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Pain. 2014 Jul;155(7):1384-91. doi: 10.1016/j.pain.2014.04.018. Epub 2014 Apr 21.

Peripheral nervous system origin of phantom limb pain.

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Pain and Rehabilitation Clinic, National Trauma Center, Trauma University Hospital and Galenus Clinic, Tirana, Albania.
Pain Rehabilitation Unit, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel.
Biomedical and Experimental Department, Faculty of Medicine, University of Medicine, Tirana, Albania.
Department of Cell and Developmental Biology, Institute of Life Sciences and Center for Research on Pain, The Hebrew University of Jerusalem, Jerusalem 91904, Israel. Electronic address:


Nearly all amputees continue to feel their missing limb as if it still existed, and many experience chronic phantom limb pain (PLP). What is the origin of these sensations? There is currently a broad consensus among investigators that PLP is a top-down phenomenon, triggered by loss of sensory input and caused by maladaptive cortical plasticity. We tested the alternative hypothesis that PLP is primarily a bottom-up process, due not to the loss of input but rather to exaggerated input, generated ectopically in axotomized primary afferent neurons in the dorsal root ganglia (DRGs) that used to innervate the limb. In 31 amputees, the local anesthetic lidocaine was applied intrathecally and/or to the DRG surface (intraforaminal epidural block). This rapidly and reversibly extinguished PLP and also nonpainful phantom limb sensation (npPLS). Control injections were ineffective. For intraforaminal block, the effect was topographically appropriate. The suppression of PLP and npPLS could also be demonstrated using dilute lidocaine concentrations that are sufficient to suppress DRG ectopia but not to block the propagation of impulses generated further distally in the nerve. PLP is driven primarily by activity generated within the DRG. We recommend the DRG as a target for treatment of PLP and perhaps also other types of regional neuropathic pain.


DRG; Ectopic firing; Electrogenesis; Intraforaminal; Neuropathic pain; Phantom limb pain

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