Therapeutic nerve blocks for chronic pain: An unexplored potential
Updated: Apr 12, 2022
An old treatment, still considered as investigational
One of my patients with severe daily headache greatly benefitted from anesthetic injections of the greater occipital nerve. I performed a series of 4 weekly injections under ultrasound guidance. I am proud to be part of the research team that has developed the procedure in year 2010 (see here).
My patient experienced substantial benefits for 3-4 months after end of the series, with lower pain levels and return to work. The series had to be repeated every 4-6 months, as the severe pain came back.
At a certain point, her insurance stopped covering the procedure, stating that they consider greater occipital nerve blocks investigational, in other words, not supported by enough evidence. I have submitted the studies on this treatment, without success. The patient has no alternatives, as all other treatments provided by a highly specialized Headache Clinic have failed.
Short-lasting effect for long-lasting benefit?
Nerve blocks consist in injecting a local anesthetic close to nerves. They can be performed to contribute to the diagnosis of pain conditions (diagnostic or test blocks), to screen patients for nerve ablations (prognostic blocks), or to treat chronic pain (therapeutic blocks).
Therapeutic nerve blocks for chronic pain are conceptually problematic, as the duration of action of local anesthetics is short. In a previous blog I have discussed why anesthetic nerve blocks, while lasting only few hours, may still benefit patients with chronic pain.
The practice of therapeutic nerve blocks to treat chronic pain remains controversial and very heterogenous. The blocks are not mentioned in practice guidelines. Some practitioners never use therapeutic nerve blocks, whereas other ones offer them on a daily basis.
The reason for the unclear role of nerve blocks in the management of chronic pain is the almost complete lack of high quality research. Can we improve it?
Despite decades of practice, research has been sparse and of poor quality
When the specialty of Pain Medicine was founded, nerve blocks were among the few available tools. However, the practice of nerve blocks has not kept pace with the science required to establish their efficacy and effectiveness. Very limited data exist on their efficacy in the middle- or long-term, and on the comparative effectiveness with alternative treatments. There has been virtually no research on the mechanisms of action of therapeutic nerve blocks.
The rules of evidence-based medicine
Rigorous evaluation of the efficacy of a treatment requires adherence to rules in clinical trials. One is randomization, consisting in allocating patients randomly to one treatment or another. Another rule is blinding, whereby patients and research staff are not aware of which treatment has been administered. These measures aim to minimize bias when evaluating whether a treatment is superior, inferior, or equal to another one. Placebo-controlled studies are considered the gold standard to determine whether the effect can be specifically attributed to the treatment and not to other factors, such as the natural course of the pain or placebo (see here to learn more about placebo for nerve blocks). These studies are typically required by regulatory agencies to approve treatments, and by health insurances to determine coverage.
For most therapeutic nerve blocks, placebo-controlled studies are unfeasible or nonsensical
Many patients are not willing to be randomized to nerve blocks or placebo. The effects need to be evaluated in the long term, and patients want to proceed directly to a treatment that may help them, rather than waiting few months to switch from placebo to the "real" procedure. In addition, blinding is frequently unfeasible, as nerve blocks can cause numbness and/or weakness. Therefore, patients and study staff will likely guess what treatment has been administered.
Is superiority to placebo really required?
The question whether a treatment works better than placebo is in general more relevant to the scientific community and regulatory agencies than to health care professionals and patients. Both health care professionals and patients are interested in the question whether the treatment is associated with an improvement or not. When we offer a treatment and observe an improvement, we cannot rule out that the improvement is due to a placebo effect. However, a placebo response to a treatment implies that the improvement would not happen if the treatment had not been performed. As long as the treatment serves its purpose to help patients, the question of placebo response may be of secondary importance from a clinical point of view, provided that the benefit/harm balance is favorable.
If placebo-controlled studies are hardly feasible and placebo is a welcomed effect, why should we pursue placebo-control studies? Do we have alternative ways to evaluate the usefulness of therapeutic nerve blocks and determine their role in the management of chronic pain?
Pragmatic approaches are warranted
Observational cohort studies are inferior to randomized controlled trials in providing evidence for effectiveness. However, prospective studies in large patient populations, with long-term follow-up, and including all relevant outcomes such as physical and psychosocial functioning, are largely lacking for nerve blocks and would be of great value. While these studies would not tell us whether changes in outcomes are specifically due to the nerve blocks rather than other causes, they would provide real-world information in several domains and address questions such as:
How many patients respond?
For which pain syndromes are nerve blocks effective?
Which patients are most likely to benefit?
What is the rate of adverse events?
Studies that compare nerve blocks to other, more established, treatments of chronic pain would also greatly advance the field. For instance, one would wonder how nerve blocks compare with anticonvulsants, such as gabapentin or pregabalin, for the treatment of neuropathic pain. Because anticonvulsants have been shown to be superior to placebo for different forms of neuropathic pain, a non-inferiority would suggest that nerve blocks may have a specific effect on neuropathic pain. If non-inferior, the many patients who do not tolerate anticonvulsants due to side effects or do not want to take medications, may prefer nerve blocks. These studies are called "comparative-effectiveness clinical trials" and have an established role in clinical research. Despite some limitations, they are close to real world and represent an excellent resource to inform clinical practice and establish clinical guidelines.
This is the right time
The opioid crisis has prompted massive investments in pain research, aiming to study non-opioid treatment strategies. The NIH HEAL Initiative is funding hundreds of studies on pain. Nerve blocks have become very accurate and safe, also thanks the development of ultrasound guidance (see figure).
This is a great time for funding agencies to support and for clinical researchers to conduct high quality pragmatic studies on therapeutic nerve blocks. These studies would be great service to patients and to the health care professionals who take care of patients with chronic pain.