Porth's Essentials of Pathophysiology, 4e

871

Somatosensory Function, Pain, and Headache

C h a p t e r 3 5

Complex Regional Pain Syndrome The complex regional pain syndrome (CRPS), formerly known as reflex sympathetic dystrophy (RSD), is a rare disorder of the extremities characterized by autonomic and vasomotor instability. 36–38 There are two forms of the CRPS: CRPS I (equivalent of RSD) and CRPS II, also known as causalgia. The International Association for the Study of Pain (IASP) lists the diagnostic criteria for CRPS I as the presence of an initiating traumatic event, continuing pain, allodynia (perception of pain from a nonpainful stimulus), or hyperalgesia dispro- portionate to the inciting event with evidence at some time of edema, changes in skin blood flow, or abnormal sensorimotor activity in the area of pain. The diagno- sis is excluded by the existence of any condition that would otherwise account for the degree of pain and dysfunction. 39 According to the IASP, CRPS II (i.e., causalgia) is diagnosed as the presence of continuing pain, allodynia, or hyperalgesia after a nerve injury, not necessarily lim- ited to the distribution of the injured nerve, with evi- dence at some time of edema, changes in skin blood flow, or abnormal sensorimotor activity in the region of pain. The diagnosis is excluded by the existence of any condition that would otherwise account for the degree of pain and dysfunction. The primary difference between type I and type II is the identification of a defin- able nerve injury. The hallmark of both types of CRPS is pain and mobility problems more severe than the injury warrants. Characteristically, the pain is severe and burning with or without deep aching. Usually, the pain can be elic- ited with the slightest movement or touch to the affected area, it increases with repetitive stimulation, and it lasts even after the stimulation has stopped. The pain can be exacerbated by emotional upsets or any increased peripheral sympathetic nerve stimulation. All the varia- tions of CRPS include sympathetic components. These are characterized by vascular and trophic (e.g., dystro- phic or atrophic) changes to the skin, soft tissue, and bone, and can include rubor or pallor, sweating or dry- ness, edema (often sharply demarcated), and, with time, patchy osteoporosis. The pathophysiologic process of CRPS remains uncertain. Although abnormalities in sympathetic activ- ity are observed, recent experimental data suggest that sensitization of small-diameter, polymodal C and A δ fibers to noxious stimuli may be the basis for hyperalgia to heat and nociceptive stimuli. 38 There is also evidence that central mechanisms may play a role in sensitization of central neurons that occurs after intense peripheral mechanical stimuli or continuous activity in nocicep- tors. The sympathetic nervous system, either directly or indirectly through prostaglandin or α 1 -adrenergic recep- tor activity, is considered to contribute to the excitation and sensitization of the nociceptive afferents. Other proposed mechanisms include neurogenic inflammation caused by the activation of neuromediators, such as sub- stance P, calcitonin gene–related peptide, and histamine, which also mediates inflammation and vasodilation of

microvessels. 36 Recent research demonstrated the pres- ence of autoantibodies against autonomic nervous sys- tem structures in patients with CRPS, especially CRPS II, suggesting that the disorder may result from dys- function of the autonomic nervous system caused by an autoimmune attack. 39 Early mobilization after injury or surgery reduces the likelihood of developing the syndrome. 38 In addition to addressing the underlying disorder, treatment is directed at restoration of function. Physical therapy is a corner- stone of therapy. Pain management involves the use of standard pharmacologic agents used in the manage- ment of neuropathic pain, namely, antidepressants (e.g., amitriptyline) and antiseizure drugs (e.g., gabapen- tin). Short-term corticosteroid (prednisone) treatment may be used in resistant cases. If this does not lead to improvement, treatment by sympathetic blockade may be used to provide pain relief and determine the extent to which the pain is sympathetically maintained. The lat- ter mechanism, when present, might respond to the use of a α 1 -adrenergic receptor antagonist (e.g., terazosin, phenoxybenzamine). Electrical neurostimulation of the spinal cord may also be considered. Neurostimulation not only may provide analgesia, but also may reduce the burning dysesthesia of which many patients complain. It may also improve circulation in the affected extremity by blocking the sympathetic efferent pathways. 38 Phantom Limb Pain Phantom limb pain, a type of neurologic pain, follows amputation of a limb or part of a limb. 40 Pain associated with the loss of a limb can fall into three categories: phantom limb pain, residual limb pain, and phantom limb sensations. It is estimated that up to 95% of all patients who have some form of limb loss will experi- ence sensations in one of these categories. 40 The pain often begins as sensations of tingling, heat and cold, or heaviness, followed by burning, cramping, or shoot- ing pain. It may disappear spontaneously or persist for many years and typically occurs within the first 6 months after the limb loss occurs. 40 One of the more troublesome aspects of phantom limb pain is that the person may experience painful sensations that were present before the amputation, such as that of a painful ulcer or bunion. Several theories have been proposed as to the causes of phantom limb pain. 40 One theory is that the end of a regenerating nerve becomes trapped in the scar tissue of the amputation site. It is known that when a peripheral nerve is cut, the scar tissue that forms becomes a bar- rier to regenerating outgrowth of the axon, which often becomes trapped, forming a tangled growth (i.e., neu- roma) of small-diameter axons, including nociceptive afferents and sympathetic efferents. It has been proposed that the afferents show increased sensitivity to innocu- ous mechanical stimuli and to sympathetic activity and circulating catecholamines. A related theory proposes that the source of phantom limb pain is in the spinal cord, suggesting that the pain is due to the spontaneous firing of spinal cord neurons that have lost their normal