A pain in the thalamus.

The review of Willis et al is one that clearly needed to be written. It raises two important issues, one of them perennial, the other current if probably ephemeral. The first stems from the idea that the pathway running from lamina I of the dorsal horn of the spinal cord can be regarded as “the” painand thermospecific pathway and that it relays in regions of the thalamus outside the classic somatosensory relay nuclei, en route to areas of cerebral cortex in the insular and cingulate regions. The second deals with the exact localization of the part of the thalamus identified by Craig and coworkers as the relevant relay center. The idea that all aspects of the phenomenon we know as pain can be explained on the basis of a single hardwired line of connections running from the small nerve fibers of peripheral nerves, through lamina I of the dorsal horn, and terminating outside the primary somatosensory areas of the cortex is by no means novel, but it has received considerable currency and, as PD Wall pointed out some years ago in the pages of this journal, if correct it would be a God-send to patients seeking relief from intractable chronic pain. In reading the article by Willis et al, one cannot fail to be struck by the large body of evidence that exists for the involvement of the primary somatosensory relay nucleus (ventral posterior medial [VPM] and ventral posterior lateral [VPL]) of the thalamus and its cortical projection in the postcentral gyrus in the discrimination of pain intensity and localization. It would be surprising if the detailed fine grain topographic maps of the body surface that exist in the primary somatosensory areas were excluded from the discriminative apparatus underlying pain localization in favor of the insula in which topographic maps and modality segregation are not the norm. I think the view that any part of the thalamus that excludes the ventral posterior nucleus and the primary somatosensory areas of the cortex in the pathways leading to pain perception cannot be sustained in the face of the broad range of data presented here by Willis et al. Even if one accepts, which as pointed out by Wall earlier many do not, the belief that lamina I cells can provide all the information necessary for the appreciation of pain and temperature, the evidence that they project exclusively to targets outside the VPM and VPL nuclei and/or that these targets are only innervated by layer I cells is weak at best. Craig et al in their initial article described labeled axons in a region they called VMpo and located outside the confines of VPL and VPM after injections of anatomic tracers putatively restricted to layer I of the dorsal horn. The restriction of an injection to lamina I is a remarkable technical feat, given the small dimensions of lamina I, and even if true, any injection restricted to lamina I inevitably has to be very tiny and cannot possibly label a sufficient number of cells to permit projections to other sites to be ruled out. The studies involving retrograde labeling of layer I cells after injections of tracers in the thalamus itself clearly show labeling of lamina I cells after injections well outside the supposed pain relay center, proving the existence of a lamina I projection there, as the results of a large number of physiologic studies bear out. Injections of retrograde tracers targeted at the new thalamic pain center did not selectively involve it. Also there are no data that rule out the projection of deeper spinothalamic cells to it. Trying to identify the region referred to as VMpo presents difficulties, as Willis et al point out. These difficulties to some extent arise from the relative paucity of studies now being conducted on thalamic anatomy. With much of the emphasis in modern studies of the thalamus having gone off anatomy and connection tracing in favor of investigating the physiologic properties of thalamic neurons and the network of which they form a part, the demand for reproducibility of anatomic results often takes longer to be met than in a previous era. Anyone can now more or less draw a line around any part of the thalamus and call it something that reflects a particular point of view without much concern for antecedent work or the expectation that new studies may soon prove it to be an oversimplification. The problem with “VMpo” is that it has never been adequately described and, where illustrated, it has usually been either as a small blob of immunoreactivity against a blank background or in an isolated section or two matched to others in which the Nissl staining is washed out and of little localizing value. If the preexisting literature was considered at all, it was only dismissively. The preexisting literature presents a rather different picture of the nuclear delineations of the posterior part of the primate thalamus on the basis of a far more comprehensive study of immunostaining for the calcium binding proteins. The basic difference between his analysis and that of the earlier studies, according to Craig (and restated in the Willis et al article), is that the antibodies against 28-kd calbindin used in the two sets of studies label different things—the commercial Sigma monoclonal antibody used by Craig only fibers, and the polyclonal antiserum used by us only cells. Given that they are directed against identical epitopes, this would be a remarkable differential specificity, if only it were true. Our studies had in fact emphasized staining of fiFrom the Center for Neuroscience, University of California, Davis, CA. Address reprint requests to Dr. Edward Jones, University of California, Davis, Center for Neuroscience, 1544 Newton Court, Davis, CA 95615. © 2002 by the American Pain Society 1526-5900/2002 $35.00/0 doi:10.1054/jpai.2002.122952