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Tactile allodynia can occur in the spared nerve injury model in the rat without selective loss of GABA or GABA(A) receptors from synapses in laminae I-II of the ipsilateral spinal dorsal horn.

Polgár E, Todd AJ - Neuroscience (2008)

Bottom Line: We found no difference in the intensity of immunolabeling for any of these markers on the two sides of the superficial dorsal horn.These results suggest that there is no significant loss of GABAergic boutons from the denervated area after SNI (which is consistent with the finding that neuronal death does not occur in this model) and that there is no depletion of GABA or GABA(A) receptors at GABAergic synapses within this region.An alternative explanation for disinhibition after nerve injury is that it results from reduced excitatory drive to GABAergic dorsal horn neurons following loss of primary afferent input to these cells.

View Article: PubMed Central - PubMed

Affiliation: Spinal Cord Group, Faculty of Biomedical and Life Sciences, West Medical Building, University of Glasgow, University Avenue, Glasgow G12 8QQ, UK. e.polgar@bio.gla.ac.uk

ABSTRACT
Although there is evidence that reduced inhibition in the spinal dorsal horn contributes to neuropathic pain, the mechanisms that underlie this are poorly understood. We have previously demonstrated that there is no loss of neurons from laminae I-III in the spared nerve injury (SNI) model [Polgár E, Hughes DI, Arham AZ, Todd AJ (2005) Loss of neurons from laminas I-III of the spinal dorsal horn is not required for development of tactile allodynia in the SNI model of neuropathic pain. J Neurosci 25:6658-6666]. In this study we investigated whether there was a difference between ipsilateral and contralateral sides in the levels of GABA, the vesicular GABA transporter (VGAT), or the beta3 subunit of the GABA(A) receptor at synapses in the medial part of the superficial dorsal horn in this model. Tissue from rats that had undergone SNI 4 weeks previously was examined with an electron microscopic immunogold method to reveal GABA, following pre-embedding detection of GABA(A) beta3 to allow identification of GABAergic terminals. Assessment of labeling for the GABA(A) beta3 subunit and VGAT was performed by using immunofluorescence and confocal microscopy. We found no difference in the intensity of immunolabeling for any of these markers on the two sides of the superficial dorsal horn. These results suggest that there is no significant loss of GABAergic boutons from the denervated area after SNI (which is consistent with the finding that neuronal death does not occur in this model) and that there is no depletion of GABA or GABA(A) receptors at GABAergic synapses within this region. An alternative explanation for disinhibition after nerve injury is that it results from reduced excitatory drive to GABAergic dorsal horn neurons following loss of primary afferent input to these cells.

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Graph showing 50% withdrawal thresholds to von Frey hairs in the SNI rats (n=11). Results for ipsilateral (ipsi) and contralateral (contra) hind paws are shown and each point represents the mean±S.D. *** Significant difference (P<0.001) between the ipsilateral and contralateral paws (one-tailed unpaired t-test).
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fig1: Graph showing 50% withdrawal thresholds to von Frey hairs in the SNI rats (n=11). Results for ipsilateral (ipsi) and contralateral (contra) hind paws are shown and each point represents the mean±S.D. *** Significant difference (P<0.001) between the ipsilateral and contralateral paws (one-tailed unpaired t-test).

Mentions: All of the rats that had undergone SNI showed alterations in their posture. They often held up the affected paw with the toes plantar-flexed, and tended to avoid bearing weight on it. Within the first post-operative week there was already a substantial reduction in the 50% paw withdrawal threshold to tactile stimulation on the side ipsilateral to the nerve injury, and from the end of the first week, mean values were consistently below 1 g, compared with pre-operative values of >20 g (Fig. 1). Threshold values for the ipsilateral hind paw were significantly lower than those for the contralateral paw from post-operative day 1 to day 28 (P<0.001, one-tailed unpaired t-test).


