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

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.

The study aims to examine if retrograde signaling can induce hypersensitivity of primary afferent nociceptors and if hypersensitivity involves glial modulation.

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.

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.

Retrograde signaling may be one of the important mechanisms in neurogenic inflammation-mediated nociception, and this process is subjected to satellite glial modulation.