Central Sensitization and Aberrant Nerve Sprouting Possible Explanations for RFA Failure of MBDR in CLBP of FJ Origin: CRF Versus WCRF or PRF-DRG Randomized Clinical Trial

The efficacy of radiofrequency to treat LBP of FJ origin decreases with time, and the pathophysiological mechanisms behind this failure is a matter of debate; the phenomenon of central sensitization and ectopic nerve regeneration could be possible explanations.

Central sensitization represents an enhancement in the function of neurons and circuits in nociceptive pathways caused by increases in membrane excitability and synaptic efficacy as well as to reduced inhibition and is a manifestation of the remarkable plasticity of the somatosensory nervous system in response to activity, inflammation, and neural injury. The net effect of central sensitization is to recruit previously subthreshold synaptic inputs to nociceptive neurons, generating an increased or augmented action potential output: a state of facilitation, potentiation, augmentation, or amplification. Central sensitization is responsible for many of the temporal, spatial, and threshold changes in pain sensibility in acute and chronic clinical pain settings and exemplifies the fundamental contribution of the central nervous system to the generation of pain hypersensitivity. Because central sensitization results from changes in the properties of neurons in the central nervous system, the pain is no longer coupled, as acute nociceptive pain is, to the presence, intensity, or duration of noxious peripheral stimuli. Instead, central sensitization produces pain hypersensitivity by changing the sensory response elicited by normal inputs, including those that usually evoke innocuous sensations.

In previous studies using animal models of low back pain, mechanical allodynia has been correlated with and is hypothesized to be due to a host of physiologic changes in the central nervous system. Among these nociceptive responses are neuronal plasticity, glial cell activation and cytokine upregulation. In addition, animal models specifically investigating changes in neural electrical activity following lumbar facet capsule stretching have demonstrated alterations in neurophysiology for applied loading. Together, these molecular and cellular changes contribute to central sensitization and persistent pain. Indeed, in clinical research, central sensitization has been hypothesized as a mechanism of chronic pain after whiplash injury.

Injury to the cervical facet joint and its capsule is primarily a ligamentous injury but because the facet capsule is innervated there may also be neuropathic injury. In fact, capsule stretch in several animal models induces both transient increases in firing of joint-innervating afferents similar to the injury discharge that accompanies nerve injury and also the later development of ectopic firing and hyperexcitability in dorsal horn neurons. The onset of spontaneous firing likely represents a temporal threshold after which sensitization persists despite blockade of joint afferent activity with nerve blocks or neurotomy.

Patients with chronic pain exhibit primary mechanical hyperalgesia over the back of the cervical spine, in a "coat hanger" distribution indicative of peripheral nociceptor sensitization. These patients are also hypersensitive to pressure, heat, and cold stimuli at sites distant from the cervical spine, including over the median, radial, and ulnar nerve trunks in the arm and over the tibialis anterior muscle. Together, these studies demonstrate that generalized and widespread secondary hypersensitivity is robust in individuals who sustain a whiplash-like exposure and indicative of central sensitization. Patient-reported sensory disturbances include spontaneous pain that is disproportionate to and/or occurs in the absence of any inciting event.