids can be enhanced or reduced depending on pathology and activity in other segmental and nonsegmental pathways. This plasticity will be considered in relation to the control of different pain states using opioids. The complex and contradictory findings on the supraspinal actions of opioids are explicable in terms of heterogeneous descending pathways to different spinal targets using multiple transmitters and receptors – therefore (...) opioids can both increase and decrease activity in descending pathways. These pathways could exhibit considerable plasticity. There is increasing evidence that delta opioid receptor agonists have the potential to replace morphine as major analgesics with reduced side-effect profiles. The concept of preemptive analgesia, based on preventing the induction of some of the negative plastic influences on opioid controls and the detrimental effects of pain, is sound, but experimental verification in the clinical setting is difficult. For example, a delayed compensatory upregulation of inhibitory systems, particularly in inflammation, may counter persistent painful inputs. Combination therapy with opioids may be beneficial in many pain states where either negative influences are blocked or inhibitory controls are enhanced. Finally, developmental aspects of these systems are discussed in connection with the treatment of pain in young children, where inhibitory systems in the spinal cord are immature. (shrink)