Pain and the primate thalamus.
Noxious stimuli that are perceived as painful, are conveyed to the thalamus by the spinothalamic tract (STT) and the spinotrigeminothalamic tracts (vSTT), arising from the dorsal horn of the spinal cord and medulla, respectively. Most investigators have concluded that the thalamic terminus of these pathways include several nuclei of the somatosensory and intralaminar thalamus. Non-noxious stimuli are carried by the dorsal column/medial lemniscal or the trigeminothalamic pathways which terminate in much more restricted regions of the thalamus than do the STT and vSTT systems. Lesions of components of the somatosensory pathways result in profound changes in the circuitry of the recipient thalamic nuclei. Not only are there the expected losses of the injured axons and their synaptic terminations, but there is also a marked reduction of the intrinsic GABAergic circuitry, even though the GABAergic neurons contributing to the circuitry have not been injured directly by lesions of the afferent pathways. Such changes in the inhibitory circuitry observed in experimental animals may explain the abnormal bursting behavior of thalamic neurons found in patients with central deafferentation pain syndromes. One potential approach to treating chronic pain would be to selectively remove the neurons of the superficial dorsal horn (lamina I) that specifically respond to noxious stimuli (NS neurons). A toxin has been developed (SSP saporin) that binds to the substance P receptor of NS neurons, is internalized by the neuron and kills the cell. SSP saporin has been shown to be effective in rats, and we have recently demonstrated that it effectively causes lesions in NS neurons of the lumbar spinal cord in the monkey and reduces the animals' response to noxious cutaneous stimuli. The SSP-saporin administration to the lumbar spinal cord destroys a relatively small number of the total neurons that project into the somatosensory thalamus and does not lead to demonstrable changes in the inhibitory circuitry of the thalamus, in contrast to lesions of major pathways that lead to reductions in the thalamic inhibitory circuitry.
Ralston
Henry J
HJ
Department of Anatomy, W. M. Keck Foundation Center for Integrative Neuroscience, University of California, San Francisco, CA 94143-0452, USA. hjr@phy.ucsf.edu
D000818:Animals; D006801:Humans; D007395:Interneurons / Q000378:metabolism / Q000473:pathology; D009433:Neural Inhibition / Q000502:physiology; D009619:Nociceptors / Q000378:metabolism / Q000473:pathology; D010146:Pain / Q000378:metabolism / Q000503:physiopathology*; D059408:Pain Management; D020671:Posterior Horn Cells / Q000503:physiopathology / Q000601:surgery; D011323:Primates / Q000033:anatomy & histology* / Q000502:physiology; D013133:Spinothalamic Tracts / Q000503:physiopathology*; D013788:Thalamus / Q000033:anatomy & histology / Q000503:physiopathology*; D014279:Trigeminal Nucleus, Spinal / Q000503:physiopathology*