BACK pain affects 50–80% of adults at some point in their lives; the cause is unknown in approximately 85% of the cases.1However, mechanical deformation of the dorsal root ganglion (DRG) and its nerve roots is a possible consequence of certain disorders, such as spinal stenosis, disc herniation, degenerative disorder, spinal injury, or tumors.2Recently, it was discovered that radicular pain behaviors such as thermal hyperalgesia and mechanical allodynia develop in rats after a chronic compression injury of the ipsilateral DRG (chronic compression model [CCD]) produced by the implantation of a metal rod in the intervertebral foramen.3,4Ectopic discharges originating in the compressed ganglion were electrophysiologically recorded from dorsal root fibers and from the somata of the DRG neurons.3–5This suggests that anatomic abnormalities are an important factor in the development of radicular back pain. In the current issue of Anesthesiology, Gu et al.  6describe a modified CCD model created by compressing the DRG with SURGIFLO™ (Johnson & Johnson, Somerville, NJ), a hemostatic gelatin matrix. SURGIFLO™ hardens within a minute or two after injection and has been extensively and safely used in surgical operations. Rats subjected to DRG compression with SURGIFLO™ develop thermal hyperalgesia and mechanical allodynia that last more than 30 days. The benefit of using the biologically degradable SURGIFLO™ as compared with a metal rod is that the texture of the SURGIFLO™ is similar to that of herniated disc and thus it can better mimic some clinical conditions.

Inflammatory responses in the compressed DRG play key roles in the development of radicular pain. In their study, Gu et al.  demonstrated that the level of an inflammatory marker (Iκβ-α) was up-regulated in both the compressed DRG and the adjacent spinal cord. Epidural administration of the corticosteroid triamcinolone effectively reduced the increased cutaneous sensitivity in the SURGIFLO™ CCD rats, suggesting an important role of inflammation in the development of the painful behaviors in this model. Consistent with findings from the study of Gu et al. , Homma et al.  7reported previously in a modified CCD model that DRG compression–induced mechanical allodynia can be partially blocked by simultaneous local administration of soluble tumor necrosis factor-α receptors to the compressed DRG. Local application of inflammatory cytokine, tumor necrosis factor α, to a normal DRG, on the other hand, induced mechanical allodynia similar to that of CCD rats. In another study, White et al.  8demonstrated increased expression of a chemokine, monocyte chemoattractant protein 1 and its receptor, chemokine (c-c motif) receptor 2, in the compressed DRG. Application of monocyte chemoattractant protein 1 to the cell bodies of the intact formerly compressed DRG produced potent excitatory effects not observed in control ganglia.

Clinically, the severity of pain may not correlate with the degree of disc herniation or mechanical deformation of the DRG. There is a subgroup of patients with lumbar radiculopathy who have minimal abnormality of the external morphology of the anulus and yet present with leg pain, paresthesias, and signs of dural irritation. Corticosteroids may have a dramatic effect on the pain of patients with either major or minor morphologic disc abnormalities, but no structural changes accompany their clinical improvement.9Therefore, inflammatory irritation per se  (i.e. , in the absence of mechanical compression) is sufficient to cause radicular back pain. In laboratory animals, radiculopathy can occur when the DRGs are inflamed by mere exposure to materials released from the nucleus pulposus,10which is known to possess immunogenic and chemogenic capacities.11To examine inflammation as the cause of radiculopathy, Xie et al.  12recently developed a rat model of radicular pain by local inflammatory irritation of the DRG (localized inflammation model). The localized inflammation model involves depositing a drop of the immune activator zymosan over a single DRG. This results in a robust, prolonged state of mechanical allodynia, generation of ectopic discharges, extensive sympathetic sprouting, and elevation of inflammatory cytokines in the inflamed DRG.

Gu et al.  also demonstrated an up-regulation of the N -methyl-d-aspartate receptor, NR1, in compressed ganglia and the adjacent spinal dorsal horn. N -methyl-d-aspartate receptors are known to play important roles in various pathologic pain states resulting from peripheral nerve injury, because of their involvement in central sensitization. Results from the current study demonstrated for the first time that N -methyl-d-aspartate receptors in the spinal cord and the injured DRG may be a contributing factor in radicular pain, although further study is necessary to prove that increased NR1 expression is related to the pain behaviors.

In summary, laboratory and clinical studies have suggested that both mechanical deformation and inflammatory irritation of sensory ganglia are involved in radicular low back pain. Gu et al.  have developed a modified CCD model that may help in studying radicular back pain. In addition, they have provided new evidence supporting a major role of inflammatory responses in the development of radicular pain. Further studies are needed to explore the exact mechanism of radicular pain in disc herniation and CCD models.

*Pain Research Center, Department of Anesthesiology, †Department of Anesthesiology, University of Cincinnati College of Medicine, Cincinnati, Ohio.

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