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17 Articles in Volume 20, Issue #1
20/20 with Lynn Webster, MD
Correspondence: Opioid-Induced Hyperalgesia; Pain Care in Older Adults
Don’t Discount the Role of Diet for Chronic Pain Relief
Editorial: Why Haven’t There Been More Breakthrough Analgesics?
Gasping for Air: Sleep-Disordered Breathing and Chronic Opioids
How can botulinum toxin be used in chronic pain syndromes?
Inside the Potential of Peripheral Kappa Opioid Receptor Agonists
Neurodestructive Interventions for Cancer Pain
Obesity and Pain Care: Multifaceted Considerations for Treatment
Obesity and Rheumatoid Arthritis: What Clinicians Should Know
Sickle Cell Pain Crisis: Clinical Guidelines for the Use of Oxygen
The Complexity of Sickle Cell Pain: An Overview
The Perseverance Loop: The Psychology of Pain and Factors in Pain Perception
The Rapid Rise of Non-Opioid Pain Policies
Treating Pain by Overcoming Communication Barriers
Visual Artists Tackle What Pain Looks Like
Will 2020 Be the Year of Patient Education?

How can botulinum toxin be used in chronic pain syndromes?

What current research says on using botox for joint pain, pelvic pain, peripheral neuropathy, maxillofacial pain, and more.
Pages 16-18

Onabotulinum toxin-A (Botox) was FDA approved in 1991 for therapeutic use and later for cosmetic use. Subsequently, new products containing botulinum for medical and cosmetic uses were approved (Dysport, Myobloc, Xeomin). In 2019, prabotulinum toxin-A (Jeuveau) was approved for cosmetic use only.1 Botulinum toxin-A (BT) is FDA-approved for several medical indications listed in Table I and has been studied for other pain-related conditions.

Botulinum toxin is sourced from a bacterium called Clostridium botulinum. Its mechanism of action is essentially blocking neuromuscular transmission, which is achieved through binding and entering sites on nerve terminals on sympathetic or motor neurons and inhibiting acetylcholine release through cleaving SNAP-25. A protein, SNAP-25 is integral to acetylcholine docking and release from vesicles. After injection into a muscle, partial denervation occurs, reducing muscle movement in the local area. However, this can be reversed over time as the body may develop new axons leading to reinnervation of the muscle.2

Researchers concluded that botulinum toxin may be an option for short-term pain relief in those with refractory joint pain. (Image: iStock)

Osteoarthritis

Knee OA

More than 30 million Americans are estimated to be affected by osteoarthritis (OA), close to half of whom have symptomatic knee OA.3 Treatments for knee OA, as recommended by the American College of Rheumatology, include: acetaminophen, oral and topical NSAIDs, tramadol, and intra-articular injection of corticosteroids.4 BT was studied in 121 patients with knee OA in a double-blind, randomized trial. This study used a one-time dose of an intra-articular injection of BT at 200 IU versus placebo. Biomarkers studied included pressure pain thresholds and wind-up pain. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were used in the analysis, as were average daily pain (ADP), patient global impression of change (GIC), the painDETECT questionnaire (PD-Q), and rescue medication to assess clinical improvement. At Week 8, results showed statistically significant improvement for all WOMAC outcomes and pain scores. For Weeks 9 and 10, ADP improved significantly, and by Week 12 GIC improved significantly. There were also significant reductions in the need for use of rescue medication at Weeks 9 and 10.

Although this research supported the possibility of BT as a treatment of nociceptive pain in knee OA, more studies are needed to assess longer durations of treatment.5

Joint Pain

A 2018 meta-analysis evaluated use of intra-articular BT in patients with osteoarticular joint pain. Dosing in all studies was 100 units or 200 units of BT. Five of the six studies used a numeric rating scale (NRS) to measure pain (0 being no pain at all and 10 being maximal pain) and four of the five trials showed a positive effect on pain, irrespective of dose, at one or two months. One of the trials, however, found no significant difference in pain. The weighted mean difference in NRS between all five studies was −1.1, which was statistically significant. However, when evaluating the differences in dosing, high dosing (200 U) showed almost zero effect on pain scores while three out of the four studies with low dosing (100 U) showed significant results in regard to pain scores. Three trials re-evaluated the patients at six months to assess progress, and while their overall weighted mean NRS was lower, it was no longer statistically significant. Side effects associated with BT included flu-like symptoms, dry mouth, dizziness, and pain or swelling at the injection site. Researchers concluded that BT may be an option for short-term pain relief in those with refractory joint pain.6

Myofascial Pain

Myofascial pain is a condition in which pain is activated by pressure on different points in the muscles. This type of pain can be attributed to extensive use and repetition. Physical therapy is often warranted as well as medications to control pain.7 In 2014, a Cochrane review article evaluated BT and its use in myofascial pain syndromes from four randomized studies. Primary outcomes of the studies included pain intensity, frequency and duration of pain, relief from the pain, and pressure pain tolerance measured using visual analog scales (VAS) or categorical scales.

