René Descartes gave a colorful description of the mechanism of pain in the 17th Century: "Particles" of fire set in motion a spot on the skin of the foot, and by means of a "delicate thread" they open a "pore" at the other end, much like ringing a bell with a rope. The image has endured, perhaps because the shape of a pain signal's pathway from site of stimulus to brain still rings with some truth. The pathways – their transduction, transmission, interpretation, and modulation – are described in this section. Nociceptors at the frontline transduce a stimulus into an electrochemical signal and transmit the signal to the spinal cord and brain. Modulation along this path can check or exacerbate the signal, and may lead to chronic pain states. But, as Descartes implied, the brain is the ultimate interpreter, able to further modulate the signal and even to create pain without stimulus.