Is the Experience of Thermal Pain Genetics Dependent?

Figure 1

Peripheral and central modulation of the nociceptive signal. Serotonin receptors as well as transient receptor potential (TRP) channels in the periphery are activated in response to a nociceptive stimuli and enable the generation of an action potential. Signals will be propagated through the primary afferent neuron reaching the first synapse at the dorsal horn of the spinal cord. Centrally the nociceptive signal is controlled by descending pathways. Inhibitory descending serotonin released in the dorsal horn can either bind with serotonin receptor located in the primary afferent neuron inhibiting the first synapse; bind to serotonin receptor 7 and/or 3 activating the inhibitory interneuron; or bind with serotonin receptor in the spinothalamic neuron. The nociceptive signal can be also inhibited by binding of descending dopamine with its receptor D2/D3 in the primary afferent and/or in the spinothalamic neuron or by binding of opioids with receptors and μ in either the primary afferent or in the spinothalamic neuron. Pain signals can also be facilitated by central descending pathways, in which serotonin can excite the primary afferent neuron by binding with serotonin receptors 7, 3, and . Serotonin can also bind with receptor inhibiting the inhibitory interneuron or with serotonin receptor 3 located either in the excitatory interneuron or in the spinothalamic neuron, enhancing the nociceptive signal. Dopamine has also a facilitatory effect by binding with receptor D1 located either in the primary afferent or in the spinothalamic neuron. MAO and COMT can participate in the inhibitory and facilitatory nociceptive signaling by regulating the degradation of either serotonin or dopamine in the presynaptic neuron.