Tactile allodynia can occur in the spared nerve injury model in the rat without selective loss of GABA or GABA(A) receptors from synapses in laminae I-II of the ipsilateral spinal dorsal horn.

Polgár E, Todd AJ - Neuroscience (2008)

Graph showing 50% withdrawal thresholds to von Frey hairs in the SNI rats (n=11). Results for ipsilateral (ipsi) and contralateral (contra) hind paws are shown and each point represents the mean±S.D. *** Significant difference (P<0.001) between the ipsilateral and contralateral paws (one-tailed unpaired t-test).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2553186&req=5

fig1: Graph showing 50% withdrawal thresholds to von Frey hairs in the SNI rats (n=11). Results for ipsilateral (ipsi) and contralateral (contra) hind paws are shown and each point represents the mean±S.D. *** Significant difference (P<0.001) between the ipsilateral and contralateral paws (one-tailed unpaired t-test).
Mentions: All of the rats that had undergone SNI showed alterations in their posture. They often held up the affected paw with the toes plantar-flexed, and tended to avoid bearing weight on it. Within the first post-operative week there was already a substantial reduction in the 50% paw withdrawal threshold to tactile stimulation on the side ipsilateral to the nerve injury, and from the end of the first week, mean values were consistently below 1 g, compared with pre-operative values of >20 g (Fig. 1). Threshold values for the ipsilateral hind paw were significantly lower than those for the contralateral paw from post-operative day 1 to day 28 (P<0.001, one-tailed unpaired t-test).

Bottom Line: We found no difference in the intensity of immunolabeling for any of these markers on the two sides of the superficial dorsal horn.These results suggest that there is no significant loss of GABAergic boutons from the denervated area after SNI (which is consistent with the finding that neuronal death does not occur in this model) and that there is no depletion of GABA or GABA(A) receptors at GABAergic synapses within this region.An alternative explanation for disinhibition after nerve injury is that it results from reduced excitatory drive to GABAergic dorsal horn neurons following loss of primary afferent input to these cells.

View Article: PubMed Central - PubMed

Affiliation: Spinal Cord Group, Faculty of Biomedical and Life Sciences, West Medical Building, University of Glasgow, University Avenue, Glasgow G12 8QQ, UK. e.polgar@bio.gla.ac.uk

ABSTRACT
Although there is evidence that reduced inhibition in the spinal dorsal horn contributes to neuropathic pain, the mechanisms that underlie this are poorly understood. We have previously demonstrated that there is no loss of neurons from laminae I-III in the spared nerve injury (SNI) model [Polgár E, Hughes DI, Arham AZ, Todd AJ (2005) Loss of neurons from laminas I-III of the spinal dorsal horn is not required for development of tactile allodynia in the SNI model of neuropathic pain. J Neurosci 25:6658-6666]. In this study we investigated whether there was a difference between ipsilateral and contralateral sides in the levels of GABA, the vesicular GABA transporter (VGAT), or the beta3 subunit of the GABA(A) receptor at synapses in the medial part of the superficial dorsal horn in this model. Tissue from rats that had undergone SNI 4 weeks previously was examined with an electron microscopic immunogold method to reveal GABA, following pre-embedding detection of GABA(A) beta3 to allow identification of GABAergic terminals. Assessment of labeling for the GABA(A) beta3 subunit and VGAT was performed by using immunofluorescence and confocal microscopy. We found no difference in the intensity of immunolabeling for any of these markers on the two sides of the superficial dorsal horn. These results suggest that there is no significant loss of GABAergic boutons from the denervated area after SNI (which is consistent with the finding that neuronal death does not occur in this model) and that there is no depletion of GABA or GABA(A) receptors at GABAergic synapses within this region. An alternative explanation for disinhibition after nerve injury is that it results from reduced excitatory drive to GABAergic dorsal horn neurons following loss of primary afferent input to these cells.

Show MeSH
Related in: MedlinePlus