The Illustration above,
      . . . demonstrates the pathway in which Serotonin (5-HT), released by stimulation of a facilitator neuron, increases the ability of a sensory neuron to activate another neuron.   The effect of 5-HT is mediated through adenylate kinase and cyclic-Adenosyn Mono Phosphate (cAMP).   Phosphorylation of the K⁺ channel protein or a channel-binding protein, indicated by the circled P, closes the K⁺ channels, leading to prolonged depolarization of the sensory neuron.

      Sensitization occurs when the facilitator neuron is activated (by a noxious stimulus), in the absence of the conditioned stimulus (CS)(such as a lite touch);  it triggers activation of adenylate cyclase and the closing of K⁺ channels in the sensory neuron.   During the conditioning process, the rise in cAMP in the sensory neuron is much greater when the sensory neuron is triggered by the conditioned stimulus to generate an action potential just before the Unconditioned Stimulus (US) arrives.

      An adenylate cyclase activated both by the 5-HT receptor and by Ca²⁺-Calmoduline is the probable molecular site for convergence of the US and CS in the terminal of the sensory neuron.   The brief Ca²⁺ influx, triggered by the CS and the subsequent action potential in the sensory neuron, activates this adenylate cyclase.   5-HT released by the facilitator neuron, triggered by the US, also stimulates this cyclase.   However, activation to the cyclase and hence the increase in cAMP is greatest when the cyclase if first primed by Ca²⁺ influx and then, within 1 to 2 secs., activated by the binding of 5-HT.   In this way, the enhancement of adenylate cyclase activity triggered by the US makes the sensory neuron more sensitive to a conditioning stimulus;  the sensory neuron learns to associate the CS with the US and to respont to the CS alone with an enhanced response.