Transneuronal tracing of a nociceptive pathway, the spino-(trigemino)-parabrachio-amygdaloid pathway, was performed using an ␣-herpes virus, the Bartha strain of pseudorabies virus (PRV). Microinjection of PRV into the central nucleus of the amygdala (Ce) resulted in progressive retrograde and transneuronal infection of a multisynaptic circuit involving neurons in the brainstem and spinal cord as detected immunocytochemically. At short survival (26 hr), retrogradely labeled neurons were concentrated in the external lateral nucleus of the parabrachial complex (elPB) but were absent from both the trigeminal nucleus caudalis (TNC) and the spinal cord. At longer survivals (52 hr), labeled cells were present in lamina I of both the TNC and spinal dorsal horn. Retrograde labeling from the Ce with Fluorogold demonstrated that elPB neurons have long dendrites extending laterally into the terminal field of spinal and trigeminal afferents, where transneuronal passage of PRV to these afferents could occur. Even longer survivals (76 hr) resulted in a columnar pattern of cell labeling in the TNC and spinal dorsal horn that extended from lamina I into lamina II. At this longest survival, primary sensory neurons became infected. Bilateral excitotoxic lesions of the elPB blocked almost all viral passage from the Ce to superficial laminae of the TNC and spinal dorsal horn. These results demonstrate that nociceptive input to the amygdala is relayed from neurons in lamina I through the elPB. We propose that this modular arrangement of lamina I and II neurons may provide the basis for spinal processing of peripheral input to the amygdala.
Key words: pain pathways; amygdala; superficial dorsal horn; parabrachial nucleus; spinal processing; viral tracer; PRV; pseudorabies virusThe central nucleus of the amygdala (Ce) is the terminal area of a major ascending nociceptive pathway, the spino-(trigemino)-parabrachio-amygdaloid tract . Most Ce neurons respond to noxious, but not innocuous, stimuli (Bernard and Besson, 1990;. The main source of afferents to the Ce is the external lateral parabrachial nucleus (elPB) (Saper, 1995). Previous anatomical studies have, however, failed to demonstrate a significant projection from the spinal dorsal horns and trigeminal nucleus caudalis (TNC) to the elPB (Blomqvist et al., 1989). Rather, afferents from nociceptive regions of the dorsal horn, laminae I and V, terminate in nuclei located in the lateral parabrachial area surrounding the elPB, none of which project to the amygdala (Bernard et al., 1995;Feil and Herbert, 1995;Saper, 1995).To explain this discrepancy, it has been proposed that elPB neurons might have long dendrites that extend into the external nuclear layer where spinal and trigeminal afferents terminate (Blomqvist et al., 1989;Saper, 1995). There is ultrastructural evidence that spinal and trigeminal afferents contact amygdala projection neurons in the lateral parabrachial area (Ma and Peschanski, 1988), but in this study, neither the laminae of origin of the spinal and trigeminal neur...