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Ever since Claude Bernard implicated the sympathetic nervous system in sensation, its role in nociception has been the subject of debate.1 No one would argue with the fact that the sympathetic nervous system is intimately involved with the preservation of homeostasis and noxious challenges in humans, although the manner in which it influences the sensation of pain has, until recently, escaped explanation.2 Anatomically, the sympathetic nervous system constitutes a highly complex arrangement of preganglionic and postganglionic neurons that subserve specific and diverse functions of target organs, including enteric neurons, smooth muscle, syncytial muscle, and striated muscle.3 Physiologically, the sympathetic nervous system is associated in some way with both systemic and specific local reactions, which are expressed by supratentorial and confrontational aspects that are represented in the periaquaductal gray matter of the midbrain (e.g., non-opioid analgesia).4,5 In contrast, rest and quiescence are represented in the ventrolateral periaquaductal gray matter, being associated with endogenous opioid analgesia.


The stress response described by Selye,6 “fight or flight,” involves both spinal levels of integration, with hypothalamo-mesencephalic centers, but is associated with adrenocortical and hypothalamo-hypophyseal responses designed to protect the organism under normal biologic conditions. A secondary set of responses to sympathetic activity that can be considered pathophysiologic and occur with or without obvious nerve injury are those changes in blood flow, sudomotor and muscle activity, with subsequent trophic changes and abnormal sensation long after the noxious event.7,8 Sensory changes include allodynia, hypoalgesia, hyperalgesia, hyperesthesia, and hyperpathia. Why, and in what manner, the sympathetic nervous system is involved in these changes that occur in a small but readily identifiable group of patients is still unclear. However, recent research has clarified some of the previous misconceptions with regard to levels of sympathetic activity, involvement of the central nervous system, and the possibility of preexisting immunologic factors. Interestingly, similarities in the characteristics of complex regional pain syndrome (CRPS) are seen in other chronic pain states, such as irritable bowel syndrome, interstitial cystitis, nonulcer dyspepsia, and certain cases of angina pectoris.


During the Civil War, Weir Mitchell9 drew attention to the exaggerated response to nerve injury that was distinct from the neurogenic inflammation that is associated with most nerve injuries. These patients typically suffered from a penetrating injury in the vicinity of a major nerve, in most cases without disruption, and typically caused by a musket shot. Mitchell called this causalgia because of the bizarre swelling, heat (causa), and pain (algia), which were out of all proportion to the signs and symptoms of most nerve injuries. Leriche,10 a French surgeon, also described similar syndromes in the lower extremities for which he developed the surgical procedure of stripping the sympathetic nervous plexus from the large vessels in the lower extremities. Sudeck, in a series of articles, provided similar descriptions with detailed observations of the bony and trophic changes following injury that came to be described ...

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