Mechanical allodynia following contusion injury of the rat spinal cord is associated with loss of GABAergic inhibition in the dorsal horn

Abstract

The present study investigated whether mechanical allodynia following contusive spinal cord injury (SCI) of the thoracic segments 12 and 13 of the rat was associated with a reduction in gamma-aminobutyric acid (GABA)ergic inhibition adjacent to the site of injury. Five to 7 days following SCI, extracellular recordings were obtained from dorsal horn neurones located 1-2 segments caudal to the injury, in non-allodynic and allodynic halothane anaesthetised rats and from comparable neurones in normal rats. To assess spinal GABAergic inhibition in the three groups of animals, spontaneous and evoked cell firing rates were recorded before, during and after microiontophoretic application of the GABA(A) receptor antagonist bicuculline. Administration of bicuculline to normal animals resulted in significant and reversible increases in the receptive field size, spontaneous firing rate, response to brushing and pinching the skin and afterdischarge activity of dorsal horn neurones, as well as decreasing paired-pulse depression of responses evoked by transcutaneous electrical stimulation. In non-allodynic SCI animals, bicuculline ejection led to significant changes in receptive field size, paired-pulse depression and responses to brush and pinch stimulation that were comparable to those observed in normal animals. By contrast, in allodynic SCI animals, bicuculline ejection had little or no effect on dorsal horn neurone responses to mechanical skin stimuli and paired-pulse depression despite reliably blocking the inhibition of cell firing produced by similarly applied GABA. The demonstration of reduced GABAergic inhibition predominantly in the allodynic SCI rats suggests that such a deficiency contributed to this pain-related behaviour acutely following SCI.

Dendritic Spine Remodeling After Spinal Cord Injury Alters Neuronal Signal Processing

“…The hyperexcitable state of DH neurons after injury is chronic and resilient, which suggests that injury-induced changes to pain-sensory signal processing within the nervous system reside in a firmly established pathological state. Processes that are known to contribute to DH hyperexcitability include: the loss of inhibitory GABAergic input (Drew et al 2004), changes to postsynaptic receptors (Agrawal and Fehlings 1997;South et al 2003), abnormal expression of sodium ion channels (Hains et al 2003;Waxman and Hains 2006), and aberrant remodeling of afferent fibers and their branches (Romero et al 2000;Woolf et al 1992).…”

Neuropathic Pain Memory Is Maintained by Rac1-Regulated Dendritic Spine Remodeling after Spinal Cord Injury

“…Alterations in sodium channel expression in dorsal horn neurons (Hains et al, 2003), the loss of inhibitory GABAergic inputs (Drew et al, 2004), and injury-induced synaptic plasticity (Ji et al, 2003) contribute to neuronal hyperexcitability associated with post-SCI neuropathic pain. Given our results, we asked whether abnormal spine features after SCI can also contribute to single-unit hyperexcitability.…”

Estratégia terapêutica após contusão da medula espinhal: recuperação funcional e estabilidade cortical sensório-motora

“…Harkema ( Nos dias de hoje, muitos trabalhos têm feito uso de auxílio robótico durante o treinamento na esteira com suporte de peso tanto em humanos (Winchester et al, 2005;Duschau-Wicke et al, 2010;Hussain et al, 2011), como em modelos animais (Fong et al, 2005;Cai et al, 2006;Lee et al, 2011 (Drew et al, 2004;Hutchinson et al, 2004;Kloos et al, 2005;Zhang et al, 2005;Gwak et al, 2006;Gwak et al, 2008) A metodologia adotada no nosso trabalho para avaliar a dor neuropática foi usar três monofilamentos que indicam a presença de alodínea, hiperalgesia mecânica leve e hiperalgesia mecânica intensa (Takasaki et al, 2001). Vale ressaltar que para avaliar dor abaixo do nível de lesão é preciso utilizar métodos que levem em consideração o substrato neuronal supostamente envolvido neste tipo de dor.…”

“…(Berger et al, 2011;Woolf, 2011 Sabe-se que a LM traumática causa uma diminuição do tônus GABAérgico e glicinérgico na medula espinhal, em grande parte devido à apoptose de interneurônios inibitórios, resultando frequentemente em dor neuropática (Drew et al, 2004;Gwak et al, 2006;Gwak et al, 2008). Já foi mostrado também que o treinamento na esteira é capaz de modular a inibição mediada por GABA e glicina na medula espinhal adulta de gatos lesados (Maier e Schwab, 2006 Pesquisadores afirmam que a plasticidade de centros neuronais na medula espinhal pode ser potencializada por meio de um treinamento específico tanto em humanos, como em modelos experimentais (Bregman, 1998;Basso, 2000;Dietz, 2002;Houle e Tessler, 2003;Dietz, 2003).…”

“…Em modelos animais lesados medulares com dor neuropática são investigados os mecanismos relacionados a esta condição, fornecendo importantes resultados aplicados à prática clínica (Drew et al, 2004;Kloos et al, 2005;Zhang et al, 2005;Erschbamer et al, 2006;Keer e David, 2007;Gwak et al, 2008 …”