Fink Wolfgang, Raffa Robert B
Visual and Autonomous Exploration Systems Research Laboratory, University of Arizona, Tucson, AZ, 85721, USA.
Temple University (Emeritus), Tucson, AZ, 85718, USA.
J Pain Res. 2025 Aug 26;18:4373-4385. doi: 10.2147/JPR.S525449. eCollection 2025.
Pain is a subjective experience, the perception of stimulus input transmitted by neurons that respond to real or perceived tissue injury and propagate the information to the brain. Under normal conditions, the perception is a reliable indicator of the magnitude and duration of the sensory input (viz. threat), so that appropriate action can be taken (eg, fight-or-flight). Two pathways have been recognized: "ascending pathways" mediating sensory input→perception and "descending pathways" mediating perception→response. Interactions between the two are increasingly appreciated, ie, ascending signals often modulated by descending ones. Our thesis is that there is an interactive feedback loop that allows pain to be modeled as a control system (with a postulated thermostat-analogous "nocistat") and that such an undertaking could lead to better understanding of pain dynamics, and ultimately to recommendations for better pain treatment.
We here introduce a system-theoretical approach, based on the well-known Lotka-Volterra dynamics, to describe ascending and descending pain pathways as a coupled control and feedback loop. The resulting model is mathematically represented by a system of coupled differential equations with a non-linear interaction term, and poses a pluripotent progression of the Gate Control System Theory to a macroscopic, clinically applicable view of pain and its mitigation through modulation.
We present preliminary, qualitative simulation results for a variety of sensory inputs (ie, pain stimuli) that are inspired by clinical pain conditions. These comprise, but are not limited to, sudden onset of (1) constant pain stimulus; (2) exponentially decaying pain stimulus; (3) linearly decaying pain stimulus; (4) exponentially increasing pain stimulus; and (5) linearly increasing pain stimulus.
The introduced coupled control and feedback loop model is accessible and readily extensible, while mathematically rigorous, to approximate clinical findings more realistically, both qualitatively and quantitatively, the latter taking advantage of the fitting parameters in the model.
疼痛是一种主观体验，是对由神经元传递的刺激输入的感知，这些神经元对实际的或感知到的组织损伤做出反应，并将信息传递到大脑。在正常情况下，这种感知是感觉输入（即威胁）的强度和持续时间的可靠指标，以便能够采取适当的行动（例如，战斗或逃跑）。已经确认了两条通路：介导感觉输入→感知的“上行通路”和介导感知→反应的“下行通路”。人们越来越认识到这两条通路之间的相互作用，即上行信号常常受到下行信号的调节。我们的论点是，存在一个交互式反馈回路，使得疼痛可以被建模为一个控制系统（假设有一个类似恒温器的“伤害抑制器”），并且这样的研究能够更好地理解疼痛动态，最终为更好的疼痛治疗提供建议。
我们在此引入一种基于著名的洛特卡 - 沃尔泰拉动力学的系统理论方法，将上行和下行疼痛通路描述为一个耦合的控制和反馈回路。所得模型由一个带有非线性相互作用项的耦合微分方程组进行数学表示，并且是对门控系统理论的多能扩展，形成了一个关于疼痛及其通过调节缓解的宏观的、临床可应用的观点。
我们展示了受临床疼痛状况启发的各种感觉输入（即疼痛刺激）的初步定性模拟结果。这些包括但不限于以下情况的突然发作：（1）持续疼痛刺激；（2）指数衰减疼痛刺激；（3）线性衰减疼痛刺激；（4）指数增加疼痛刺激；以及（5）线性增加疼痛刺激。
所引入的耦合控制和反馈回路模型易于理解且易于扩展，同时在数学上严谨，能够在定性和定量方面更逼真地逼近临床发现，后者利用了模型中的拟合参数。
