Heteroreceptor Complexes in the Central Nervous System. Focus on Their Role in Pain Modulation

Abstract

In the Central Nervous System there exist two major modes of communication, synaptic and volume transmission. A major mechanism for integration of synaptic and volume transmission signals is represented by allosteric receptor-receptor interactions (bidirectional, saturable, probe dependence) in heteroreceptor complexes operating in all neuro-glial networks including the pain circuits and peripheral nociceptors. These receptor—receptor interactions are characterized as follows: when the binding of a ligand to the orthosteric or allosteric sites of one receptor protomer causes, via direct allosteric interactions, a change in the ligand recognition, decoding, and trafficking processes of another receptor protomer in the heteroreceptor complex. Thus, this interaction leads to a change in receptor protomer functions. The opioid heteroreceptor complexes appear to play a major role as integrators of nociceptive and antinociceptive synaptic and volume transmission and may participate in the mediation of the antinociceptive actions of acupuncture. The MOR-DOR heteroreceptor complex is of special interest since the DOR protomer exerts an antagonistic allosteric influence on the MOR protomer function. This complex contributes to morphine-induced tolerance and dependence. D2likeR-MOR heteroreceptor complexes in the striatum and the limbic system contribute to antinociceptive actions by reducing activity in the stress and anxiety neuron system.