There is abundant clinical evidence that depression occurs with high frequency among chronic pain patients. When compared with other serious medical disorders, the prevalence of depression in chronic pain appears high. The fundamental reason for this association is unknown. Theories have attempted to explain the link between pain and depression in terms of psychologic mechanisms. Other theories highlight shared neurobiologic substrates. However, a comprehensive theory integrating biologic and psychologic viewpoints remains elusive. In this article, we draw on research on neuroplastic processes in corticolimbic structures to model the linkage between the sensory and affective domains of pain. Our hypothesis is based on kindling experiments in animals that elucidate the complex neurobiologic mechanisms that transduce exteroceptive and interoceptive stimuli into "memory" at the cellular/synaptic level. This experimental model has found application in the affective disorders to explain how a person's history of exposure to psychologic trauma configures the neurobiologic substrate for later-amplified pathologic response. In applying kindling research to pain, we begin by reviewing the literature on nociception-induced neuroplasticity at the corticolimbic level. We suggest that kindling and related models of neuroplasticity can be used to describe ways in which exposure to a noxious stimulus may, under certain conditions, lead to a sensitized corticolimbic state. This sensitized state can be described in terms of the kindling properties of amplification, spontaneity, neuroanatomic spreading, and cross-sensitization. A case example illustrates how these properties offer a neurobiologic framework for understanding the sensory/affective/behavioral symptom complex seen in a subset of chronic pain patients. These patients are characterized by atypical and treatment-refractory pain complaints, in association with disturbances of mood, sleep, energy, libido, memory/concentration, behavior, and stress intolerance. We introduce the term "limbically augmented pain syndrome" to describe this symptom complex.
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