The underlying theme in all the NAB projects was the dynamic activity-dependent plasticity of the nervous system. "Pain" emerged from these studies not as a simple sensory perception, but a complex set of responses to environmental situations.

Dubner's studies of the plastic and interactive neural connections underlying the responses of awake behaving monkeys to sensory stimuli, and the work of Dionne ,Gracely ,Max , and Bennett in discriminating the sensory and affective responses of awake behaving humans to acute and chronic pain, and relating these to neurochemical and neurophysiological mechanisms, were paralleled by continuing neuroanatomical work by Steve Gobel , and, after 1976, M. A. Ruda [with Jan Hylden and Haruhide Hayashi ].

Gobel's studies with the electron microscope traced the axons and dendrites of the trigeminal system and the spinal cord, identifying those neurons which projected to the brain, and mapping the network of local "interneurons" within the spinal cord. Some of these were "excitatory" interneurons, which appeared to act as synaptic relay stations, between the nerves sending information from the skin and internal organs, and the neurons carrying information to the brain. Others acted as inhibitors by creating neural 'dead ends', dampening or blocking the synaptic information.

In the late 1970s, Ruda used several newly developed methods to label and trace synaptic pathways. These included "tagging" cellular compounds with flourescent antibodies or with the enzyme horseradish peroxidase, or using nucleic acid probes which bind to cellular DNA. With these techniques, she was able to follow the activity of the newly discovered "chemical messengers" of the nervous system, the neurotransmitters and neuropeptides. By the mid-80s, a number of these mediators had been found to be active in the nervous system's response to pain.

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