The evidence favoring sex differences in pain seems compelling (berkley). This commentary considers the role of such factors as anxiety, somatosensory amplification, and coping style in accounting for the differential response to pain in the laboratory and clinic, and emphasizes the need to base evaluation and treatment upon individual reports rather than gender-based stereotypes.

Evolution is not like an exam in which pre-set problems need to be solved. Failing to recognise this point, Clark & Thornton misconstrue the type of explanation called for in species learning although, clearly, species that can trade spaces have more chances to discover novel beneficial behaviours. On the other hand, the trading spaces strategy might help to explain lifetime learning successes.

We discuss anatomical data that may represent the substrate for very diverse input to a single folium, indirectly supporting the notion of a laterolateral beam spreading along the long axis of a folium. We also raise the question of whether the more linear body representation in somatosensory cortico-ponto-cerebellar pathways represent an adaptation to sequential processing of information from contiguous body parts.

Examples of how LTP and LTD can control adaptively-timed learning that modulates attention and motor control are given. It is also suggested that LTP/LTD can play a role in storing memories. The distinction between match-based and mismatch-based learning may help to clarify the difference.

LTP is thought to be an experimental model for studying the cellular mechanism of learning and memory. Shors & Matzel review some contradictory data concerning the linkage between LTP and memory and suggest that LTP does not underlie learning and memory. LTP is a cellular and synaptic process and cannot be a memory mechanism. In fact, it is a cellular information storage mechanism.

A fundamental problem with the Clark & Thornton definition of a type-1 problem (requirement 2) is identified. An alternative classical statistical formulation is proposed where a type-1 (learnable) problem corresponds to the case where the learning machine is capable of representing its statistical environment.

The possible dysfunction of γ aminobutyric acid (GABA) and opioid inhibitory mechanisms following central and peripheral nervous system injury is an important and potentially useful finding. However, effective clinical application must take into account the specific characteristics of the models used in the studies and the relationship of these models to specific clinical conditions. [dickenson; wiesenfeld-hallin et al.]

Braitenberg et al.'s proposal, like most previous theories of cerebellar function (see Bower 1997, for review), is fundamentally based on the striking geometric relationship between parallel fibers and Purkinje cells. As in previous models, the current theory assumes that the activation of granule cells results in a “beam” of activated Purkinje cells, although it adds the new requirement that the granule cell layer itself have a particular spatial/temporal pattern of activation. I believe there is clear evidence that parallel fibers do not have the type of excitatory effects on Purkinje cells required by this theory.

The hypothesis that there is a 1:1 correspondence between LTP and learning is simplistic, and the correlation approach to testing it is therefore too limited. The alternative hypothesis that LTP plays a role in arousal is consistent with activity-dependent neuromodulation, but ignores the Hebbian properties of LTP. LTP may involve both types of mechanisms, suggesting a possible synthesis of the two hypotheses.

dickenson briefly mentions that peripheral opioid receptors somehow become active following inflammation and that the appearance of endogenous opioid peptides at the injury site may be related to immune cell proliferation. Recent findings elucidate the underlying mechanisms in more detail and provide an incentive for the development of a novel generation of analgesics devoid of typical central opioid side effects.

Braitenberg et al.'s target article presents the best current integration of anatomical and physiological data, and provides a qualitative description of cerebellar function in terms of the dynamics of processes based on the geometry of the cerebellar cortex. We compare the proposed model to our own quantitative model based on the concept of Purkinje unit.

Clark & Thornton (C&T) have demonstrated the paradox between the opacity of the transformations that underlie relational mappings and the ease with which people learn such mappings. However, C&T's trading-spaces proposal resolves the paradox only in the broadest outline. The general-purpose algorithm promised by C&T remains to be developed. The strategy of doing so is to analyze and formulate computational mechanisms for known cases of recoding.

The distinction between uninformed learning (type-1) and learning based on recoding using prior information (type-2) helps to clarify some long-standing psychological problems, including misunderstanding of mathematics by children, the need for active construction of concepts in cognitive development, and the difficulty of configural learning tasks. However, an alternative to recoding some type-2 tasks is to represent the input as separate dimensions, which are processed jointly. This preserves the original structure, but is subject to processing capacity limitations.

This commentary addresses the strength of the comparative approach to the study of sex differences in pain. Animal studies can focus our attention on mechanisms of sex differences in these clinical sex differences. Important sex differences are seen in descending pain modulation, thereby providing an explanation for the observation of sex differences in pain perception. [berkley]

Braitenberg et al.'s view that the cerebellum contributes “mechanical efficiency” to multijoint sequences of movement is too narrow to account adequately for results from new anatomical, neurobehavioral, and neuroimaging studies. A broader view is that the cerebellum modulates attention, sensory, motor, and other neural systems in order to accomplish its prime function, which is to learn to predict and prepare for imminent information acquisition, analysis, or action.

The problem of neural memory storage is discussed, based on the results of studies of memory impairment after hippocampal lesions, motor learning, and electrophysiological research on “spinal memory.” I support Shors & Matzel's major statements. The absence of reliable evidence on the LTP memory storage function and other data cast doubt on the synaptic theory of memory.

The main assumptions on which the tidal wave hypothesis rests will be questioned. First, since focal synchronous mossy fibre input is sufficient to ensure spread of activity along the parallel fibres, the tidal wave is redundant. Second, spatial and temporal characteristics of mossy fibre input make spatio-temporal sequences appropriate for setting up a tidal wave unlikely in the behaving animal.

Shors & Matzel provide compelling arguments against a role for hippocampal long-term potentiation (LTP) in mammalian learning and memory. As an alternative, they suggest that LTP is an arousal mechanism. I will argue that this view is not a satisfactory alternative to current conceptions of LTP function.

The computational notion of “trading spaces” is highly relevant to the psychological domain of categorization. The “theory” view of concepts can be interpreted as a recoding view. A design principle for exploiting learned recodings in order to handle the type-2 problem of forming sophisticated concepts is outlined.

berkley's line of reasoning about sex and pain experience suggests a completely different perspective on sex differences in human experimental, clinical, and epidemiological pain research. Although physiological mechanisms may place women at greater risk for pain, women may have found ways to dampen the effect of these mechanisms. Nevertheless, it is a challenge to extrapolate physiological mechanisms in human phenomena from outcomes observed in animal models.