Showing papers by "A.D. (Bud) Craig published in 2000"

Thermosensory activation of insular cortex.

Abstract: Temperature sensation is regarded as a submodality of touch, but evidence suggests involvement of insular cortex rather than parietal somatosensory cortices. Using positron emission tomography (PET), we found contralateral activity correlated with graded cooling stimuli only in the dorsal margin of the middle/posterior insula in humans. This corresponds to the thermoreceptive- and nociceptive-specific lamina I spinothalamocortical pathway in monkeys, and can be considered an enteroceptive area within limbic sensory cortex. Because lesions at this site can produce the post-stroke central pain syndrome, this finding supports the proposal that central pain results from loss of the normal inhibition of pain by cold. Notably, perceived thermal intensity was well correlated with activation in the right (ipsilateral) anterior insular and orbitofrontal cortices.

Cytoarchitectonic and immunohistochemical characterization of a specific pain and temperature relay, the posterior portion of the ventral medial nucleus, in the human thalamus

Abstract: Previous studies in the macaque monkey have identified a thalamic nucleus, the posterior portion of the ventral medial nucleus (VMpo), as a dedicated lamina I spinothalamocortical relay for pain and temperature sensation. The dense plexus of calbindin-immunoreactive fibres that characterizes VMpo in primates enables its homologue to be identified in the human thalamus by immunohistochemical labelling for calbindin. We have now analysed in detail the cytoarchitectonic characteristics of VMpo and its relationship with immunoreactivity for calbindin, substance P and calcitonin gene-related peptide (CGRP) in the human thalamus. The area in the posterolateral thalamus in which dense calbindin-immunoreactive fibre terminations are present coincides nearly completely with a distinct region that contains small to medium-sized cells with round or oval shapes that are aggregated in clusters separated by cell sparse areas. This region, which we identify as VMpo, is located posteromedial to the ventral posterior lateral (VPL) and ventral posterior medial (VPM) nuclei, ventral to the anterior pulvinar and centre median nuclei, lateral to the limitans and parafascicular nuclei and dorsal to the medial geniculate nucleus. Calbindin-immunoreactive fibres enter VMpo from the spinal lemniscus and form large patches of dense terminal-like staining over clusters of VMpo neurons. A few of these clusters also display terminal-like substance P labelling. Small bursts of CGRP staining are intercalated between the calbindin-labelled clusters, but there is little or no overlap between these two markers. CGRP immunoreactivity is also present over small, non-clustered neurons in the calbindin-negative area that separates VMpo from the VPL and VPM nuclei, which we denote as the posterior nucleus (Po). These observations provide a concise description of VMpo in the human thalamus. Further, they suggest that the lamina I spinothalamic tract fibres (represented by calbindin and probably also substance P immunoreactivity) and vagal-solitary-parabrachial afferents (represented by CGRP immunoreactivity) form closely related, but separate, termination fields that can be considered to represent different aspects of enteroceptive information regarding the physiological status of the tissues and organs of the body. The location of VMpo and the adjacent Po fits with clinical descriptions of the thalamic area from which pain, temperature and visceral sensations can be evoked by microstimulation, and where nociceptive and thermoreceptive neurons have been recorded in humans. It also corresponds to the area in which infarcts cause analgesia and thermoanaesthesia and can lead to the paradoxical development of central pain.

Is neuropathic pain caused by the activation of nociceptive-specific neurons due to anatomic sprouting in the dorsal horn?

Abstract: Pain is a protective signal. It warns us of an impending or established injury (nociceptive pain) and tells us that the integrity of our tissues is at risk, which could threaten our survival. Accordingly, like other interoceptive signals from the body, pain evokes a number of behavioral, autonomic, and affective reactions that serve to restore homeostasis. However, not all types of pain are adaptive. Thus, chronic pain may occur after damage or disease affecting the nervous system itself. Such neuropathic pain represents a major problem in clinical medicine because it causes systemic changes and debilitating suffering and because, in contrast to nociceptive pain, it is largely resistant to the methods that are presently available for pain relief. A characteristic of neuropathic pain is hyperesthesia, or abnormal responsiveness to somatic sensory stimulation (Lindblom, 1979; Tasker, 1983). Patients suffering from peripheral neuropathies may experience pain (allodynia) provoked solely by touching the skin or by changes in temperature, stimuli that are normally innocuous. These phenomena have been an enigma to pain clinicians and researchers because pain, touch, and temperature not only have specific sets of peripheral receptors but also engage distinct central nervous pathways and are represented in different cortical networks (Coghill et al., 1994; Craig et al., 2000). The occurrence of allodynia implies that, under pathologic conditions, innocuous stimuli in some way gain access to the nociceptive system. In an inspired behavioral and anatomic study, reported on pages 45–61 of this issue of The Journal of Comparative Neurology, Bester et al. provide evidence that this rerouting of innocuous information can be observed in the spinal dorsal horn. They used an animal model for peripheral neuropathies, a crush injury of the sciatic nerve, which is the major nerve providing the sensory and motor innervation of the lower hindlimb and foot. The nerve crush interrupts conduction of activity and leads to peripheral Wallerian degeneration of many sciatic axons, rendering the hindlimb and paw initially denervated. However, because the peripheral Schwann cells and epineurial sheaths are still intact, regeneration will normally occur. Using behavioral testing, Bester et al. observed, like others before them, that, during the return of sensibility, the previously denervated skin becomes hyperesthetic to both mechanical and thermal stimuli, and they found that, when the hypersensitivity was most pronounced, avoidance behaviors were elicited by innocuous brushing of the skin, indicating the presence of allodynia. When Bester et al. examined the spinal cord of these animals, they found that the innocuous stimulation had evoked c-fos, an immediate early gene product expressed after neuronal activation, in neurons in the superficial dorsal horn. Expression of c-fos in these neurons is normally elicited only by noxious stimulation (Hunt et al., 1987) and not by innocuous stimuli. Indeed, in the study by Bester et al., no c-fos was seen in intact rats after brushing the skin or in rats in which the skin on the contralateral, intact side had been stimulated. Moreover, Bester et al. also examined higher centers for c-fos expression and found that brushing of the reinnervated hindlimb similarly activated neurons in the parabrachial nucleus, the major supraspinal termination site in the rat for nociceptive-specific superficial dorsal horn neurons (Hylden et al., 1986; Bester et al., 2000). Thus, the study by Bester et al. shows that, in an animal model of neuropathic pain, innocuous stimuli excite neurons in the superficial dorsal horn and the parabrachial nucleus that are normally activated by noxious nociceptive