Minocycline Inhibits the Enhanced Antidromic Stimulation-induced Sensitization of C-Fibers Following Intradermal Capsaicin Injection

Background: Our previous studies indicated that retrograde signaling initiating from the spinal cord was mediated by the plasticity of Dorsal Root Ganglion (DRG) neurons. Both retrograde signaling and neuronal plasticity contributed to neurogenic inflammation, which were modulated by the activity of Satellite Glial Cells (SGCs). Thus, we want to know whether retrograde signaling is involved in the hypersensitivity of nociceptive afferents, and whether this process is affected by the plasticity of DRG neurons and glia. Objective: The study aims to examine if retrograde signaling can induce hypersensitivity of primary afferent nociceptors and if hypersensitivity involves glial modulation. Methods: Antidromic Electrical Stimulation (ES) of dorsal roots was used to mimic retrograde signaling activity. C- primary nociceptive afferent activity was recorded for testing the effect of antidromic ES. In a separate group, intradermal capsaicin injection to the ipsilateral hindpaw was used to prime DRG nociceptive neurons. For the third group, a glial inhibitor, minocycline, was pre-administered to test glial modulation in this process. Results: Antidromic ES sensitized the responses of C-fibers to nociceptive mechanical stimuli. For rats subjected to intradermal capsaicin injection, C fibers experienced more drastic sensitization induced by antidromic ES, shown as a greater response and longer duration, implying that sensitization correlates with the activation of DRG neurons. Minocycline pretreatment significantly blocked the priming effect of capsaicin on C-fiber sensitization induced by antidromic ES, indicating the involvement of SGCs in DRG neuronal sensitization. Conclusion: Retrograde signaling may be one of the important mechanisms in neurogenic inflammation-mediated nociception, and this process is subjected to satellite glial modulation.

Mechanisms of blood flow regulation of in the skin during stimulation of the spinal cord in humans

Changes of the blood flow in the shin skin in the case of 12 healthy subjects by laser doppler flowmetry were observed under transcutaneous electrical spinal cord stimulation (TSCS) by subthreshold bipolar pulses with a frequency of 30 Hz were detected. It was found that the TSCS in the area of the vertebrae T11 and L1 leads to a significant increase in skin blood flow. With a stimulus intensity of 90% of the motor threshold, the microcirculation rate increased by more than 85% relative to baseline.The results of the study show that the stimulation of blood flow in the skin by TSCS is realized mainly due to the antidromic stimulation of sensory nerve fibers. An important mediator that contributes to vasodilation and increase of cutaneous blood flow in PSCS is nitric oxide (NO), which is predominantly endothelial in origin.

Identification of single neurons in a forebrain network

Behaviors are generated from complex interactions among networks of neurons. Single-unit ensemble recording has been used to identify multiple neurons in functioning networks. These recordings have provided insight into interactions among neurons in local and distributed circuits. Recorded units in these ensembles have been classed based on waveform type, firing pattern, and physical location. To identify individual projection neurons in a cortical network, we have paired tetrode recording with antidromic stimulation. We developed techniques that enable antidromic identification of single units and study of functional interactions between these neurons and other circuit elements. These methods have been developed in the zebra finch and should be applicable, with potential modifications that we discuss here, to any neural circuit with defined subpopulations based on projection target. This methodology will enable elucidation of the functional roles of single identified neurons in complex vertebrate circuits.

Antidromic Activation Reveals Tonotopically Organized Projections From Primary Auditory Cortex to the Central Nucleus of the Inferior Colliculus in Guinea Pig

The inferior colliculus (IC) is highly modulated by descending projections from higher auditory and nonauditory centers. Traditionally, corticofugal fibers were believed to project mainly to the extralemniscal IC regions. However, there is some anatomical evidence suggesting that a substantial number of fibers from the primary auditory cortex (A1) project into the IC central nucleus (ICC) and appear to be tonotopically organized. In this study, we used antidromic stimulation combined with other electrophysiological techniques to further investigate the spatial organization of descending fibers from A1 to the ICC in ketamine-anesthetized guinea pigs. Based on our findings, corticofugal fibers originate predominantly from layer V of A1, are amply scattered throughout the ICC and only project to ICC neurons with a similar best frequency (BF). This strict tonotopic pattern suggests that these corticofugal projections are involved with modulating spectral features of sound. Along the isofrequency dimension of the ICC, there appears to be some differences in projection patterns that depend on BF region and possibly isofrequency location within A1 and may be indicative of different descending coding strategies. Furthermore, the success of the antidromic stimulation method in our study demonstrates that it can be used to investigate some of the functional properties associated with corticofugal projections to the ICC as well as to other regions (e.g., medial geniculate body, cochlear nucleus). Such a method can address some of the limitations with current anatomical techniques for studying the auditory corticofugal system.