HCN2 ion channels – drivers of chronic pain and tinnitus

The HCN4 ion channel is well known for driving pacemaker activity in the heart and thus modulating the heart rate. The McNaughton lab has discovered that HCN2, a different member of the same family, plays a similar role in nerve fibres. When HCN2 is activated by inflammatory mediators released following tissue damage, then the firing of nerve action potentials is potentiated in nerve fibres which transmit the sensation of pain. Blocking the HCN2 ion channel may therefore provide analgesia, but blockers must be highly selective to avoid blocking the HCN4 ion channel which drives the heartbeat. We have found that HCN2-selective blockers can deliver remarkable analgesia in animal pain models, and thus may offer effective analgesia in poorly treated pain conditions such as neuropathic pain, an intractable pain condition caused by nerve damage. In more recent work we have found that HCN2 ion channels expressed in the auditory nerves may also be the drivers of tinnitus, another common and distressing condition associated with nerve damage.