TY - JOUR
T1 - Neuronal loss in the rostral ventromedial medulla in a rat model of neuropathic pain
AU - Lan Leong, Mai
AU - Gu, Ming
AU - Speltz-Paiz, Rebecca
AU - Stahura, Eleanor I.
AU - Mottey, Neli
AU - Steer, Clifford J.
AU - Wessendorf, Martin
PY - 2011/11/23
Y1 - 2011/11/23
N2 - Cell death has been reported in the CNS in models of neuropathic pain (Sugimoto et al., 1990; Whiteside and Munglani, 2001; Scholz et al., 2005; Fuccio et al., 2009). In our present study, we examined the effects of spinal nerve ligation (SNL) on the number of neurons in the rostral ventromedial medulla (RVM), a brainstem region involved in modulation of nociception. In rats receiving SNL, we found that the number of RVM neurons decreased by 23% in the side ipsilateral to the surgery. The loss of RVM neurons was also associated with a bilateral increase in the number of glia as well as bilateral activation of both astrocytes and microglia. Administration of tauroursodeoxycholic acid (TUDCA), which reportedly inhibits apoptosis, significantly reduced the loss of neurons, the increase in glia, and the mechanical hypersensitivity induced by SNL. Among RVM neurons, we found that serotonergic (5-hydroxytryptamine, 5-HT) neurons decreased by 35% ipsilateral to SNL. Consistent with these findings, the density of 5-HT-immunoreactive varicosities in the superficial dorsal horn of the spinal cord was 15-30% lower, ipsilateral to SNL. To test the function of the remaining 5-HT neurons, we administered the 5-HT neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT). Interestingly, after 5,7-DHT, mechanical withdrawal thresholds increased significantly. We conclude that nerve injury induces death of antinociceptiveRVMneurons that can be reduced or abolished by TUDCA. We propose that the loss of RVM neurons shifts the balance of descending control from pain inhibition to pain facilitation.
AB - Cell death has been reported in the CNS in models of neuropathic pain (Sugimoto et al., 1990; Whiteside and Munglani, 2001; Scholz et al., 2005; Fuccio et al., 2009). In our present study, we examined the effects of spinal nerve ligation (SNL) on the number of neurons in the rostral ventromedial medulla (RVM), a brainstem region involved in modulation of nociception. In rats receiving SNL, we found that the number of RVM neurons decreased by 23% in the side ipsilateral to the surgery. The loss of RVM neurons was also associated with a bilateral increase in the number of glia as well as bilateral activation of both astrocytes and microglia. Administration of tauroursodeoxycholic acid (TUDCA), which reportedly inhibits apoptosis, significantly reduced the loss of neurons, the increase in glia, and the mechanical hypersensitivity induced by SNL. Among RVM neurons, we found that serotonergic (5-hydroxytryptamine, 5-HT) neurons decreased by 35% ipsilateral to SNL. Consistent with these findings, the density of 5-HT-immunoreactive varicosities in the superficial dorsal horn of the spinal cord was 15-30% lower, ipsilateral to SNL. To test the function of the remaining 5-HT neurons, we administered the 5-HT neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT). Interestingly, after 5,7-DHT, mechanical withdrawal thresholds increased significantly. We conclude that nerve injury induces death of antinociceptiveRVMneurons that can be reduced or abolished by TUDCA. We propose that the loss of RVM neurons shifts the balance of descending control from pain inhibition to pain facilitation.
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U2 - 10.1523/JNEUROSCI.1268-11.2011
DO - 10.1523/JNEUROSCI.1268-11.2011
M3 - Article
C2 - 22114272
AN - SCOPUS:81855180513
SN - 0270-6474
VL - 31
SP - 17028
EP - 17039
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 47
ER -