Understanding pain in depression.

A dysfunction of the serotonergic and noradrenergic pathways is commonly accepted as playing a major role in the aetiology of depression. Serotonergic cell bodies, located in the raphe nucleus, send projections to various parts of the brain where they are involved in the control of mood, movement, emotions such as anxiety and regulate behaviours such as eating, sexual activity and the feeling of pleasure. Similarly, the noradrenergic neurons, located in the locus coeruleus, project to the same regions where they regulate, in addition, attention and cognition. A further projection to the cerebellum regulates motor control. A dysfunction at the level of the monoamine neurons thus results in the classical symptoms of depression. In addition to these ascending pathways, however, the neurons in the raphe nucleus and the locus ceruleus also project to the spinal cord. These descending pathways serve to inhibit input from the intestines, the skeletal muscles and other sensory inputs. Under normal conditions, these inhibitory effects are modest, but in times of stress, in the interests of the survival of the individual, they can completely inhibit the input from painful stimuli. A dysfunction at the level of the serotonergic and noradrenergic neurons can thus affect both the ascending and descending pathways resulting in the psychological and somatic symptoms of depression but also in physical painful symptoms. 2004 John Wiley & Sons, Ltd.