Antibodies are proteins in our blood that work as part of our immune system. When a virus or bacteria enters the body, our antibodies attach to its cells to fight it off and protect us. In a healthy body with a well-functioning immune system, antibodies are produced naturally by the white blood cells.

Monoclonal antibodies (mAbs) are antibodies made by scientists in a laboratory. They’re designed to attach to specific molecules to fight them or stop their function. The World Health Organization describes mAbs as: “immunoglobulins derived from a monoclonal cell line and which have a defined specificity.”

mAbs were first developed in 1975. Since then they have been further researched and developed to treat a range of problems.

These man-made antibodies can be made from human proteins, mouse proteins, or a combination of both. I know that sounds a bit scary, but don’t worry they’re thoroughly tested to make sure they’re safe for people. 

Research is ongoing on the treatment of various chronic pain conditions using mAbs. Initial results suggest they could be a highly effective, targeted treatment. This detailed article states that mAbs: “are directed against specific, targeted molecules involved in pain signaling and processing pathways that look to be very effective and promising as a novel therapy in pain management.”

So, how can they help to treat chronic pain? Well, evidence suggests that they can interrupt processes that cause and worsen chronic pain. For example, they can reduce inflammation, tackle central sensitization, and block specific pain signals.

This 2021 article on mAbs for chronic pain states: “Despite the type of pain (nociceptive or neuropathic), the role of inflammation in chronification and sensitization is clearly demonstrated.” Some mAbs can reduce inflammation by blocking proteins which cause an inflammatory reaction within the body. This in turn could reduce pain.

Scientists are working to develop mAbs which target specific proteins that play a part in causing pain and making it chronic. This detailed article states: “Inactivation of pleiotrophic cytokines such as tumor necrosis factor (TNF), epidermal growth factor receptor, and nerve growth factor (NGF) are key targets for mAbs in the treatment of pain.”

The nerve growth factor (NGF) plays a vital part in the nervous system. However, it’s also involved in sending pain signals and can cause elevated pain levels. If scientists can block the action of the NGF without negatively affecting the rest of the nervous system, in theory, they can reduce pain levels.

This 2019 study states that: “Although the role of NGF in chronic pain signaling is not fully understood, it is believed to contribute to chronic pain by promoting neuronal sensitization (ie, increased nervous system excitability) and, possibly, by driving local neuronal sprouting at sites of inflammation.”

mAbs have been studied as a treatment for migraine, daily persistent headaches, cancer-related pain, arthritis and back pain with positive results. Studies on the use of mAbs for migraine found they: “led to significant reductions from baseline in either episodic and/or chronic monthly migraine or headache days vs. placebo.”

Another 2023 study on the use of mAbs to treat migraine compared with traditional medications discovered that in the three months after starting the treatment: “both groups presented headache frequency reduction, but those with monoclonal antibodies had a significantly higher reduction in the number of headache days and symptomatic medication intake when compared to the control (p < 0.0001).” So mAbs were more effective than regular prescription medications in treating migraines.

There is also ongoing research focusing on mAbs which target gated sodium channels on the surface of cells to control pain. You can think of the antibodies they are trying to develop like a ‘key’ that they are developing to fit into a ‘gate’, which will block the cell from sending pain signals.

The project is led by Professor Vladimir Yarov-Yarovoy and James Trimmer from the UC Davis School of Medicine. In this 2022 article from the University of California, Yarov-Yarovoy explains: “Voltage-gated sodium ion channels in nerve cells are the key transmitters of pain. We aim to create antibodies that will bind to these specific transmission sites at the molecular level, inhibiting their activity and stopping the transmission of pain signals.”

Research has also shown some promise for mAbs in the treatment of lower back pain, although the treatment hasn’t been more successful than other traditional treatments. Studies are ongoing on the use of mAbs for fibromyalgia and endometriosis.

There are several types of mAbs, which simply means they are designed to target different proteins in the body and have different effects. We’ll go through some of the most common types.

Anti-Nerve Growth Factor (NGF)

As we discussed earlier, the NGF is involved in sending pain signals. Anti-NGF mAbs work to bind to the NGF and block its interaction with other parts of the nervous system, preventing pain signals from being sent.

Types of anti-NGFs include:

• Tanezumab
• Fulranumab
• Fasinumab

TNF Inhibitors

TNF inhibitors target a protein called tumour necrosis factor (TNF) which causes inflammation. Different types of TNF can treat diseases including types of arthritis, crohn’s disease, ulcerative colitis, and plaque psoriasis.

Types of TNF inhibitors include:

• Certolizumab pegol
• Infliximab
• Adalimumab
• Etanercept
• Golimumab
• Eptinezumab
• Erenumab

Calcitonin Gene-Related Peptide (CGRP) Inhibitors

CGRP is a protein that is involved in the function of the nerves that connect to the head and neck. It’s thought to be part of the cause of the pain felt during migraines. CGRP inhibitors work to block the effect of this protein, therefore reducing pain.

Types of CGRP inhibitors include:

• Fremanezumab
• Galcanezumab
• Sarilumab

Interleukin Blockers

Interleukins are part of the immune system. There are lots of different types of interleukins. However, when the body overproduces certain types it can cause inflammation and other problems. Interleukin blockers work to stop these issues by blocking the effect of specific interleukins.

