James N. Campbell

Hyperalgesia and sensitization of primary afferent fibers

Publisher Summary This chapter focuses on studies of hyperalgesia following cutaneous injury. Hyperalgesia is a common manifestation of inflammation. It may manifest as pain in the absence of external stimuli—spontaneous pain, as pain that results from low-intensity ordinarily innocuous stimuli—allodynia, and as increased pain to noxious stimuli—injurious or potentially injurious. Information regarding the stimulus is signaled to the central nervous system by highly specialized types of sensory fibers. Cutaneous nociceptive afferent fibers can be unmyelinated (C fiber) or myelinated (A fiber). Sensitization of nociceptors is one neurophysiological correlate of hyperalgesia and is characterized by a decrease in threshold, an increased response to suprathreshold stimuli and, occasionally, by spontaneous activity. The endogenous chemicals that may play a part in hyperalgesia can be broadly subclassified into neurogenic and non-neurogenic. A variety of substances are released from such non-neural tissues as mast cells and vasculature, following injury. Hyperalgesia to mechanical stimuli may indicate certain chronic pain syndromes such as causalgia and reflex sympathetic dystrophy, as well as postherpetic neuralgia and metabolic neuropathies.

Plasticity of the Neural Events Related to Pain

A discussion of pain is apropos to a symposium that honors the career of Vernon Mountcastle. Professor Mountcastle served at one time as a mentor for us and has had a substantial influence on our research on pain sensibility. Though there are many aspects of Mountcastle’s influence that would be difficult to set down in specific terms, three themes stand out.

Mecanismos periféricos de la nocicepción cutánea

Los nociceptores son una clase especializada de aferentes primarios que responden a estimulos intensos, nocivos. Los nociceptores amielinicos transmiten el dolor urente por estimulos caloricos intensos aplicados sobre la piel lampina de la mano y tambien el dolor por presion sostenida. Los nociceptores mielinicos transmiten el dolor agudo por estimulos caloricos aplicados sobre la piel hirsuta y por estimulos mecanicos intensos. Los nociceptores mielinicos y amielinicos transmiten el dolor por estimulos quimicos. Despues de una lesion cutanea, aumenta el dolor en respuesta a estimulos cutaneos, denominado hiperalgesia, en el lugar de la lesion (hiperalgesia primaria) y en la piel lesionada circundante (hiperalgesia secundaria). La lesion tisular aumenta la respuesta de los nociceptores, denominada sensibilizacion, que representa la hiperalgesia primaria. Esta sensibilizacion se debe a la liberacion local de mediadores inflamatorios. La hiperalgesia secundaria se debe a la sensibilizacion de neuronas del sistema nervioso central. Cuando los nervios son seccionados, los nociceptores lesionados desarrollan una actividad espontanea y una sensibilidad mecanica, calorica y quimica ectopica. Tambien cambian las propiedades de los nociceptores proximos, no afectados. Tanto los nociceptores lesionados como los no lesionados pueden desarrollar una respuesta a agentes adrenergicos, que pueden explicar la afectacion del sistema nervioso simpatico en ciertas formas de dolor neuropatico.