All studies included doses of BT that may be too low for pain relief, ranging from 5 to 50 units. However, in previous studies, higher doses (ie, up to 100 units) were associated with higher rates of adverse effects. Researchers concluded that the evidence was not sufficient to support the use of BT in patients with myofascial pain syndromes.8

Pelvic Muscle Pain

However, BT has been studied in patients specifically with myofascial pelvic pain. In one retrospective case series 50 women treated with BT had statistically reduced pain scores after treatment (3.7 ± 4.0 vs 6.4 ± 1.8), as well as a significant decrease in patients with trigger points, 44% vs 100%. Authors of the study noted that patients who were likely to have no improvement were those who had chronic bowel disorders.9

Peripheral Neuropathy

It is estimated that more than 20 million Americans have some form of peripheral neuropathy.10 According to the American Academy of Neurology, recommended treatments include anticonvulsants, antidepressants, and opioids for painful diabetic neuropathy; however, many of these therapies are limited by adverse effects.11 Botulinum toxin could be an additional option for treatment in these patients that is much needed to avoid opioid use. According to a study from 2015, opioids were prescribed first-line most frequently for diabetic peripheral neuropathy.12

Evidence suggests that BT injections may reduce pain intensity in patients with peripheral neuropathy. In a double-blind, randomized trial, the addition of BT statistically reduced intensity of pain over 24 weeks compared with placebo. Most patients who participated in this study had neuropathic pain stemming from post-traumatic events or post-surgical procedures. Dose per administration did not exceed 300 units, however; it varied between patients based on the size of the painful area. Drug administration was repeated at 12 weeks. Mean pain scores ranged from 6.5 at baseline to 4.6 at the 24-week mark based on the 11-point pain scale (0 - 10).13 A review was also conducted in 2018 that included 19 studies to evaluate the use of BT in central neuropathic pain. This included use in neuropathic pain after spinal cord injury, post-stroke shoulder pain, and multiple sclerosis specifically in detrusor overactivity and spasticity. Overall, they concluded that BT did have an effect on neuropathic pain and may be considered a treatment option.14

Maxillofacial Pain

Use of BT for pain-related conditions in the maxillofacial region has also expanded. Chronic facial pain due to masseter muscle hypertrophy associated with teeth clenching/grinding (eg, bruxism) or other jaw disorders may benefit from treatment with BT. Pain and tenderness associated with temporomandibular disorders (TMD) may improve with BT as an adjunctive therapy to other strategies or after conservative treatments have failed.15-17 However, not all studies of BT for TMD have shown benefit, and dosing has been inconsistent, ranging from 70 to 300 units. Most studies evaluated doses of 100 to 150 units.18

Although BT may offer a safe, less expensive option to surgical intervention, it has been associated with facial paralysis and dysphagia when studied for TMD.18 Use of BT may also improve quality of life in cancer and palliative care patients by reducing muscle spasticity and hypersecretions.15 Assessments have shown BT to be relatively safe with only temporary adverse effects such as dysphagia, muscle weakness, speech/articulation difficulties, injection-site tenderness, and flu-like symptoms noted.16 Inconsistent and/or one-time dosing, small sample sizes, and short duration of assessment limit current evidence. 

Risk of bias due  to study design and heterogeneity exists among studies. Well-designed, randomized clinical studies to overcome these limitations would help to further clarify the effectiveness of BT for many of these indications.16,18,19

 

Other Types of Chronic Pain and Risks

Botulinum toxin has also been evaluated for use in chronic anal fissure.20-22 Most studies assessing use of BT were not blinded. In addition, studies differed in dosing, site and number of injections which challenge the ability to establish recommendations for use.

Although BT has been shown to be helpful to treat pain in some populations it has not been well-studied across all populations. Botulinum toxin may cause fetal harm in pregnancy based on data gathered from animal studies. It is also unknown whether BT is present in breast milk so risk–benefit analysis should be considered. Pediatric patients have limited safety and efficacy data based on age and disease state it is being used to treat. Per the FDA labeling, efficacy and safety have not been proven in patients less than 18 years old for chronic migraine, detrusor overactivity, spasticity, and axillary hyperhidrosis. Patients under 16 do not have proven efficacy or safety for treatment of cervical dystonia, and those under 12 years of age are not supported for use in blepharospasm or strabismus.2 Adverse effects of BT are specific to the indication for use, however a few of them include headache, flu-like symptoms, and pain at the injection site.23

Additional research is essential to support adjunctive therapy or treatment with BT for various chronic pain conditions. Although studies may show benefit, it is important to consider that dosing and long-term efficacy have not been well-established for many of these conditions.

Last updated on: February 4, 2020
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