A Simulation Study on Selective Stimulation of C-Fiber Nerves for Chronic Pain Relief

It has been reported that stimulating nociceptive unmyelinated C nerves (<inline-formula> <tex-math notation="LaTeX">$C$ </tex-math></inline-formula>) near the sarcolemma could induce the secretion of endogenous opioids that relieve chronic pain. However, a substantial concern remains: concomitant stimulation might cause acute pain to nociceptive myelinated <inline-formula> <tex-math notation="LaTeX">$\text{A}\delta $ </tex-math></inline-formula> nerves (<inline-formula> <tex-math notation="LaTeX">$A\delta$ </tex-math></inline-formula>), which generally have a lower activation threshold than the <inline-formula> <tex-math notation="LaTeX">$C$ </tex-math></inline-formula>. However, few studies have reported on <inline-formula> <tex-math notation="LaTeX">$C$ </tex-math></inline-formula> selectivity over <inline-formula> <tex-math notation="LaTeX">$A\delta $ </tex-math></inline-formula> (<inline-formula> <tex-math notation="LaTeX">$C$ </tex-math></inline-formula>-selectivity). In this study, the <inline-formula> <tex-math notation="LaTeX">$C$ </tex-math></inline-formula> and <inline-formula> <tex-math notation="LaTeX">$A\delta $ </tex-math></inline-formula> nerves were modeled using the Hodgkin-Huxley (HH) and McIntyre-Richardson-Grill (MRG) models, respectively. Two potential stimulation schemes, including bipolar square waves and burst modulated alternating current, together with a new stimulation scheme named inhibit-<inline-formula> <tex-math notation="LaTeX">$A\delta $ </tex-math></inline-formula> (i-<inline-formula> <tex-math notation="LaTeX">$A\delta$ </tex-math></inline-formula>) that inhibits the excitability of the <inline-formula> <tex-math notation="LaTeX">$A\delta $ </tex-math></inline-formula>, were systematically investigated. Their stimuli were given to the <inline-formula> <tex-math notation="LaTeX">$C$ </tex-math></inline-formula> and <inline-formula> <tex-math notation="LaTeX">$A\delta $ </tex-math></inline-formula> nerves through point electrodes located near the nerve fibers. Simulation results revealed that i-<inline-formula> <tex-math notation="LaTeX">$A\delta $ </tex-math></inline-formula> presented the highest <inline-formula> <tex-math notation="LaTeX">$C$ </tex-math></inline-formula>-selectivity, which provides a basis for non-invasive effective chronic-pain relief.

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