A systematic review on descending serotonergic projections and modulation of spinal nociception in chronic neuropathic pain and after spinal cord stimulation

Chronic neuropathic pain is a condition where the nervous system is damaged, leading to pain. Current treatments are not very effective, making it important to understand the mechanisms involved. One such mechanism is the descending serotonergic system, which affects pain signaling in the spinal cord. This review looks at how serotonin, a key neurotransmitter, influences pain signals in the spinal cord, both in normal conditions and in chronic neuropathic pain. It also examines how spinal cord stimulation (SCS), a treatment for neuropathic pain, impacts this serotonergic system. The findings suggest that targeting specific serotonin receptors could improve treatments for neuropathic pain. Novel SCS methods may also benefit from understanding how they affect the descending serotonergic system, potentially leading to more effective pain relief.

• 1
  In healthy rodents, serotonin generally inhibits pain signals in the spinal cord via receptors like 5-HT1a, 5-HT1b, 5-HT2c, 5-HT3, and 5-HT4.
• 2
  In neuropathic pain, this system can switch to facilitating pain signals, involving receptors like 5-HT2a, 5-HT2b, and 5-HT3. This shift is linked to changes in serotonin levels and receptor expression after nerve injury.
• 3
  Spinal cord stimulation can restore the inhibitory function of the serotonergic system, reducing pain. This involves receptors like 5-HT2, 5-HT3 and 5-HT4, potentially reversing the changes caused by neuropathic pain.