Steroid injections for chronic pain: How do they work (and why they may not)

Cortisol (from Wikipedia)

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Corticosteroids, often referred to as steroids, are synthetic versions of hormones naturally produced by the adrenal glands. They are commonly administered via injection to help manage chronic pain. But how do they work, and why do they often seem ineffective?

How do steroid injections work?

Corticosteroids can reduce pain through multiple mechanisms:

• Gene regulation: Once inside the cell, corticosteroids reduce the expression of genes that promote inflammation, and increase the expression of anti-inflammatory genes.

• Suppression of inflammatory mediators: Corticosteroids inhibit various proteins and enzymes responsible for producing inflammatory substances and causing pain, including prostaglandins, interleukins, and tumor necrosis factor-alpha.

• Control of vascular response: By stabilizing blood vessels, corticosteroids limit fluid leakage into tissues, reducing swelling and the pressure that may contribute to pain.

• Immune Modulation: Corticosteroids decrease the activity of white blood cells that contribute to inflammation.

Are steroid injections helpful in chronic pain?

Steroids can be injected into various parts and organs of the body, including nerves, joints, muscles, and the epidural space. Despite the expectations, rigorous research has shown that the effectiveness of steroid injections for chronic pain is often less impressive than anticipated. Many studies indicate that these injections either do not work beyond a placebo effect or offer, on average, only modest and temporary relief. Few patients experience substantial benefit.

Why aren't steroids more effective?

Chronic pain conditions are not necessarily inflammatory. For instance, the joints of the spine are a possible source of back pain. However, it is unclear whether joint inflammation is present at all in back pain; if not, steroids will not be efficacious. 

Even when inflammation or immune cell involvement is confirmed in a chronic pain condition, they might not be the primary cause of the pain. For example, despite rheumatoid arthritis being an inflammatory condition, research shows a weak and unclear link between inflammation levels and pain severity. A study has provided insights into this discrepancy, revealing the growth of nerve fibers that transmit pain sensations into the joints of patients with rheumatoid arthritis. The activity of these nerve fibers might be more directly related to the sensation of pain than the level of joint inflammation. Since steroids do not affect these nerve fibers, they may reduce inflammation but have little effect on the pain itself. Similar mechanisms might be present in other pain conditions.

An overlooked side effect of steroid injections

Steroids must be used responsibly because they can have side effects. While an exhaustive list of side effects is beyond the scope of this discussion, one often overlooked side effect pertains to the potential intereference of steroid injections with the natural production of cortisol, a crucial hormone produced by the adrenal glands. Here’s how:

1. The hypothalamic-pituitary-adrenal axis regulates cortisol levels: the hypothalamus (a region of the brain) sends signals to the adrenal gland to increase or decrease cortisol production based on the needs of the body.

2. When steroids are administered, they mimic cortisol’s effects.

3. This signals the brain to reduce stimulation of the adrenal glands.

4. The adrenal glands may become less active, leading to reduced cortisol production.

In fact, a study on epidural steroids found that 20.3% of patients experienced reduced cortisol levels greater than 50% three weeks after the injection, compared to only 6.7% in patients who received epidural lidocaine alone. This indicates that steroids do not act solely locally; they are absorbed into the bloodstream and can affect the entire body, including brain regions responsible for cortisol production.

Symptoms of reduced cortisol production can range from mild to severe:

Possible side effects of reduced cortisol production following a steroid injection.

Side effects related to cortisol suppression are frequently undiagnosed; patients and health professionals may not associate them with the steroid injection.

Are steroid injections then meaningful?

Steroids should not be used without a clear rationale. For example, trigger point injections are performed to relieve so-called myofascial pain, a common condition characterized by tenderness of muscles. However, there is no evidence that pain from those points is associated with inflammation or immune mechanisms in the tender muscles.

In the case of nerve blocks, the use of steroids relies on the assumption that inflammatory or immune processes in the nerve are causing the pain. However, in most instances, it is difficult to determine or rule out nerve inflammation, as we lack diagnostic tools for this purpose.

Here is a proposed guidance:

• Adding a steroid to a local anesthetic as a routine for any injection for chronic pain is not appropriate.

• If an inflammatory process is demonstrated or suspected, a steroid injection may be meaningful.

• However, in this case the injection should be performed at the site of ascertained or suspected inflammation. Nerve blocks are frequently performed proximal to the site of pathology, in which case the steroid would not do anything for the pain.

• There is no meaningful rationale for adding a steroid to a local anesthetic when performing diagnostic or prognostic nerve blocks.

• An example of a potentially beneficial application is the use of a greater occipital nerve block to treat occipital neuralgia. This condition may involve nerve irritation that triggers immune and/or inflammatory responses, which the steroid can help reduce. However, it is important to note that we lack diagnostic tools to confirm nerve inflammation, and there is no solid evidence that using a steroid is more effective than using just a local anesthetic for occipital neuralgia.