Descending pain pathways and central sensitization. Descending pain pathways and central sensitization modulate the pain response in the dorsal horn of the spinal cord. Descending analgesic pathways include the serotonin-norepinephrine and opioidergic descending pathways, which dampen pain sensitivity response. Loss of descending analgesia leads to hyperalgesia and allodynia. Central sensitization occurs through the action of glutamate on the N-methyl-D-aspartate (NMDA) receptor, resulting in an increase in intracellular calcium levels and kinase activation, leading to hyperalgesia and allodynia.