Changes in GAD- and GABA- immunoreactivity in the spinal dorsal horn after peripheral nerve injury and promotion of recovery by lumbar transplant of immortalized serotonergic precursors

Blocking Caspase Activity Prevents Transsynaptic Neuronal Apoptosis and the Loss of Inhibition in Lamina II of the Dorsal Horn after Peripheral Nerve Injury

“…The total GAD67 protein level in the dorsal horn remains stable after SNI (Moore et al, 2002), implying that surviving interneurons increase the synthesis of GAD67. There are conflicting reports on changes in GABA-immunoreactive cells after peripheral nerve injury, which likely reflect the different timings of nerve lesions, the spinal cord segments analyzed, and the variability of this immunohistochemical technique (Ibuki et al, 1997;Eaton et al, 1998;Polgar et al, 2003). We found that the proportion of lost GABAergic interneurons equals the decline of total neurons, arguing against a selective vulnerability of these interneurons to nerve injury-induced degeneration.…”

“…In situ markers of apoptosis, such as TUNEL, are positive for a very short time, only 1-3 h (Gavrieli et al, 1992;Rossiter et al, 1996). Using assumption-based profile counts to estimate the number of surviving neurons (Ibuki et al, 1997;Eaton et al, 1998;de Novellis et al, 2004) is also inappropriate: a quantitative evaluation of neuronal loss requires stereological counting techniques (West, 1999). Therefore, we used a physical dissector method to determine the decrease in dorsal horn neurons 4 weeks after SNI.…”

Amelioration of chronic neuropathic pain after partial nerve injury by adeno-associated viral (AAV) vector-mediated over-expression of BDNF in the rat spinal cord

“…Transplants of BDNF-secreting cells in the subarachnoid space after nerve injury has been shown to restore the endogenous GABA system within 1 week after grafting. 35 Infusion of BDNF into the midbrain has a significant antinociceptive effect with accompanying enhanced serotonergic activity in the brain and spinal cord. 33 Delivery of the BDNF gene by AAV-mediated gene transfer, and increased spinal BDNF levels, related to BDNF gene over-expression which supply BDNF to the pain pathways in the dorsal spinal cord could prove to have therapeutic value.…”

Loss of Neurons from Laminas I-III of the Spinal Dorsal Horn Is Not Required for Development of Tactile Allodynia in the Spared Nerve Injury Model of Neuropathic Pain

“…Evidence for this hypothesis includes the following observations: (1) loss of GABAergic or glycinergic inhibition within the dorsal horn leads to allodynia (Yaksh, 1989) and a lowered threshold for withdrawal reflexes (Sivilotti and Woolf, 1994); (2) there is a reduction in the level of GABA (Castro-Lopes et al, 1993;Ibuki et al, 1997;Eaton et al, 1998) and its synthesizing enzyme glutamate decarboxylase (Moore et al, 2002) in the ipsilateral dorsal horn after nerve injury; (3) "dark neurons" (Sugimoto et al, 1990) and apoptotic cells labeled with the terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) method (Kawamura et al, 1997;Azkue et al, 1998;Whiteside and Munglani, 2001;Moore et al, 2002;de Novellis et al, 2004) have been detected in the dorsal horn after various types of nerve injury; (4) a substantial reduction of primary afferent-evoked IPSCs in lamina II neurons has been reported in neuropathic models (but not after sciatic nerve transection) and was thought to result from a presynaptic mechanism involving reduction of GABA release (Moore et al, 2002). Although most studies of apoptosis in the dorsal horn after nerve injury have not identified the cell types involved, Moore et al (2002) reported that in the spared nerve injury (SNI) model (Decosterd and Woolf, 2000), ϳ10% of TUNEL-positive cells were neuronal.…”