A randomised, blind, placebo controlled crossover study of the influence of the HCN channel-blocker ivabradine on the symptoms of neuropathic pain

Research summary

Chronic pain can arise from direct damage to the nervous system, which is known as nerve or neuropathic pain. Examples include sciatica and the pains caused by shingles or diabetes. Neuropathic pain is pernicious and treatments are often ineffective or limited by side effects. Laboratory-based investigations suggest that mice have been bred so that their pain transmitting nerves lack a certain gene that encodes a protein called HCN2 and do not develop neuropathic pain at all. The HCN channel controls the initiation of electrical impulses within cells and is best known for its role in controlling the heartbeat. The HCN2 channel can be blocked by a drug called ivabradine.

Large studies have shown that ivabradine is a useful treatment for angina and prevents heart attacks. It is licenced for this use in the UK. It is known to be safe and effective but nobody has ever examined whether it might also reduce neuropathic pain. We wish to study whether ivabradine might influence the transmission and thus symptoms of neuropathic pain. We will recruit willing healthy volunteers to take part in this randomised, blind, placebo-controlled, cross-over study. We will temporarily induce neuropathic pain in an area of the forearm using capsaicin (the chemical that makes chilli peppers hot), and measure whether the symptoms are reduced if ivabradine has been taken beforehand. The symptoms can be measured with specialist nerve conduction tests. To avoid bias the volunteers will be blindfolded when they take the tablets with water, thereby making them unidentifiable. During the study, the volunteers will only need to take one tablet on each of their visits and all measurements will be completed within 3 days.


Main inclusion criteria

To be included in the trial the patient must be:

  1. Aged 18 years or over
  2. Able and willing to give written informed consent
  3. Absence of any chronic pain medication
  4. Volunteer in general good health

Main exclusion criteria

The presence of any of the following will preclude patient inclusion:

  1. Pregnancy Pre-existing pain on either forearm
  2. Previous surgery on either forearm
  3. Volunteers with one arm
  4. History of disease associated with neuropathy
  5. Pre-existing chronic pain diagnosis or use of chronic pain medication
  6. Hypersensitivity to capsaicin or ivabradine
  7. Resting heart rate of less than 60 beats per minute
  8. Systolic blood pressure of less than 90mmHg
  9. Any recreational drug use and/or excessive alcohol consumption
  10. Lactose intolerance (placebo may contain lactose)
  11. Diagnosis of sick sinus syndrome
  12. First degree atrioventricular block, or more than two ventricular extrastoles per minute
  13. Use of CYP3A4 inhibitors such as ketoconazole, macrolide antibiotics, nefazodone, nelfinavir and ritonavir

Chief investigator

Dr Daniel Wheeler

Contact details

Clinical Trials ManagerDr Paula Kareclas

Telephone: 01223 596473 | Email: [email protected]