Intravenous lidocaine has been used for decades to treat refractory neuropathic pain, however there have only been a modest number of studies with low participant numbers, inconsistent doses and variation in protocols to treat neuropathic pain post trauma or surgery.
The significance of this pilot randomised comparison of dose and placebo is that it will immediately provide best-available evidence to inform which clinical dose achieves the best combination of reduced pain intensity at one week post infusion, weighed against the risk of adverse events for this cohort. The duration of analgesia (recorded up to 12 weeks post infusion) and the effect size for each dose will inform power calculations for larger subsequent clinical trials. Exploratory survival analysis with data from quantitative sensory testing and questionnaires will give new insight into mechanisms of effect and patient profiles that respond best to intravenous lidocaine. The battery of outcomes recorded will provide the foundation for judicious selection of a smaller number of key variables for subsequent clinical trials and evidence to support a priori hypotheses to test the associations between patient profile and response to lidocaine infusion.
Dr Gunjeet Minhas, Tess Cramond Pain and Research Centre, Queensland.
The project was awarded $A19,902 through the ANZCA research grants program for 2022.
This study tested pain relief after intravenous infusion with lidocaine for people who have chronic pain after injury to a nerve in their arms or legs. Injury to nerves can occur with trauma or with surgery, and can result in severe, chronic pain that is difficult to relieve. Lidocaine is a local anaesthetic drug that can be given by intravenous drip in a hospital setting. The response to intravenous lidocaine varies greatly from almost complete pain relief for months, through to no relief or even feeling worse pain after the infusion. Pain is a unique experience for the individual person, with a mix of body and mind factors. Prior to this study there was a lack of information to inform which people will get the best pain relief from the intravenous lidocaine.
To learn more about which people with nerve injuries are more likely to get pain relief from intravenous lidocaine infusion, we did a series of measures for mind and body.
- Measures for the mind were questionnaires about how much the pain interfered/disrupted in their lifestyle, depression, anxiety, stress, and how well they felt that they could cope despite the pain.
- Measures for the body and nervous system included the temperatures at which they felt cold or heat stimuli becoming painful, the pressure at which a 1cm probe feels painful, and the level of pain with a blunt pin-prick.
We measured these a week before and a week after patients attended the hospital for an intravenous infusion. Patients also kept a daily diary of their pain levels, so that we could measure whether the infusion helped with their pain.
The patient, doctors and nurses who provided the infusion were blind to whether it was a 5mg, 3mg or saline placebo dose that they received. That way we would know whether their response was caused by the drug or their expectations of benefit.
Although we had planned to recruit 40 people, in the six months that were available for the study, only six people were able to be recruited, attend the research tests, the infusion and follow-up tests a week later. So this pilot study shows that a larger study in the future would need around 30 months to recruit and test 40 or more people.
- Being the first to test this set of mind and body measures in people with intravenous lidocaine infusion after a nerve injury, we learned a great deal about which people to recruit and how best to do the testing and infusion.
- One person responded really well to the lidocaine infusion, experiencing around 3 months of their pain being halved. Despite the severity of their constant pain, they were unique in being one of the least mentally distressed people, and being much more sensitive to cold near their nerve injury than on the opposite side of their body. One person had more pain after the infusion, even though they received the saline placebo. They were unique in feeling very distressed by their pain, and being more sensitive to pressure near their nerve injury than the opposite side of their body. These results give new clues about who might respond best.
- Our study was one of the first to examine a combination of mind and body measures in people with nerve injury. Although sensory test measures of heat pain, cold pain and pressure pain aim to test how the nerves amplify or diminish what we feel, studies show that these sensory test results are about 20% linked to questionnaire results. For these people with nerve injuries, the heat and pressure pain tests were about 70-90 % linked to the sensory tests. More research is needed to confirm this finding with more participants, but a take-home message from this mind-body relationship is that when treating these people’s pain, we need to look beyond just treating the nerve that was injured, to supporting the whole person, given that they’ve been through traumatic injuries and surgeries.
Australian Pain Society, 44th Annual Scientific Meeting, 2024
- Oral presentation: Can peripheral neuropathic pain be centrally driven? Insights from correlation of peripheral quantitative sensory tests versus psychological questionnaires. Authors: Andrew Claus, Emma Ballard, Gunjeet Minhas, Melissa Cohen, Andre Van Zundert, Scott Farrell, Angela Tognolini, Maree Smith and Paul Gray.
- Poster presentation: Lidocaine Infusion Dose Optimisation for Pain After Injury to Nerves (LIDOPAIN): Pilot feasibility and patient profiles from a double-blind randomised placebo-controlled trial. Authors: Andrew Claus, Emma Ballard, Gunjeet Minhas, Melissa Cohen, Andre Van Zundert, Scott Farrell, Angela Tognolini, Maree Smith and Paul Gray.
Manuscript in preparation for submission to a peer reviewed journal.