A Functional, Cellular, and Evolutionary Model of Nociceptive Plasticity in Aplysia

Nociceptive plasticity is defined as behavioral and cellular modification produced by activation of nociceptors. A brief survey of nociceptive plasticity in Aplysia reveals a puzzling mixture of behavioral modifications of opposite sign and widely varying durations. These include general sensitization, site-specific sensitization, response-specific facilitation, and inhibition of defensive responses. This behavioral complexity is more than matched by the complexity of cellular correlates reported for the behavioral modifications. A functional model is proposed linking complex patterns of behavioral and neural plasticity in Aplysia to potentially general principles of nociceptive function. This model is centered around three overlapping but functionally distinct phases: injury detection, escape, and recuperation. A hypothesis about the early origin of nociceptive plasticity in primitive mechanosensory neurons is then developed, based on similarities in the organization and modifiability of nociceptive systems in evolutionarily divergent groups (primarily mollusks and mammals) and on inferences about the early adaptiveness of postinjury behavioral plasticity. Preliminary evidence suggests that aspects of nociceptive plasticity, and perhaps other forms of memory, may have been derived from cellular repair and signal compensation mechanisms.