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  • Title: Depression of C fibre-evoked spinal field potentials by the spinal delta opioid receptor is enhanced in the spinal nerve ligation model of neuropathic pain: involvement of the mu-subtype.
    Author: Buesa I, Urrutia A, Aira Z, Salgueiro M, Bilbao J, Mozas M, Aguilera L, Zimmermann M, Azkue JJ.
    Journal: Neuropharmacology; 2008 Dec; 55(8):1376-82. PubMed ID: 18775732.
    Abstract:
    The depression rate of C fibre-evoked spinal field potentials by spinally applied morphine is increased in two states of spinal hyperexcitation, namely the spinal ligation model (SNL) of neuropathic pain and long-term potentiation (LTP) of C fibre-evoked spinal field potentials. This present work sought to determine opioid receptor subtypes involved in such increase in the SNL model. We recorded spinal field potentials during spinal superfusion with increasing, cumulative concentrations of selective subtype-specific agonists in rats subjected to SNL, as well as in non-ligated animals. The mu opioid receptor (MOR) agonist DAMGO significantly depressed field potentials evoked by C (100 nM) or Adelta fibres (1 microM) both in neuropathic and non-ligated rats, whereas the kappa receptor opioid (KOR) agonist +/-U-50488 was ineffective. The delta opioid receptor (DOR) (D-Ala2)-Deltorphin II was more effective in reducing C fibre-evoked spinal field potentials in rats subjected to SNL (100 nM) than in non-ligated rats (100 microM). Subclinical MOR activation (10 nM DAMGO) produced a leftward shift in (D-Ala2)-Deltorphin II dose-response curve in non-ligated rats (IC50 16.59 +/- 0.99 microM vs 120.3 +/- 1.0 microM in the absence of DAMGO), and isobolar analysis revealed synergistic interaction (interaction index 0.25). MOR blockade (100 microM CTOP) disinhibited C fibre-evoked potentials in neuropathic, but not in basal animals, and partially impeded DOR depression in both groups. DOR blockade (1 mM naltrindole) was ineffective in either group. We show that DOR-mediated depression of spinal responses to peripheral unmyelinated fibre-input is increased in the SNL model, an increase that is contributed to by positive interaction with the spinal MOR.
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