Dermatomal scratching after intramedullary quisqualate injection: correlation with cutaneous denervation.
Central nervous system lesions cause peripheral dysfunctions currently attributed to central cell death that compromises function of intact peripheral nerves. Injecting quisqualate (QUIS) into the rat spinal cord models spinal cord injury (SCI) and causes at-level scratching and self-injury. Such overgrooming was interpreted to model pain until patients with self-injurious scratching after SCI reported itch motivated scratching that was painless because of sensory loss. Because self-injurious scratching is difficult to explain by central mechanisms alone, we hypothesized that QUIS injections damage peripheral axons of at-level afferents. QUIS was injected into thoracic spinal cords of 18 Long-Evans rats. Animals were killed 3 days after overgrooming began or 14 days after injection. Spinal cord lesions were localized and DRG-immunolabeled for ATF-3. At-level and control skin samples were PGP9.5-immunabeled to quantify axons. Eighty-four percent of QUIS rats overgroomed. Skin in these regions had lost two-thirds of epidermal innervation as compared with controls (P < .001). Rats that overgroomed had 47% less axon-length than nongrooming rats (P = .006). The presence of ATF-3 immunolabeled neurons within diagnosis-related groups of QUIS rats indicated death of afferent cell bodies. Overgrooming after QUIS injections may not be due entirely to central changes. As in humans, self-injurious neuropathic scratching appeared to require loss of protective pain sensations in addition to peripheral denervation.


CONCLUSIONS
This study suggests that intramedullary injection of quisqualic acid in rats causes death of at-level peripheral as well as central neurons. Self-injurious dermatomal scratching that develops in spinal-injured rats may reflect neuropathic itch and loss of protective pain sensations.
Brewer
Kori L
KL
Department of Emergency Medicine, Brody School of Medicine at East Carolina University, Greenville, North Carolina 27834, USA. brewerk@ecu.edu
Lee
Jeung Woon
JW
Downs
Heather
H
Oaklander
Anne Louise
AL
Yezierski
Robert P
RP
D051700:Activating Transcription Factor 3 / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D003714:Denervation / Q000009:adverse effects; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D010146:Pain / Q000209:etiology / Q000503:physiopathology*; D011537:Pruritus / Q000209:etiology / Q000503:physiopathology*; D016318:Quisqualic Acid; D051381:Rats; D020318:Rats, Long-Evans; D012867:Skin / Q000294:innervation / Q000503:physiopathology*; D013119:Spinal Cord Injuries / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D013133:Spinothalamic Tracts / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
D051700:Activating Transcription Factor 3; C497108:Atf3 protein, rat; D016318:Quisqualic Acid; C489034:UCHL1 protein, rat; D043222:Ubiquitin Thiolesterase