Dermatomal Scratching After Intramedullary Quisqualate Injection: Correlation With Cutaneous Denervation

Abstract

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. Perspective 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.

Longitudinal measurements of syrinx size in a rat model of posttraumatic syringomyelia

“…6 All experimental animals developed a syrinx (syrinx animals). No control animals developed a syrinx or spinal cord edema.…”

Sensory Stimulation Prior to Spinal Cord Injury Induces Post-Injury Dysesthesia in Mice

“…A second explanation for the site and cause of OG in this study is that the pre-injury sensory stimuli induced a peripheral irritation (Brewer et al, 2008) that was exacerbated by SCI. Indeed, the proportion of subjects that exhibited OG increased with the intensity of the pre-injury stimulation.…”

“…One possible indication of spontaneous pain or dysesthesia in animal models is self-directed overgrooming (OG) or ''excessive grooming'' behavior, including scratching, licking, and=or biting (Brewer et al, 2008;Kerr et al, 2007;Yezierski et al, 1998;Zhang et al, 2001;reviewed in Kauppila, 1998). Overgrooming after SCI has been described thoroughly in lesion models induced by focal excitotoxicity (Yezierski et al, 1998).…”

Common Neuropathic Itch Syndromes

“…The severe truncal dermatomal scratching that these rats develop was formerly interpreted as modeling neuropathic pain, but we suggested it better modeled intramedullary itch. Study of cutaneous innervation in these rats revealed profound deafferentation in their itchy skin, implying that the small spinal-cord injections cause retrograde degeneration of primary afferent (peripheral) sensory neurons as well as of intrinsic spinal neurons (15). Thus intramedullary itch may not be purely central.…”

“…Murine knock-out studies ofthe atonal-related transcription factor Bhlhb5 have identified dorsal-horn inhibitory intemeurons that tonically inhibit itch signals (13). Spinal cord lesions that perturb this circuitry can cause neuropathic itch in humans and rodent models, as discussed below (14,15). Much less is known about central than peripheral itch pathways.…”