Knock down of the α5 nicotinic acetylcholine receptor in spinal nerve-ligated rats alleviates mechanical allodynia
Review articleOpen access

AbstractNicotinic acetylcholine receptor (nAChR) agonists are known to alleviate neuropathic and inflammatory pain via activation of a heterogeneous population of receptors. However, the function of nAChRs in the maintenance of neuropathic pain is not known. Spinal nerve ligation (SNL) increases the spinal expression of the α5 nAChR subunit ipsilateral to injury. The α5 subunit is unique because it modifies numerous characteristics of existing functional nAChRs, but it does not form functional nAChRs when expressed alone or with β nicotinic subunits. Because there are no α5 subunit selective ligands, we used antisense oligonucleotides (ODNs) to assess the contribution of the α5 subunit to the maintenance of mechanical allodynia following SNL. Intrathecal antisense oligonucleotides were administered to SNL rats after the development of mechanical allodynia (10–12 days post-SNL). I.t. antisense specifically reduced α5 immunoreactivity (α5-IR) by 50–70% in the outer laminae of the dorsal horn and moderately alleviated mechanical allodynia. Furthermore, using the phosphorylation of cAMP response element-binding protein (pCREB) as a general marker of neuronal activation, a significant increase in pCREB immunoreactivity was observed in SNL rats. Treatment of SNL rats with α5-antisense significantly reduced pCREB immunoreactivity. These results suggest that the increased expression of the α5 nAChR subunit following SNL contributes to spinal CREB phosphorylation and the maintenance of mechanical allodynia.

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