|Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥2,600,000 (Direct Cost: ¥2,600,000)
Background : Spinal cord injury(SCI) results in chronic central neuropathic pain in dermatomes caudal to the lesion(below-level pain) and rostral to the lesion(above-level pain), which has remained refractory to clinical, treatment despite the development of various therapeutic strategies. In order to gain a better understanding of the pain, we investigated changes in physiological and pharmacological properties of spinal dorsal horn neurons in spinal segments rostral and caudal to the lesion in rats with SCI.
Methods : The right spinal cord of Sprague-Dawley rats was hemisected at the level of L2. At 10 to 14 days after the SCI, when mechanical hyperalgesia/allodynia had fully developed, spontaneous activity and evoked responses to non-noxious and noxious mechanical stimuli of wide-dynamic-range(WDR) and high-threshold(HT) neurons rostral and caudal to the lesion were recorded. Cumulative doses of morphine were administered systemically(0.1-3mg/kg) and spinally(0.1-5μg), and spontaneou
s activity and evoked responses to the stimuli of the neurons were evaluated.
Results : Spontaneous activity significantly increased in WDR neurons both rostral and caudal to the SCI site, but high-frequency background discharges with burst patterns were observed only in neurons rostral to the SCI site. After the SCI, which involved cutting the L2 dorsal root and hemisectioning the spinal cord, WDR and HT neurons rostral to the SCI site still had receptive fields on the skin of the hindpaw, dermatomes L3,L4 and L5. Significant increases in responses to the mechanical stimuli were seen both in WDR and HT neurons located both rostrally and caudally to the lesion. The responses to non-noxious and noxious stimuli were significantly greater in WDR neurons caudal to the SCI site than those in WDR neurons rostral to the SCI site. In contrast, the responses to noxious stimuli were significantly higher in HT neurons rostral to the SCI site than those in HT neurons caudal to the SCI site. Systemically administered morphine had a greater effect on responses to non-noxious and noxious stimuli of WDR neurons rostral to the SCI site than those caudal to the SCI site. Spinally administered morphine significantly suppressed responses of WDR neurons in SCI animals to non-noxious stimuli compared to those in sham-operated control animals.
Conclusions : The findings suggest that changes in properties of spinal dorsal horn neurons after SCI are caused by different physiological and pharmacological mechanisms depending on the classification of the neurons and their segmental locations and that different spinal mechanisms contribute to SCI-induced pain. Less