Physiology of Lamina I and V STT Cells

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The spinothalamic tract (STT) is an important ascending pathway for activity associated with pain, temperature and itch sensations in primates and humans. Prior studies in this laboratory indicate that modality- selective lamina I STT neurons that project in the lateral STT have a integral role in these sensations. Studies in other laboratories, hoever, report that the responses of 'wide dynamic range' (WDR) STT neurons in lamina V, which ascend in the anterior STT, correlate with pain sensation and with hyperalgesia. Indeed, neurons in both populations are activated by stimulate that evoke pain, temperature, and itch sensations, yet both comprise several subclasses of cells that are activated by particular stimuli. This project is based on the global hypothesis that subclasses of lamina I and lamina V STT neurons carry complementary information to the forebrain that must be integrated to produce the several aspects of these sensations This hypothesis is consistent with clinical data suggesting that multiple ascending pathways are involved in pain, and with imaging observations showing that multiple forebrain regions are activated during these sensations. Knowledge of the activity in different subclasses of laminae I and V STT neurons that project to different targets in the primate thalamus is inadequate, despite considerable prior work. For example, polymodal nociceptive (HPC) lamina I STT cells that project to Vmpo have never been characterized, and the role of lamina V STT cells that project to VPL in the thermal grill illusion of pain has never been examined. In order to test specific hypothesis that anticipate which subclasses of laminae I aNd V STT cells display responses corresponding to different sensations, we will functionally characterize single laminae I and V STT neurons using five noel quantitative stimulus paradigms that distinguish different aspects of these sensations: (Aim 1) repeated brief contact heat [,second pain']; (Aim 2) graded tonic pressure ['first pain']; (Aim 3) iontophoretic histamine [itch]; (Aim 4) the algogens capsaicin and mustard oil (burning pain and hyperalgesia]; and (Aim 5) the thermal grill [illusory cold pain]. Using protocols that hae been refined in experiments in cats (which have almost no WDR lamina I STT cells and comparatively few lamina V STT cells), the goal of these experiments will be to obtain data in macaque monkeys that can be directly compared (across primates) with published human psychophysical evidence obtained using the same stimulus paradigms. Preliminary findings verify the feasibility of these experiments and validate the discriminative value of these paradigms. This research will provide new insights into the synergy between lamina I and V STT neurons and into the integration underlying pain, temperature and itch sensations that is altered in clinical disorders.