Botulinum Toxin in Pain Management

  • Author: Heather Rachel Davids, MD; Chief Editor: Consuelo T Lorenzo, MD  more...
Updated: Mar 09, 2016


Diagnosis and treatment of painful muscle syndromes can be a difficult and frustrating task for any clinician. Typically, the mainstay of therapy for such conditions is therapeutic exercise, analgesics, and a tincture of time. Unfortunately, not all patients respond to this paradigm, and, despite heroic efforts on the part of the treating clinician, some conditions are refractory to this approach.

Reports have described the purported effectiveness of using a biologic neuromuscular blocking agent, botulinum toxin, in the treatment of painful conditions associated with skeletal muscle. While incompletely understood and at times controversial, use of botulinum toxin in the treatment of conditions associated with involuntary muscle contraction, such as focal dystonia and spasticity, is supported by prospective, randomized clinical research; however, while the volume of comparable studies in pain syndromes is growing, the number of clinical randomized trials is limited. Moreover, not all such reports have demonstrated clear efficacy of the use of botulinum toxin under all circumstances. Therefore, in view of our current understanding of the nature of muscle-induced pain and the paucity of prospective research regarding neuromuscular blockade and/or inhibition of nociception in such conditions, critical and careful analysis of the data and opinions presented in this section is appropriate.

This article provides general direction and practical details for the clinician considering botulinum toxin for treatment of pain. Anatomic drawings for injection localization and dosing information are intended only as general guidelines; therapy with botulinum toxin always must be individualized, accounting for the patient's needs and the clinician's expertise. In addition, information presented should be used as a convenient reference source, not as a substitute for clinical training in the use of botulinum toxin.

For excellent patient education resources, see eMedicineHealth's patient education articles BOTOX® Injections and Chronic Pain.


Pharmacology of Botulinum Toxin


Botulinum toxin is produced by the anaerobic bacterium Clostridium botulinum, a rod-shaped, gram-positive organism found in soil and water. Botulinum toxin type A (abbreviated BoNT-A or BTX-A) belongs to a family of neurotoxins (designated as types A, B, C1, C2, D, E, F, and G) with similar properties. BoNT-A causes degrees of flaccid (rather than rigid or tetanic) paralysis by blocking acetylcholine, required for muscle contraction, from release at the nerve terminal.[1, 2, 3] Therapeutic benefit may be derived by exploiting the pharmacologic properties of carefully administered regional application of this purified neurotoxin.

The various botulinum toxins possess individual potencies, and care is required to assure proper use and avoid medication errors. Recent changes to the established drug names by the FDA were intended to reinforce these differences and prevent medication errors. The products and their approved indications include the following:

  • OnabotulinumtoxinA (Botox, Botox Cosmetic)
    • Botox - Cervical dystonia, severe primary axillary hyperhidrosis, strabismus, blepharospasm
    • Botox Cosmetic - Moderate-to-severe glabellar lines
  • AbobotulinumtoxinA (Dysport) - Cervical dystonia, moderate-to-severe glabellar lines
  • IncobotulinumtoxinA (Xeomin) - Cervical dystonia, blepharospasm
  • RimabotulinumtoxinB (Myobloc) - Cervical dystonia

Botulinum toxin's putative success in pain management was originally attributed to its ability to block acetylcholine from being released at the synapse. One important feature of botulinum toxin in pain treatment is that the neurotoxin is thought to act only on motor nerve endings while sparing sensory nerve fibers from its effects. Subsequently, however, effects of botulinum toxin on nociceptive neurons were demonstrated in preclinical studies.[4, 5, 6, 7] Thus, analgesic effects are likely to occur, but not as a consequence of blocking afferent sensory fibers at the site of injection; rather, they have been attributed to secondary effects that may be the result of muscle paralysis, improved blood flow, the release of nerve fibers under compression by abnormally contracting muscle, and, perhaps more importantly, the effects of the toxin on nociceptive neurons.

Median lethal dose (LD50)

Botulinum toxin's median lethal dose (LD50) has been determined across several animal species but not in humans. A unit of BoNT-A usually is defined in terms of its biologic potency. One mouse unit (MU) of BoNT-A equals the LD50 for a 20-g Swiss-Webster mouse. Yet BoNT-A sensitivity varies among different species. LD50 in monkeys has been determined as 39 U/kg. Based on these findings from primate studies, human LD50 is estimated at approximately 3000 U for a 70-kg adult. Typical doses for larger muscle groups range from 60-400 total units given in a single treatment; however, because of inadequate understanding of the complete dose response curve in humans, a relative ceiling dose of 360 U, given no sooner than 12 weeks apart, is recommended.

Adverse effects

Since the mechanism of action of BoNT-A is so specific, adverse effects are uncommon and systemic effects rare. Flulike syndrome has been reported, but it is generally short-lived. Other adverse effects have been reported, but they are not necessarily a result of BoNT-A treatment. They include muscle soreness, headaches, light-headedness, fever, chills, hypertension, weakness, diarrhea, and abdominal pain.

