PATHOPHYSIOLOGY OF RADICULAR PAIN: WHEN AND WHERE PRF COULD MODULATE RADICULAR PAIN
Various experimental neuropathic pain models have shown the pain-relieving effect of PRF on mechanical hypersensitivity and thermal allodynia. This effect has been linked to the following events:
1. PRF elicited response at the dorsal horn:
PRF elicits a glial response at the dorsal horn, by reducing several microglial markers OX-42*, BDNF*, PI3K* and, p-ERK*.
These markers are signaling molecules secreted by activated microglia cells that not only drive aberrant pain processing and inflammation in the spinal cord but also underlie peripheral and central pain sensitization1-2.
2. PRF stimulation modulates calcium levels:
PRF electric fields promote Calcium uptake in cultured cells, thus potentially influencing calcium-dependent processes, such as synaptic communication, receptor activity, and calcium-dependent signaling pathways.
Reinforcing the latter, it has been shown that PRF may modulate the expression of the calcium-dependent peptide CGRP (Calcitonin gene-related peptide), which is a crucial player in the pain transduction pathway1,3
3. PRF suppresses pro-inflammatory EEAs release:
EEAs or Excitatory Amino Acids play a pivotal role in the development of the peripheral thermal and tactile hypersensitivity that drives the allodynic pain condition3,4
4. PRF triggers endogenous opioid analgesia:
The level of Met-Enkephalin, an endogenous opioid molecule, was found to be significantly increased in the dorsal horn in the first 24 hours after PRF applications1.
5. PRF modulates inhibitory descending pathways
Given that PRF analgesic effect on thermal allodynia is attenuated by the administration of noradrenaline and serotonin receptors antagonists; it is hypothesized that the pain relief associated with PRF may also involve the descending noradrenergic and serotoninergic inhibitory pathways; which are involved in the modulation of neuropathic pain1.