Pain is not a single entity but is instead a collection of sensory experiences commonly associated with tissue damage. There is growing recognition that not all pains are equivalent, that pains and pathologies are not related in a simple manner, and that acute pains differ in many respects from persistent pains. Great strides have been made in improving our understanding of the neuronal mechanisms responsible for acute pain, but the studies leading to these advances have also led to the realization that a bewildering array of processes are interposed between tissue damage and sensations of pain, especially in persistent pains. Persistent pains often seem unrelated or disproportionate to identifiable pathology, and they are modulated by a multitude of factors. This complexity in such a vital function serves as a challenge both to scientists seeking fundamental understanding and to clinicians faced with the immediate need to treat patients with painful disorders.

Let's start from scratch in thinking about what memory is for, and consequently, how it works. Suppose that memory and conceptualization work in the service of perception and action. In this case, conceptualization is the encoding of patterns of possible physical interaction with a three-dimensional world. These patterns are constrained by the structure of the environment, the structure of our bodies, and memory. Thus, how we perceive and conceive of the environment is determined by the types of bodies we have. Such a memory would not have associations. Instead, how concepts become related (and what it means to be related) is determined by how separate patterns of actions can be combined given the constraints of our bodies. I call this combination “mesh.” To avoid hallucination, conceptualization would normally be driven by the environment, and patterns of action from memory would play a supporting, but automatic, role. A significant human skill is learning to suppress the overriding contribution of the environment to conceptualization, thereby allowing memory to guide conceptualization. The effort used in suppressing input from the environment pays off by allowing prediction, recollective memory, and language comprehension. I review theoretical work in cognitive science and empirical work in memory and language comprehension that suggest that it may be possible to investigate connections between topics as disparate as infantile amnesia and mental-model theory.

In this target article the following hypotheses are discussed: (1) Colour is autonomous: a perceptuolinguistic and behavioural universal. (2) It is completely described by three independent attributes: hue, brightness, and saturation: (3) Phenomenologically and psychophysically there are four unique hues: red, green, blue, and yellow; (4) The unique hues are underpinned by two opponent psychophysical and/or neuronal channels: red/green, blue/yellow. The relevant literature is reviewed. We conclude: (i) Psychophysics and neurophysiology fail to set nontrivial constraints on colour categorization. (ii) Linguistic evidence provides no grounds for the universality of basic colour categories. (iii) Neither the opponent hues red/green, blue/yellow nor hue, brightness, and saturation are intrinsic to a universal concept of colour. (iv) Colour is not autonomous.

How do minds emerge from developing brains? According to “neural constructivism,” the representational features of cortex are built from the dynamic interaction between neural growth mechanisms and environmentally derived neural activity. Contrary to popular selectionist models that emphasize regressive mechanisms, the neurobiological evidence suggests that this growth is a progressive increase in the representational properties of cortex. The interaction between the environment and neural growth results in a flexible type of learning: “constructive learning” minimizes the need for prespecification in accordance with recent neurobiological evidence that the developing cerebral cortex is largely free of domain-specific structure. Instead, the representational properties of cortex are built by the nature of the problem domain confronting it. This uniquely powerful and general learning strategy undermines the central assumption of classical learnability theory, that the learning properties of a system can be deduced from a fixed computational architecture. Neural constructivism suggests that the evolutionary emergence of neocortex in mammals is a progression toward more flexible representational structures, in contrast to the popular view of cortical evolution as an increase in innate, specialized circuits. Human cortical postnatal development is also more extensive and protracted than generally supposed, suggesting that cortex has evolved so as to maximize the capacity of environmental structure to shape its structure and function through constructive learning.

A functional theory of memory has already been developed as part of a general functional theory of cognition. The traditional conception of memory as “reproductive” touches on only a minor function. The primary function of memory is in constructing values for goal-directedness of everyday thought and action. This functional approach to memory rests on a solid empirical foundation.

No crucial experiment demonstrates that four hue categories are needed to describe color appearance. Instead, converging lines of evidence suggest that the terms red, yellow, green, and blue are sufficient and precise enough for deriving color discrimination functions and for a useful model constraining relations between color appearance and neuronal responses. Such a model need not be based on linguistic universals. Until something better is available, this “standard model” holds.

Although the developmental arguments in the Quartz & Sejnowski (Q&S) target article may have intrinsic merit, they do not warrant the authors' conclusion that innate modular architectures are absent or minimal, and that neocortical evolution is simply a progression toward more flexible representational structures. Modular architectures can develop and evolve in tandem with sub-cortical specialisation. I present comparative evidence for the co-evolution of specific thalamic and cortical visual pathways.

