BackgroundChronic bone cancer pain is thought to be partly due to central sensitization. Although murine models of bone cancer pain revealed significant neurochemical changes in the spinal cord, it is not known whether this produces functional alterations in spinal sensory synaptic transmission. In this study, we examined excitatory synaptic responses evoked in substantia gelatinosa (SG, lamina II) neurons in spinal cord slices of adult mice bearing bone cancer, using whole-cell voltage-clamp recording techniques.ResultsMice at 14 to 21 days after sarcoma implantation into the femur exhibited hyperalgesia to mechanical stimuli applied to the skin of the ipsilateral hind paw, as well as showing spontaneous and movement evoked pain-related behaviors. SG neurons exhibited spontaneous excitatory postsynaptic currents (EPSCs). The amplitudes of spontaneous EPSCs were significantly larger in cancer-bearing than control mice without any changes in passive membrane properties of SG neurons. In the presence of TTX, the amplitude of miniature EPSCs in SG neurons was increased in cancer-bearing mice and this was observed for cells sampled across a wide range of lumbar segmental levels. Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor- and N-methyl-D-aspartate (NMDA) receptor-mediated EPSCs evoked by focal stimulation were also enhanced in cancer-bearing mice. Dorsal root stimulation elicited mono- and/or polysynaptic EPSCs that were caused by the activation of Aδ and/or C afferent fibers in SG neurons from both groups of animals. The number of cells receiving monosynaptic inputs from Aδ and C fibers was not different between the two groups. However, the amplitude of the monosynaptic C fiber-evoked EPSCs and the number of SG neurons receiving polysynaptic inputs from Aδ and C fibers were increased in cancer-bearing mice.ConclusionsThese results show that spinal synaptic transmission mediated through Aδ and C fibers is enhanced in the SG across a wide area of lumbar levels following sarcoma implantation in the femur. This widespread spinal sensitization may be one of the underlying mechanisms for the development of chronic bone cancer pain.

Object The authors sought to quantify the clinical outcome of microscopic lumbar spinous process–splitting laminectomy in patients with lumbar spinal stenosis (LSS). They performed a microscopic laminectomy in which the spinous process is split longitudinally into 2 halves. For single-level decompression, they inserted a tubular retractor between the split process. Methods Data obtained in a total of 124 patients were retrospectively analyzed. Patients were divided into 2 groups: the “slip” group, comprising patients with spondylolisthesis-type LSS with vertebral body slippage (Group 1), and the “nonslip” group, comprising patients with spondylosis-type LSS without vertebral body slippage or with LSS due to central protrusion of lumbar disc herniation. Clinical outcome in all patients was evaluated by using the Japanese Orthopaedic Association score. In the slip group, slippage and instability rates were evaluated by using pre- and postoperative dynamic radiographs in the sagittal plane. Postoperative CT images were used to evaluate bony union at 2 sites: a region between the left and right portions of the halved spinous process and a region between the base of the halved process and vertebral arch. Signal intensity of the multifidus muscle at individual decompression levels was evaluated on pre- and postoperative T1- and T2-weighted MR images. Results Preoperative clinical symptoms improved significantly after surgery in all patients. Slippage and instability rates in the slip group showed no significant differences when pre- and postoperative conditions were compared. Union rates at the region between the left and right portions of the halved process and the region between the base of the halved process and vertebral arch were 97.1% and 82.5%, respectively. Magnetic resonance imaging showed only a small amount of fat infiltration in the multifidus muscle after surgery in 12.2% of cases. Conclusions The authors recommend microscopic lumbar spinous process–splitting laminectomy as a promising minimally invasive surgery for the treatment of LSS.

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