Surgery Godfather

Chapter 2187: Chapter 1434: Crossing the River by Feeling for Stones

The results of the cotton test took everyone by surprise.

Fritz started with a cotton ball at M7’s dorsum of the foot, moving upwards bit by bit. A high-speed camera recorded at a thousand frames per second, capturing even the slightest muscle twitches that are invisible to the naked eye, freezing them in slow-motion frames.

"Dorsum of the foot, no response," Eva stared at the real-time playback screen, "ankle, no response. Calf... hold on, stop."

She pressed the pause button, rewound the video by three frames, and zoomed in to the pixel level.

A barely visible ripple appeared on the skin of M7’s mid-calf, not a muscle contraction, but a tremor of the skin itself, like the tiniest ripples when the wind blows over a lake. Fritz’s cotton ball had just brushed over there, with a force so light it was almost immeasurable.

"This is a tactile response," Eva’s voice was slightly tense, "Aβ fibers mediate light touch, with an extremely low threshold. The light touch threshold for normal primates is between 0.5 to 1 gram-force, this stimulus just now was estimated to be less than 0.2 gram-force."

"What does that indicate?" Yang Ping asked.

"It indicates two things," Eva pulled out the previous pain threshold data, "First, M7’s sensory pathways are indeed recovering, and the order of recovery matches theoretical predictions—pain recovers first, then light touch, and finally proprioception. Second, its tactile threshold is lower than normal, indicating possible tactile hypersensitivity, the same mechanism as the previous pain hypersensitivity—central sensitization."

Weber came over, looking at the barely visible ripple on the screen.

"Central sensitization," he repeated the term, "one of the most common complications after spinal cord injury. It’s not that the patient doesn’t feel, but feels too much. Normal touch becomes pain, normal temperature becomes burning."

"Right," Yang Ping nodded, "Moreover, once central sensitization forms, it’s hard to reverse. It involves synaptic plasticity changes in spinal dorsal horn neurons, NMDA receptor activation, calcium ion influx, followed by a series of cascading reactions, MAPK pathway, CREB phosphorylation, gene expression changes. It’s a positive feedback loop, the more sensitized, the more excited; the more excited, the more sensitized."

"So we face a paradox," Manstein frowned, "The original cell activation strategy promotes nerve regeneration, but the regenerated nerves may carry ’wrong signals’, leading to central sensitization. We cured the paralysis but potentially created a patient in pain."

The Meeting Room fell silent again.

"No," Yang Ping suddenly said, "it’s not a paradox, it’s a matter of time window."

He went to the whiteboard and drew a timeline.

"The formation of central sensitization requires two conditions: first, abnormal neural inflow, with residual or regenerated nerve fibers discharging abnormally after injury; second, plastic changes in spinal dorsal horn neurons, increased synaptic strength, decreased function of inhibitory interneurons. Both conditions require time."

He marked two points on the timeline: "Post-operative third week, pain recovery marks the first phase of abnormal inflow; post-operative fourth week, tactile recovery. If left unchecked, central sensitization will solidify in two to three weeks."

"But now we know," his pen tip pointed to the fourth-week mark, "we can intervene within this time window to prevent the solidification of sensitization."

"How to intervene?" Tang Shun asked.

"Two approaches," Yang Ping put down the pen, "First, reduce abnormal inflow. For example, using sodium channel blockers to inhibit ectopic discharge of injured nerve fibers. But sodium channel blockers would affect normal nerve conduction, potentially offsetting our recovery effect."

"What’s the second method?"

"Enhance inhibitory regulation," Yang Ping continued, "The spinal dorsal horn has a large number of inhibitory interneurons, mainly GABAergic and glycinergic. A key mechanism of central sensitization is the decline in function of these inhibitory neurons. If we can enhance their activity, we can block the positive feedback loop of sensitization without affecting normal inflow."

"GABA receptor agonists?" Weber asked.

"Yes, but not just simple agonists. The GABA_A receptor is a chloride channel; continuous activation leads to receptor desensitization, making the effect less and less. What we need is an ’intelligent’ regulation strategy that enhances inhibition only during abnormal excitation and does not interfere during normal activity."

"That sounds like..." Lina adjusted her glasses.

"Closed-loop neural control," Eva took over the conversation, "the same concept as my biosensor. Real-time monitoring of electrical activity in the spinal dorsal horn, automatically releasing GABAergic agonists when abnormal high-frequency discharges are detected; not releasing them during normal discharges."

"But how to locally release GABAergic agonists?" Hans frowned, "Administering systemically will cross the blood-brain barrier, causing sedation and cognitive impairment. Local administration requires an implanted pump, which carries a high risk of infection."

"No need for exogenous drugs," Yang Ping shook his head, "we can use optogenetics."

"Optogenetics?" Manstein widened his eyes, "On primates?"

"Yes," Yang Ping nodded, "A team conducted optogenetic experiments on the visual cortex of Heng River Monkeys in 2016, proving safety and feasibility. Our plan is: using viral vectors to introduce light-sensitive ion channels, such as NpHR, a chloride ion pump, into the inhibitory interneurons of M7’s spinal dorsal horn. Then use implanted optical fibers to emit yellow light to activate NpHR when abnormal electrical activity is detected, enhancing local inhibition."

"This is way too advanced," Tang Shun gasped, "viral vectors, optogenetics, closed-loop control, any issue with these combined technologies could be disastrous."

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