Physiology and pharmacology of the postinjury pain state

Abstract

CUTE ACTIVATION of small sensory afferent axons evokes autonomic responses and pain behavior in humans and animals. This effect is mediated by the activation of spinofugal projection neurons. These projection systems traveling both ipsilaterally and contralaterally in the ventrolateral aspect of the spinal cord, projeering supraspinally into the medulla, mesencephalon, and diencephalon. Medullary projections serVe to activate spino-bulbo-spinal reflexes that influence autonomic tone. Other projections into the mesencephalon and thalamus are assumed to contribute to the perceptual and complex emotive and discriminative components of the pain state. Thus, the somatotopie association between spinal segment and supraspinal projections to the ventrobasal thalamus, which itself sends projections to the sensory cortex, has been well described. The mapping of the sensory homunculus by the hard-wired projections is believed to serve in establishing the precise localization of the stimulus event in the uninjured nervous system. More recently, work with positron emission tomography has indicated that areas in the anterior cingulate cortex known to receive input from several thalamic nuclei, notably the nucleus submedius, may be activated in the presence of noxious, but not nonnoxious sensory input. 2 Importantly, the submedius is itself the recipient of nociceptive-specific input. Details of these ascending systems are discussed in detail elsewhere) '4 However, it is important to appreciate that the encoding by the sensory afferent and the spinal dorsal horn of the nociceptive stimulus is the first step in nociceptive processing, and the properties of this encoding process contribute properties that are important for the understanding of the behavioral correlates of nociception. In this article, we consider aspects of the mechanisms whereby tissue injury leads to an ongoing pain state from the perspective of the organization of the sensory afferents and the spinal dorsal horn.