
Central sensitization: analysis by physio meets science.
Neurophysiological Mechanism of Central Sensitization in the Spinal Cord following Surgery:
Central sensitization was first described by Woolf in 1983 (https://pubmed.ncbi.nlm.nih.gov/6656869/) as a form of long-term adaptive neuroplasticity that amplifies the transmission of nociceptive information by affecting spinal cord neurons and is believed to be a principal neurophysiological mechanism with regard to pain persistence.
Peripheral nociception can trigger a prolonged increase in the excitability of dorsal root ganglia (DRG) neurons, which transmit nociceptive signals to the spinal cord, resulting in central sensitization.
This condition involves heightened responsiveness of spinal neurons, driven by signaling molecules like adenosine triphosphate (ATP) and neurotransmitters such as glutamate (Glu) and substance P (SP).
These molecules activate specific receptors on spinal neurons, including purinergic receptor 2 (P2-R), N-methyl-D-aspartate receptor (NMDAR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), and neurokinin 1 receptor (NK1R).
The activation of these receptors sets off a cascade of intracellular pathways involving enzymes like calcium/calmodulin-dependent protein kinase II (CaMKII), protein kinase C (PKC), protein kinase A (PKA), mechanistic target of rapamycin (mTOR), phosphoinositide 3-kinase (PI3K), and extracellular signal-regulated kinases 1/2 (ERK1/2), all of which amplify the transmission of nociceptive signals to the brain.