Fig. 2. Potential local circuit plasticity evoked by cholinergic and noradrenergic inputs in chronic pain.
(A) Acetylcholine is the one of the potential neuromodulators that drives circuit changes in chronic pain. Cholinergic input from basal forebrain projection neurons can differentially target each subtype of cortical GABAergic neurons. Vasoactive intestinal polypeptide (VIP) neurons are mainly located in L1 and L2/3, and, in particular, exhibit a higher expression of nicotinic receptors compared to other subtypes. In chronic pain, VIPs expressing nicotinic acetylcholine receptors (nAChR) can be driven by cholinergic inputs and reduce the net inhibitory effects on pyramidal neurons. Along with the action on nAChRs in VIP neurons, the activation of presynaptic nAChRs in thalamocortical neurons may modulate thalamocortical transmission in layer 4 of the S1 cortex in chronic pain. (B) Another potential factor is noradrenergic action of the S1 cortex during chronic pain conditions. Noradrenergic inputs projected from the locus coeruleus may exert layer-specific modulation by the action of different types of adrenergic receptors in the S1 cortex. Norepinephrine (NE) regulates the excitability of L1 and L2/3 excitatory neurons via presynaptic alpha-1 and alpha-2/beta-adrenergic receptors, respectively, on inhibitory neurons. In addition, NE modulates the synaptic responsiveness of L5 pyramidal neurons via alpha-1 receptors. NE may also act on presynaptic thalamocortical neurons, resulting in local circuit plasticity.
© Korean J Physiol Pharmacol