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Application of Nucleus Pulposus to L₅ Dorsal Root Ganglion in Rats Enhances Nociceptive Dorsal Horn Neuronal Windup

¹Section of Neurobiology, Physiology and Behavior and ²Department of Anesthesiology and Pain Medicine, University of California, Davis, California

Submitted 27 July 2004; accepted in final form 1 March 2005

Herniation of the nucleus pulposus (NP) from lumbar intervertebral discs commonly results in radiculopathic pain possibly through a neuroinflammatory response. NP sensitizes dorsal horn neuronal responses, but it is unknown whether this reflects a central or peripheral sensitization. To study 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 nociceptive-specific (NS; n = 8) L₅ dorsal horn neurons in 44 isoflurane-anesthetized rats. Subcutaneous electrodes delivered electrical stimuli (20 pulses, 3 times the 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, and 1 Hz; 5-min interstimulus interval) were repeated every 30 min for 3–6 h after each treatment. The total number of evoked spikes (summed across all 20 stimuli) to 0.1 Hz was enhanced 3 h after NP, mainly in the after-discharge (AD) period (latency > 400 ms). Total responses to 0.3 and 1.0 Hz were also enhanced at 60 min after NP in both the C-fiber (100- to 400-ms latency) and AD periods, whereas the absolute windup (C-fiber + AD – 20 times the initial response) increased at 90 min after treatment. In saline controls, windup was not enhanced at any time after 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 dorsal root ganglion (and/or are transported to cord) to enhance primary afferent excitation of nociceptive dorsal horn neurons.

This article has been cited by other articles:

				Y. Guan, J. Borzan, R. A. Meyer, and S. N. Raja Windup in dorsal horn neurons is modulated by endogenous spinal mu-opioid mechanisms. J. Neurosci., April 19, 2006; 26(16): 4298 - 4307. [Abstract] [Full Text] [PDF]