Abstract
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Objectives: Annexin V a marker of apoptosis can also bind to sites of cellular stress in which there are relatively low potentially reversible levels of phosphatidylserine (PS) expression in contrast to high levels seen with frank apoptosis. Neuronal-axonal stress and conduction abnormalities are major components of chronic pain. We wished to see if annexin V could image sites of stress in a well described rodent model of pain.
Methods: Adult Sprague-Dawley rats underwent ligation and excision of 2mm segments of two of three nerves of the posterior-tibial trifurication preserving the remaining sural nerve (SNI = spared nerve injury). 1 week later rats were co-injected with 2-3 mCi of Tc99m-annexin V-128 and 40 ug of Cy5.5-annexin V-128 while under inhalation anesthesia. SPECT was performed one hour after injection of tracer and animals were sacrificed while sedated via CO2 inhalation. Brain, spine and lower extremity nerves were removed for autoradiography and fluorescent imaging.
Results: Control rats (n=3) showed little regional variation of annexin uptake (< 10%) at SPECT, autoradiographic or fluorescent imaging. Chronic pain rats (n=4) however had 2 to 3 fold increases (p=0.013) in uptake of left lower extremity nerves, right lateral and dorsal spinal pain tracts, and curiously the right or left thalamic-hippocampal and sensory cortical regions.
Conclusions: Annexin V can detect neuronal/axonal stress-conduction abnormalities that reflect chronic pain in the peripheral and central nervous system. Processing of pain stimuli follows the expected distribution in the peripheral nerves and spinal cord however seem to localize to both contralateral or the ipsilateral midbrain and cortical regions. Further studies to better define spatio-temporal changes of annexin V uptake in SNI pain models are ongoing.
Research Support: EB000898 FB, CA102348 (JFT & FB)
- Society of Nuclear Medicine, Inc.