Painful stimuli evoke not only discrete sensory perceptions and motor responses but also marked changes in emotional and autonomic states. An understanding of the neuronal basis of pain behaviour needs a precise knowledge of the pathways that transmit nociceptive messages from the periphery to higher centres. From the periphery, nociceptive primary Aδ and C thin fibres terminate mainly in the superficial dorsal horn (laminae I and II). Lamina I axons ascend through the controlateral lateral (rodents)/ventrolateral (primates) funiculus of the spinal cord and give rise to two primary nociceptive pathways. The first one reaches the thalamus and would be rather involved in the somatosensory discriminative aspect of pain. The second one, which targets the parabrachial area, retains our attention here because it would be essential in genesis of the autonomic as well as the emotional components of pain.

The spino-parabrachial circuits. The heaviest projection from lamina I neurons, in the brainstem, terminates at the ponto-mesencephalic level, in the lateral parabrachial area (PB). High proportions of both lamina I spino-PB and PB neurons are driven by Aδ and C fibres and respond specifically to noxious stimuli. These neurons encode thermal as well as mechanical stimuli within the noxious range, a smaller proportion of them being also responsive to cooling. The receptive fields of spino-PB neurons are generally small (one or two toes), whereas those for PB neurons are larger (a limb to the whole body), probably indicating that there is a large convergence of lamina I inputs onto this region. The PB neurons also respond to visceral noxious stimuli receiving often a strong convergence of somato-visceral inputs. Responses to noxious stimuli were depressed by intravenous morphine in dose-dependent fashion.

Using restricted injections of the anterograde tracer, Phaseolus vulgaris leucoagglutinin, we have shown, in the rat, that the nociceptive portion of the PB area has two main targets in the forebrain, the amygdala and the hypothalamus, and two significant targets in the brainstem, the periaqueductal grey matter and the ventrolateral medulla.

In the amygdala, the ‘nociceptive’ projections from the PB area target the lateral capsular division and to a lesser extent the lateral division of the central nucleus. This area of the amygdala contributes probably to specific components of aversive emotions, for example, the anxiety and the fear-evoked avoidance learning that occur in the face of dangerous or traumatic situations. Activation of the PB-amygdaloid connection by noxious inputs could be the link through which pain-related emotional reactions are triggered.

In the hypothalamus, the ‘nociceptive’ projections from the PB area target the ventromedial nucleus and, to a lesser extent, the retrochiasmatic area. The ventromedial hypothalamic nucleus corresponds to the satiety centre. This nucleus, together with the dorsal periaqueductal grey matter, has also been described as a major centre for rage and aggressive behaviours. Importantly, the ventromedial nucleus projects densely to the dorsal periaqueductal grey. This PB-hypothalamic-peri-aqueductal loop appears likely to be involved in the production of highly aversive behaviours. Thus the PB-hypothalamic tract could play an important role in motivational behaviour, such as defence, aggression and flight. An additional action in homeostatic preservation of the energy metabolism in response to cooling (catabolism of brown fat) and/or noxious stimulation (disruption of feeding) must also be envisaged.

In the periaqueductal grey, the ‘nociceptive’ projections from the PB area terminate in the lateral and the dorsomedial columns. The lateral column is involved in active emotional coping strategy that is characterized by an engagement with the environment (confrontation, fight, and flight), a sympatho-excitation (hypertension, tachycardia), and a short-lasting non-opioid analgesia. The dorsomedial column, although much less studied, seems to be involved in strongly aversive (and even ‘explosive’) behaviours. The convergence of both PB and lamina I projections upon the lateral periaqueductal quadrant could play a key role in triggering the aversive behaviour, the autonomic responses and the analgesia needed to cope with noxious aggression of threat.

In the ventrolateral medulla, the ‘nociceptive’ projections from the PB area extend along its entire length. The area, located between ambiguous and lateral reticular nuclei, is a major sympathetic cardiovascular centre. Stimulation of the PB region that projects to the ventrolateral medulla can produce a dramatic increase in blood pressure. Thus the PB-ventrolateral medulla link, together with the less dense direct spino-medullary pathway (stemming from laminae I, V-VII), could be critical in initiating the cardiovascular changes, which occur almost immediately in response to noxious stimuli.

Taken together these results suggest that the spino-parabrachial tract is a major contributor to the emotional, autonomic features of the pain experience. The parabrachial area would act as a conductor that collects a very high rate of nociceptive messages, which converge at least in part, with autonomic messages arising from the nucleus solitary tract. After processing in the parabrachial area, this information would be distributed to key areas of the brain that trigger emotions (amygdala), emotional motor components (periaqueductal grey), and autonomic homeostatic adaptations (hypo-thalamus, ventrolateral medulla) in response to noxious stimuli and/or major autonomic disturbances.