Neuronal hyperexcitability in the dorsal horn after painful facet joint injury

Abstract

Excessive cervical facet capsular ligament stretch has been implicated as a cause of whiplashassociated disorders following rear-end impacts, but the pathophysiological mechanisms that produce chronic pain in these cases remain unclear. Using a rat model of C6/C7 cervical facet joint capsule stretch that produces sustained mechanical hyperalgesia, the presence of neuronal hyperexcitability was characterized 7 days after joint loading. Extracellular recordings of spinal dorsal horn neuronal activity between C6 and C8 (117 neurons) were obtained from anesthetized rats, with both painful and non-painful behavioral outcomes established by the magnitude of capsule stretch. The frequency of neuronal firing during noxious pinch (p<0.0182) and von Frey filaments applications (4-26 g) to the forepaw was increased (p<0.0156) in the painful group compared to the non-painful and sham groups. In addition, the incidence and frequency of spontaneous and afterdischarge firing were greater in the painful group (p<0.0307) relative to sham. The proportion of cells in the deep laminae that responded as wide dynamic range neurons also was increased in the painful group relative to non-painful or sham groups (p<0.0348). These findings suggest that excessive facet capsule stretch, while not producing visible tearing, can produce functional plasticity of dorsal horn neuronal activity. The increase in neuronal firing across a range of stimulus magnitudes observed at day 7 post-injury provides the first direct evidence of neuronal modulation in the spinal cord following facet joint loading, and suggests that facet-mediated chronic pain following whiplash injury is driven, at least in part, by central sensitization.

Riluzole effects on behavioral sensitivity and the development of axonal damage and spinal modifications that occur after painful nerve root compression

“…6), reflecting an increase in the number of neurons that respond to noxious stimuli. 25,28,37,55,56,64,72 It is possible that the increased number of WDR neurons together with the elevated CGRP expression in the deep laminae may act to enhance the neuronal excitability that develops after a painful root compression (Figs. 3, 5, and 6).…”

“…Mechanoreceptive neurons innervating the forepaw were searched for by lightly brushing the plantar surface of the forepaw and slowly advancing the probe through the deep laminae (400-1000 mm below the pial surface) until a neuron responsive to the light brushing was found. 19,25,56 Once a neuron was identified, a sequence of 6 mechanical stimuli was applied to the forepaw: 1) 10 light brush strokes with a brush applied over 10 seconds; 2-5) a series of 4 von Frey filaments (1.4, 4.0, 10.0, 26.0 gf), each applied 5 times for 1 second with a 1-second rest between applications; and 6) a 10-second, 60-gf pinch by a microvascular clip (Roboz, Inc.). 56 There was a 60-second rest between applications of each of the different stimuli.…”

“…For statistical analysis, the spike count was log-transformed because of a positive skew in the data distribution. 56 Separate mixed-effect 1-way ANOVAs with Tukey HSD post hoc tests were used to compare the differences in the number of action potentials that were evoked by each filament between groups; neurons were nested within rats and rats were nested in groups. A mixed-effect 1-way ANOVA with the same levels of nesting was used to test for differences between groups for the depth at which the neurons were recorded.…”

The Physiological Basis of Cervical Facet-Mediated Persistent Pain: Basic Science and Clinical Challenges

“…12,17,27,41,43,55,57,71 Mechanical stretch of the facet to failure (mean ± SD, 72.9% ± 7.1% strain) produces morphological abnormalities (ie, focal swelling, vacuolations, and terminal retraction balls) in the axons innervating the facet capsule in the goat. 43 However, as described above, subfailure stretch of the facet capsule exceeding physiologic strains is sufficient to damage the ligament's microstructure and induce pain.…”

“…The initial injury-induced hyperexcitability of dorsal horn neurons that develops by 24 hours after injury persists for at least 7 days in the rat. 17,19,71 The sustained hyperexcitability of spinal neurons has been speculated to be maintained by structural and/or functional plasticity in the spinal cord. 4,51 Indeed, structural plasticity is evident in the superficial dorsal horn, with approximately a 50% increase in the number of excitatory synapses that are present in the spinal cord, accompanied by a decrease in inhibitory synapses.…”