Neuropathic pain (NP) embraces a broad range of conditions linked with a disease or lesion of the peripheral or central somatosensory system and its prevalence in the general population may be as high as 7-10%. Up to the present, the larger part of our understanding of pain mechanisms come from basic sciences studies which has resulted in a vast increase in our knowledge. The obvious issues in translational pain research reveal the limitations of certain experimental models, and on that account result of limitations in clinical research. In spite of such difficulties, the scientific community wish for a better understanding of pain mechanisms helped by the new insights of basic research. For that reason, the first of the three parts of this work aim to recognise additional changes in the somatosensory system through a series of experiments done in an experimental model of NP.
NP following peripheral nerve injury is associated with hyperexcitability in damaged myelinated sensory axons, which begins to normalise over time. We investigated the composition and distribution of shaker-type-potassium channels (Kv1 channels) within the nodal complex of myelinated axons following injury. At the neuroma that forms after damage, expression of Kv1.1 and 1.2 was markedly decreased. In contrast Kv1.4 and 1.6, which were hardly detectable in the naıve state, showed increased expression following injury. Within the dorsal root we noted a redistribution of Kv1-channels towards the paranode. Blockade of Kv1 channels with a-DTX after injury reinstated hyperexcitability of A-fibre axons and enhanced mechanosensitivity. Changes in the molecular composition and distribution of axonal Kv1 channels, therefore represents a protective mechanism to suppress the hyperexcitability of myelinated sensory axons that follows nerve injury.
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