Experimental realization of a signal transduction algorithm

A theory of signal transduction specifies that in biological systems, any instantaneous input is appreciated by its departure from the mean past activity that occurred over a certain time window called the sample period; it also specifies that any input generates two so-called first- and second-order effects that are opposite in sign. We here report the detailed experimental realization of the algorithm that formalizes this signal transduction process; numerical simulations adequately predicted various intricate features of the (first order) analgesia and the paradoxical (second order) hyperalgesia which morphine produces. The data also offer a first estimation of the physiological sample period that may govern the classical rat tail flick response. The signal transduction process appears to operate ubiquitously and provides an unprecedented account of the paradoxical effects that have been observed with different signalling systems. This process may also operate with such phenomena as refractoriness, homeostasis, adaptation, sensitization, dependence, tolerance or resistance and neuronal plasticity. (C) 1999 Academic Press.