Abstract
Several studies have shown that motor cortex stimulation provided pain relief by motor cortex plasticity and activating descending inhibitory pain control systems. Recent evidence indicated that the melanocortin-4 receptor (MC4R) in the periaqueductal gray played an important role in neuropathic pain. This study was designed to assess whether MC4R signaling existed in motor cortex- periaqueductal gray- spinal cord neuronal circuitry modulated the activity of sympathetic pathway by a virally mediated transsynaptic tracing study. Pseudorabies virus (PRV)-614 was injected into the left gastrocnemius muscle in adult male MC4R-green fluorescent protein (GFP) transgenic mice (n = 15). After a survival time of 4–6 days, the mice (n = 5) were randomly assigned to humanely sacrifice, and spinal cords and brains were removed and sectioned, and processed for PRV-614 visualization. Neurons involved in the efferent control of the left gastrocnemius muscle were identified following visualization of PRV-614 retrograde tracing. The neurochemical phenotype of MC4R-GFP-positive neurons was identified using fluorescence immunocytochemical labeling. PRV-614/MC4R-GFP dual labeled neurons were detected in spinal IML, periaqueductal gray and motor cortex. Our findings support the hypothesis that MC4R signaling in motor cortex-periaqueductal gray-spinal cord neural pathway may participate in the modulation of the melanocortin-sympathetic signaling and contribute to the descending modulation of nociceptive transmission, suggesting that MC4R signaling in motor cortex- periaqueductal gray-spinal cord neural pathway may modulate the activity of sympathetic outflow sensitive to nociceptive signals.
Highlights
Several studies have shown that motor cortex stimulation provided pain relief by motor cortex plasticity and activating descending inhibitory pain control systems[1,2]_ENREF_2
We found that injection of Pseudorabies virus (PRV)-614 into the gastrocnemius muscle resulted in retrograde infection of neurons in the intermediolateral cell column (IML) of spinal cord, periaqueductal gray (PAG) and motor cortex after spinal transection beneath L2 level
It was a strikingly attractive that PRV-614/melanocortin-4 receptor (MC4R)-green fluorescent protein (GFP) dual labeled neurons were detected in the IML, PAG and motor cortex
Summary
Several studies have shown that motor cortex stimulation provided pain relief by motor cortex plasticity and activating descending inhibitory pain control systems[1,2]_ENREF_2. Pagano et al [3] addressed that motor cortex stimulation produced its analgesic effects by enhancing neuronal firing rate and Fos immunoreactivity in the ipsilateral periaqueductal gray (PAG). Observations from Kerman et al suggested a novel role for the motor cortex and PAG in sympatho-motor integration[4]. A previous report considered that the main cause of motor cortex stimulationinduced antinociception was due to opioid participation in PAG[8]. Recent evidence indicated that melanocortinergic signaling in spinal cord and PAG played an important role in neuropathic pain[9,10,11]
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