Application of nucleus pulposus to L 5 dorsal root ganglion in rats enhances nociceptive dorsal horn neuronal

Herniation of the nucleus pulposus (NP) from lumbar intervertebral discs commonly results in radiculopathic pain possibly via a neuroinflammatory response. NP sensitizes dorsal horn neuronal responses but it is unknown whether this reflects a central or peripheral sensitization. To investigate central sensitization we tested if NP enhances windup—the progressive increase in the response of a nociceptive spinal neuron to repeated electrical C-fiber stimulation—a phenomenon that may partly account for temporal summation of pain. Single-unit recordings were made from wide dynamic range (WDR; n =36) or nociceptivespecific (NS; n = 8) L5 dorsal horn neurons in 44 isoflurane anesthetized rats. Subcutaneous electrodes delivered electrical stimuli (20 pulses, 3x C-fiber threshold, 0.5 ms) to the receptive field on the hindpaw. Autologous NP was harvested from a tail disc and placed onto the L5 dorsal root ganglion after recording of baseline responses (n = 22). Controls had saline applied similarly (n = 22). Electrical stimulus trains (0.1,0.3 & 1 Hz; 5 min ISI) were repeated every 30 minutes for 3-6 hr following each treatment. The total number of evoked spikes (summed across all 20 stimuli) to 0.1 Hz was enhanced 3 hr post-NP, mainly in the after-discharge (AD) period (latency >400 msec). Total responses to 0.3 & 1.0 Hz were also enhanced at ≥ 60 min post-NP in both the C-fiber (100-400 msec latency) and AD periods, while the absolute windup (C-fiber + AD20x initial response) increased at ≥ 90 min post-treatment. In saline controls, windup was not enhanced at any time post-treatment for any stimulus frequency, although there was a trend toward enhancement at 0.3 Hz. These results are consistent with NP-induced central sensitization. Mechanical responses were not significantly enhanced after saline or NP treatment. We speculate that inflammatory agents released from (or recruited by) NP affect the DRG (and/or are transported to cord) to enhance primary afferent excitation of nociceptive dorsal horn neurons.