Blocking sympathetic function, whether by surgical sympathectomy, systemic phentol- amine, or systemic guanethidine, relieves partial nerve injury-induced neuropathic pain in laboratory animal models as well as humans (8, 35, 146, 239, 278). Indeed, sympathectomy does not just relieve pathological pain in the body region ipsilateral to the CRPS-initiating event; rather, it also relieves pain arising from anatomically impossible mirror-image sites, that is, the identical body region contralateral to the initiating event (278). Thus sympathetectomy must somehow quiet the contralateral spread of spinal cord hyperexcitability underlying mirror- image pain.
Alterations in sympathetic fibers rapidly follow pe- ripheral nerve injury. This occurs as sprouting of sympa- thetic fibers, creating aberrant communication pathways from the new sympathetic terminals to sensory neurons (35). Sympathetic sprouting has been documented in the region of peripheral terminal fields of sensory neurons (262), at the site of nerve trauma (57), and within the dorsal root ganglia (DRG) containing cell bodies of sen- sory neurons (248, 343). Each of these sites develops spontaneous activity and sensitivity for catecholamines and sympathetic activation (8, 53).
The clearest evidence that immune activation partic- ipates in sympathetic sprouting comes from studies of the DRG. DRG cells receive signals that peripheral nerve injury has occurred via retrograde axonal transport from the trauma site. These retrogradely transported signals trigger sympathetic nerve sprouting into DRG (205, 308). As a result of nerve damage-induced retrogradely trans- ported signals, glial cells within the DRG (called satellite cells) proliferate (248) and become activated (343); mac- rophages are recruited to the DRG as well (63, 176). In turn, the activated satellite glial cells (and, presumably, the macrophages) release proinflammatory cytokines and a variety of growth factors into the extracellular fluid of the DRG (206, 246–248, 258, 277, 308, 358). These sub- stances stimulate and direct the growth of sympathetic fibers, which form basket-like terminals around the satel- lite cells that, in turn, surround neuronal cell bodies (247, 248, 343). For discussion of satellite cell functions, see section IIIA.
LINDA R. WATKINS AND STEVEN F. MAIER
Department of Psychology and the Center for Neuroscience, University of Colorado at Boulder, Boulder, Colorado
Physiol Rev
82: 981–1011, 2002; 10.1152/physrev.00011.2002.
