Abstract
Large-conductance Ca(2+)-activated K(+) (BK(Ca), MaxiK) channels are important for the regulation of neuronal excitability. Peripheral nerve injury causes plasticity of primary afferent neurons and spinal dorsal horn neurons, leading to central sensitization and neuropathic pain. However, little is known about changes in the BK(Ca) channels in the dorsal root ganglion (DRG) and spinal dorsal horn and their role in the control of nociception in neuropathic pain. Here we show that L5 and L6 spinal nerve ligation in rats resulted in a substantial reduction in both the mRNA and protein levels of BK(Ca) channels in the DRG but not in the spinal cord. Nerve injury primarily reduced the BK(Ca) channel immunoreactivity in small- and medium-sized DRG neurons. Furthermore, although the BK(Ca) channel immunoreactivity was decreased in the lateral dorsal horn, there was an increase in the BK(Ca) channel immunoreactivity present on dorsal horn neurons near the dorsal root entry zone. Blocking the BK(Ca) channel with iberiotoxin at the spinal level significantly reduced the mechanical nociceptive withdrawal threshold in control and nerve-injured rats. Intrathecal injection of the BK(Ca) channel opener [1,3-dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimidazol-2-one] dose dependently reversed allodynia and hyperalgesia in nerve-ligated rats but it had no significant effect on nociception in control rats. Our study provides novel information that nerve injury suppresses BK(Ca) channel expression in the DRG and induces a redistribution of BK(Ca) channels in the spinal dorsal horn. BK(Ca) channels are increasingly involved in the control of sensory input in neuropathic pain and may represent a new target for neuropathic pain treatment.