In particular, a protein called IL-6 plays a role in causing inflammation in the body. IL-6 receptor inhibitors prevent IL-6 from binding to receptors in the body, which stops it from causing inflammation.

Types of interleukin blockers include:

• Tocilizumab
• Sarilumab
• Adalimumab
• Golimumab

B-cell Inhibitors

B-cells play an important role in the immune system in making antibodies. When they’re overactive, they can cause issues like an autoimmune response and excessive inflammation. B-cell inhibitors stop the function of B cells. The main B-cell inhibitor you’ll hear of is Rituxan (rituximab).

Of course, the most obvious benefit of mAbs is the reduction of pain. Lower pain levels can improve quality of life and increase the patient’s ability to function.

However, there are also additional benefits. Unlike many medications which need to be taken daily or weekly, mAbs have a long half-life. That means they stay in your system and stay effective for longer. Therefore, they don’t have to be given as often, making them easier to tolerate and meaning patients are more likely to keep up with treatments.

Compared to many medications such as opioids, they are far less likely to cause serious side effects on the nervous system. This 2021 article explains that: “due to their molecular characteristics, they have a high limited ability to cross the blood–brain barrier, reducing the possibility of CNS (central nervous system) adverse events.”

Since the treatment is so targeted and specific, it’s less likely to cause systemic side effects than many other treatments. This 2023 book on the topic states: “mAbs can be applied to target precise targets whilst limiting the effects on alternate systems.”

mAbs are typically used to fight cancer, inflammation, or viruses. They’re often used to treat people with autoimmune conditions, such as multiple sclerosis (MS) or rheumatoid arthritis (RA).

Over the coming years, these treatments may become more widely available for chronic pain. At the moment, the Food and Drug Administration (FDA) has approved the treatment for migraine, but not yet other chronic pain conditions.

In the future, they may be offered where other chronic pain treatments have failed. However, it’s important to note that using mAbs to treat chronic pain is still being studied and developed. It may be some time before they are available to pain patients.

The treatment is usually given by injection or IV infusion. This is typically done in a doctor’s office, outpatient clinic, or hospital setting. However, in some cases, patients may be able to give themselves the injections at home. This depends mostly on the type of medication patients are given, as well as other factors. The first treatment is always done in a medical setting to monitor patients for an allergic reaction.

If patients are given an infusion, this means they will have a tiny tube that goes into their vein which is attached to a ‘bag’ of the medication. A pump controls the rate at which the medication moves from the back, through the tube and into the vein. You might also know this as being on a ‘drip’.

Infusions of mAbs usually take between two and four hours. The treatment is typically given once every month or a few months depending on the type of mAb and your needs. 

Like all medications, mAbs can cause some side effects. There are some serious risks to taking this medication.

One of the main risks is that the antibodies affect how your immune system functions so you may be more vulnerable to infection. Before starting the treatment, your doctor will give you blood tests to check for current infections. You will also need to take precautions to avoid infection during treatment.

Additionally, you may not be able to have vaccines while on this treatment. Your doctor should check you are up to date with your vaccinations before starting treatment.

Other potential side effects and risks include:

• A reaction at the site of the needle: This may include irritation, itching, swelling, pain, redness, or a rash.
• Flu-like symptoms: For example, nausea, diarrhoea, fever, fatigue, etc.
• Cytokine release syndrome: This can also be known as a cytokine storm or cytokine-associated toxicity. It essentially means that your immune system has an overreaction and your body releases chemicals called cytokines. Symptoms of cytokine release syndrome can include fever, nausea, a drop in blood pressure, breathing issues, fast heart rate, muscle pain, confusion, and a rash. It can range from mild to severe (in some cases it can be life-threatening). 
• Capillary leak syndrome: This involves fluid leaking out of blood vessels into the tissues around them. It can lead to low blood pressure, organ failure, and can even be fatal if left untreated. 
• Allergic reactions: These can range from mild to severe (anaphylaxis).
• Heart issues: These include an increased risk of heart attack and heart failure. 
• Skin irritation: Skin reactions may include sores on the skin and mouth, rashes, and dry skin which range from mild to moderate. 
• Inflammatory lung disease: Symptoms may include a cough and shortness of breath. 
• Increased risk of cancer: This only occurs with specific mAbs.
• High blood pressure: Some mAbs can increase the risk of high blood pressure, but this risk varies greatly.

Many studies so far suggest that the treatment is generally well tolerated. This 2021 systematic review and meta-analysis of the effect of anti-nerve growth factor mAbs to treat osteoarthritis found that: “The most commonly reported adverse events associated with anti-NGF antibody use include peripheral oedema, joint and extremity pain, and peripheral neuropathy.”

Of course, one of the other risks is that the treatment may not work for you. Although many people may find it’s successful and can help reduce their chronic pain, others may find it doesn’t help at all. 

Monoclonal antibodies show great promise as a viable treatment for chronic pain. Research suggests that they are effective, well tolerated, and potentially a safer alternative than opioids. However, more research is needed before they are made widely available to patients.