Pain consists of sensory-discriminative and negative-affective components.
Neuronal mechanisms for the sensory component of pain have been investigated
extensively. On the other hand, neuronal mechanisms for the affective component of
pain remain to be investigated. Recent behavioral studies have revealed the brain
regions and neuronal mechanisms involved in the affective component of pain.
Glutamatergic transmission within the anterior cingulate cortex and basolateral
amygdaloid nucleus plays a critical role in pain-induced aversion. Noradrenaline and
corticotropin-releasing factor (CRF) within the ventral and dorsolateral parts of the bed
nucleus of the stria terminalis (BNST), respectively, play important roles in paininduced
aversion. Electrophysiological studies have revealed that both noradrenaline
and CRF activate type II BNST neurons, which may inhibit the BNST output neurons.
A recent histochemical study showed that most VTA-projecting BNST output neurons
are GABAergic neurons, which preferentially make synaptic contact with VTA GABAergic neurons. Therefore,
activation of VTA-projecting BNST output neurons should increase the neuronal excitability of VTA
dopaminergic (DAergic) neurons through increased inhibitory input to VTA GABAergic neurons, which
negatively regulate VTA DAergic neurons. Pain-induced release of noradrenaline and CRF within the BNST
may activate type II BNST neurons, which could suppress VTA-projecting BNST output neurons, thereby
attenuating the excitatory influence to the VTA DAergic neurons. Recent optogenetic studies suggest that the
suppression of VTA DAergic neurons is sufficient to induce place aversion. Pain-induced place aversion may
be due to the suppression of VTA DAergic neurons via the processing of nociceptive information within the
Keywords: Bed nucleus of the stria terminalis, depression, dopamine, emotion, extended amygdala, noradrenaline,
pain, ventral tegmental area.
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