Botulinum toxin for chronic pain: What's on the horizon?

Botulinum toxin (BoNT) was first approved by the US Food and Drug Administration (FDA) for the treatment of strabismus and blepharospasm in 1989. Since then, approved indications have expanded to include spasticity, cervical dystonia, severe axillary hyperhidrosis, bladder dysfunction, and chronic migraine headache, as well as multiple cosmetic uses.^1,2 Over the course of 30 years of clinical use, BoNT has proven to be effective and safe.^3,4 This has led to the expanded use of BoNT for additional medical conditions.^1,2

In the review that follows, we will discuss the utility of BoNT in the treatment of headaches, spasticity, and cervical dystonia. We will then explore the evidence for emerging indications that include chronic joint pain, trigeminal neuralgia, and plantar fasciitis. But first, a brief word about how BoNT works and its safety profile.

Seven toxins, but only 2 are used for medical purposes

BoNT is naturally produced by Clostridium botulinum, an anaerobic, spore-forming bacteria.¹ BoNT inhibits acetylcholine release from presynaptic vesicles at the neuromuscular junctions, which results in flaccid paralysis in peripheral skeletal musculature and autonomic nerve terminals.^1,5 These effects from BoNT can last up to 3 to 6 months.¹

Seven different toxins have been identified (A, B, C, D, E, F, and G), but only toxins A and B are currently used for medical purposes.⁵ Both have similar effects, although there are slight differences in mechanism of action. Toxin B injections are also reported to be slightly more painful. There are also differences in preparation, with some requiring reconstitution, which vary by brand. Certain types of BoNT require refrigeration, and an in-depth review of the manufacturer’s guidelines is recommended before use.

Safety and adverse effects

Although BoNT is 1 of the most lethal toxins known to humans, it has been used in clinical medicine for more than 30 years and has proven to be safe if used properly.³ Adverse effects are rare and are often location and dose dependent (200 U and higher). Immediate or acute adverse effects are usually mild and can include bruising, headache, allergic reactions, edema, skin conditions, infection, or pain at the injection site.⁴ Delayed adverse effects can include muscle weakness that persists throughout the 3 to 6 months of duration and is usually related to incorrect placement or unintentional spread.⁴

Serious adverse events are rare: there are reports of the development of botulism, generalized paralysis, dysphagia, respiratory effects, and even death in patients who had received BoNT injections.³ In a majority of cases, a direct relationship with BoNT was never established, and in most incidents reported, there were significant comorbidities that could have contributed to the adverse event.³ These events appear to be related to higher doses of BoNT, as well as possible incorrect injection placement.³

Knowledge of anatomy and correct placement of BoNT are vitally important, as they have a significant impact on the effectiveness of treatment and adverse events.³ In preventing adverse events, those administering BoNT need to be familiar with the BoNT brand being used, verify proper storage consistent with the manufacturer’s recommendations, and confirm correct dosages with proper reconstitution process.³

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