Are there sex differences in pain? For experimentally delivered somatic stimuli, females have lower thresholds, greater ability to discriminate, higher pain ratings, and less tolerance of noxious stimuli than males. These differences, however, are small, exist only for certain forms of stimulation and are affected by many situational variables such as presence of disease, experimental setting, and even nutritive status. For endogenous pains, women report more multiple pains in more body regions than men. With no obvious underlying rationale, some painful diseases are more prevalent among females, others among males and, for many diseases, symptoms differ between females and males. Sex differences in attitudes exist that affect not only reporting, coping, and responses to treatment, but also measurement and treatment. So many variables are operative, however, that the most striking feature of sex differences in reported pain experience is the apparent overall lack of them. On the other hand, deduction from known biological sex differences suggests that these are powerful sex differences in the operation of pain mechanisms. First, the vaginal canal provides an additional route in women for internal trauma and invasion by pathological agents that puts them at greater risk for developing hyperalgesia in multiple body regions. Second, sex differences in temporal patterns are likely to give rise to sex differences in how pain is “learned” and stimuli are interpreted, a situation that could lead to a greater variability and wider range of pains without obvious peripheral pathology among females. Third, sex differences in the actions of sex hormones suggest pain-relevant differences in the operation of many neuroactive agents, opiate and nonopiate systems, nerve growth factor, and the sympathetic system. Thus, while inductive analysis of existing data demonstrate more similarities than differences in pain experience between females and males, deductive analysis suggests important operational sex differences in its production.

The physics of color and the psychology of color naming are not isomorphic. Physically, the spectrum is continuous with regard to wavelength – one point in the spectrum differs from another only by the amount of wavelength difference. Psychologically, hue is categorical – colors change qualitatively from one wavelength region to another. The psychological characterization of hue that characterizes color vision has been revealed in a series of modern psychophysical studies with human adults and infants and with various infrahuman species, including vertebrates and invertebrates. These biopsychological data supplant an older psycholinguistic and anthropological literature that posited that language and culture alone influence perceptual processes; language and culture may modify color naming beyond basic categorizations.

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.

Glenberg's theory is rich and provocative, in our view, but we find fault with the premise that all memory representations are embodied. We cite instances in which that premise mispredicts empirical results or underestimates human capabilities, and we suggest that the motivation for the embodiment idea – to avoid the symbol-grounding problem – should not, ultimately, constrain psychological theorizing.

Constructivism is the most recent in a long line of failed attempts to discredit nativism. It seeks support from true (but irrelevant) facts, wastes its energy on straw men, and jumps logical gaps; but its greatest weakness lies in its failure to match nativism's explanation of a wide range of disparate phenomena, particularly in language acquisition.

Glenberg's rethinking of memory theory seems limited in its ability to handle abstract symbolic thought, the selective character of cognition, and the self. Glenberg's framework can be elaborated by linking it with theoretical efforts concerned with cognitive development (Piaget) and ecological perception (Gibson). These elaborations point to the role of memory in specifying the self as an active agent.

We argue that the confusing pattern of evidence concerning colour categorization reported by Saunders & van Brakel is unsurprising. On a perspectival view, categorization may follow semantic or pragmatic attributes. Colour lacks clear semantic attributes; as a result categorization is necessarily pragmatic and context-sensitive. This view of colour categorization helps explain the developmental delay in colour naming.

Much of our work with enriched experience and training in animals supports the Quartz & Sejnowski (Q&S) thesis that environmental information can interact with pre-existing neural structures to produce new synapses and neural structure. However, substantial data as well as an evolutionary perspective indicate that multiple information-capture systems exist: some are constructivist, some are selectionist, and some may be tightly constrained.

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.

The present commentary addresses the Quartz & Sejnowski (Q&S) target article from the point of view of the dynamical learning algorithm for neural networks. These techniques implicitly adopt Q&S's neural constructivist paradigm. Their approach hence receives support from the biological and psychological evidence. Limitations of constructive learning for neural networks are discussed with an emphasis on grammar learning.

This commentary expresses basic agreement with Saunders & van Brakel, gives explanations for some of the frailties they see in color science, and suggests that the conditioning forces of modern technology may render color categories increasingly useful even if not initially “real.”

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.

We are sympathetic to most of what Glenberg says in his target article, but we consider it common wisdom rather than something radically new. Others have argued persuasively against the idea of abstraction in cognition, for example. On the other hand, Hebbian connectionism cannot get along without the idea of association, at least at the neural level.