last updated 17-04-2024

Pain pathway

Pathways leading to final pain perception

The first step in the perception of pain is activation of nociceptors in the painful area (transduction). A stimulus activates the receptor of the nociceptor and an action potential is generated and conducted towards the central nervous system by afferent neurons. There are two types of neurons: the Aδ-neurons and the C-neurons. The former are myelinated neurons which measure 1-5μm in diameter; they have a quick conductance of action potentials. These neurons are responsible for quick, sharp pain (fast fiber pain). The latter are unmyelinated neurons with a small diameter (0,3μm) and have a relatively slow conductance of action potentials (slow fiber pain). C-neurons react to mechanic, thermal and chemical stimuli and are responsible for deep, arching and poorly localised (slow fiber) pain. Cell bodies of the nociceptive neurons are localised in the spinal ganglia.



The second step in pain perception is the transmission of information from the nociceptors to the spinal cord. The afferent nociceptive neurons connect in the dorsal horn of the spinal cord to a complex of other neurons. When the pain signal is transported further, the signal will first pass the anterior commissure to go to the brain on the contralateral side.

The third step is the onward transmission of pain information to higher brain centres. The signal can enter the brain via the spinothalamic tract. This tract projects via the medulla and midbrain to the thalamus, which projects further to the somatosensory cortex and limbic system.

Pharmacological treatment of pain is focused on decrease of pain stimulators at the level of nociceptors (prostaglandin synthesis inhibitors), inhibition of transmission of action potentials (local anaesthetics, transcutaneous electrical nerve stimulation) and central modulation (opioids).


C-neurons transduce acute sharp pain.


Local anaesthetics act at the level of the brain. 


Aδ-neurons conduct quickly because the action potential does NOT have to pass the nodes of Ranvier.