A general theory on pain as an integrated thermodynamic mechanism

Abstract

The phenomenological concepts to describe pain as a primarily unidirectional warning mechanism for the existence of specific noxae appear to be insufficient. Here we present a theory and a model according to which pain can be represented as an integrated mechanism of local cell energy homeostasis. It postulates the occurrence of a pain sensation in case of a relative deficit of the intracellular metabolic power balance in tissues. In that connection, power deficits are primarily seen in a relative dysfunction of the mitochondrial respiratory chain phosphorylation. Through a resulting reduced activity of ATP-dependent ion pumps and ion channels, there occurs an extracellular ion shifting in the interstitial space. This changes, according to the Hodgkin-Huxley model, the conditions of the membrane potential of regionally competent terminal afferent nerve fibers. The neuronal excitability pattern modulated therefrom is demodulated as pain signal in the CNS. This signal may lead there, as a closed-loop mechanism, to a negative feedback activation in order to counterbalance the deficit of the peripheral power balance. The origin of a pain is represented as a disturbed energy cycle efficiency of an impaired cell. Operatively the phenomenon results from a mechanism that couples the current status of the intracellular energetic power balance to neuronal excitation. In this mechanism the pain phenomenon per se represents an implied signal only that indicates various parameters of a power balance deficit. The implicit functional relation of pain to the energy deficit can be summarised as P=f(-DeltaQ(o)). Projections and clinical implications are discussed.