Mathematical and Computational Models for Pain: A Systematic Review

Abstract

Objective: There is no single prevailing theory of pain that explains its origin, qualities, and alleviation. Although many studies have investigated various molecular targets for pain management, few have attempted to examine the etiology or working mechanisms of pain through mathematical or computational model development. In this systematic review, we identified and classified mathematical and computational models for characterizing pain.

Methods: The databases queried were Science Direct and PubMed, yielding 560 articles published prior to January 1st, 2020. After screening for inclusion of mathematical or computational models of pain, 31 articles were deemed relevant.

Results: Most of the reviewed articles utilized classification algorithms to categorize pain and no-pain conditions. We found the literature heavily focused on the application of existing models or machine learning algorithms to identify the presence or absence of pain, rather than to explore features of pain that may be used for diagnostics and treatment.

Conclusions: Although understudied, the development of mathematical models may augment the current understanding of pain by providing directions for testable hypotheses of its underlying mechanisms. Additional focus is needed on developing models that seek to understand the underlying mechanisms of pain, as this could potentially lead to major breakthroughs in its treatment.

Keywords: Computational Biology; Mathematical Model; Pain Mechanism; Pain Model.

Figure 1.

Schematic view of the methodology used for the systematic review. From the filtered search, the articles reviewed were required to contain a mathematical theory or computational approach to characterizing pain.

Figure 2.

Articles sorted according to their classification algorithm, data collection method, or proposal of a mathematical model. Articles could belong to more than one category and subcategory.

Figure 3.

Melzack and Wall’s gate control theory of pain shown schematically. Compare with the original Figure 4 in [19] and the variants in Figure 1 in [15] and Figure 1 in [33]. Plus signs (+) denote excitation, and minus signs (−) denote inhibition. Cognitive control can be excitatory or inhibitory. SG = substantia gelatinosa cells in the dorsal horn of the spinal cord.