Muscular weakness, the predominant and desirable effect of botulinum toxin injection, also may be considered an adverse effect when weakness occurs in an unintended area or is greater than intended. Clinicians must understand the functional consequences of unintended weakness caused by botulinum toxin injection. While overweakening the muscles that curl the toes may have few, if any, undesirable consequences, spread of toxin into the muscles that control swallowing, which can occur when injecting muscles near the larynx (for instance, the proximal part of the sternocleidomastoid muscle), may result in difficulty swallowing. Patients, therefore, should be informed of the potential for either too much weakness in the injected area or weakness in nearby muscles.


Use of Botulinum Toxin in Painful Neuromuscular Disorders

Previous studies of conditions with involuntary muscular contractions have provided some indirect evidence of the analgesic effects of botulinum toxin. A summary of a MEDLINE search for clinical studies with the headings "botulinum toxin," and "pain" performed from 1966 to September 2005 resulted in more than 40 studies that included "pain" within the article title or abstract.

In the report, pain response to treatment with botulinum toxin was cited within the context of treatment for a number of conditions, including tennis elbow, chronic anal fissure, pain attributed to mastectomy and hemorrhoidectomy, headaches (including migraine), piriformis syndrome, facial pain, myofascial pain, temporomandibular joint syndrome (TMJ), low back pain, chronic prostatic pain, and whiplash.[8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24]

Variables in these studies included dosing, concentration, injection techniques, use of concurrent therapeutic modalities, varying diagnoses, and chronicity of neurologic dysfunction. Some patients treated for disorders that included involuntary muscle contraction (eg, dystonia) also reported benefits in pain reduction in muscles injected with botulinum toxin. Variables in the studies cited included the presence or absence of concurrent therapy, diagnoses, length of time since onset of pain, dosing and concentration, and methodology for measurement of outcome.[25]  In 2016, the US Food and Drug Administration approved onabotulinumtoxinA to decrease the severity of stiffness in ankle and toe muscles among adults with lower limb spasticity.[26]

Another review of botulinum toxin studies was performed by the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.[27] Evidence of the toxin's effectiveness was examined for a variety of conditions, including chronic tension-type headache, episodic migraine, chronic daily migraine, and chronic low back pain.

According to the subcommittee's report, the evidence indicated that botulinum toxin may be useful in the treatment of lower back pain but that it is probably not effective against episodic migraine and chronic tension-type headache. The report also stated that the available evidence was not strong or consistent enough to determine botulinum toxin's usefulness in the treatment of chronic daily headache (primarily, transformed migraine).

A German report also investigated botulinum toxin's effectiveness against tension-type headache.[28] In a double-blind, randomized, placebo-controlled study, researchers compared the number of headache-free days experienced by patients 4 weeks prior to injections of BoNT-A with the number of such days occurring 4-8 weeks after treatment. The number of headache-free days increased for the study's placebo and nonplacebo groups, but the difference in increase between the 2 groups was not significant.

The researchers did find, however, that in comparison with the placebo group, the patients who received BoNT-A injections experienced a significant reduction in the duration of their headaches.

A study by Naik et al reported that the use of botulinum toxin to treat painful cutaneous leiomyomas was associated with improved quality of life and with a trend toward improved pain at rest.[29]


Botulinum Toxin and Myofascial Pain

Many therapies are available to patients with myofascial pain syndrome. Much of the variation in forms of treatment (and diagnoses) of this disorder probably results from differences in culture, training, and recognition of an often undiagnosed syndrome of pain, dysfunction, and autonomic dysregulation. The etiology of myofascial pain syndrome associated with trigger points is incompletely understood. Some clinicians believe that it characteristically results from either an acute episode of muscle overload or from chronic and/or repetitive muscle overload. Active myofascial trigger points (MTrPs), which cause pain, exhibit marked localized tenderness and often refer pain to distant sites and disturb motor function. In addition, MTrPs may produce autonomic changes.

For clinical identification of MTrPs, the clinician palpates a localized tender spot in a nodular portion of a taut ropelike band of muscle fibers. Pressure over a trigger point elicits pain at that area and also may elicit pain at a site distant from the point under the fingertip (in a phenomenon known as referred pain). Upon palpation, MTrPs also elicit pain that mirrors the patient's experience. Applied pressure often evokes from the patient the response, "That's my pain!" Insertion of a needle, abrupt palpation, or even a brisk tap with the fingertip directly over the trigger point may result in a brief muscle contraction that is detectable by the examiner. This rapid contraction of muscle fibers of the ropelike taut band is termed a local twitch response.

In muscles that move a relatively small mass or are large and superficial (eg, finger extensors, gluteus maximus), the response is seen easily and may cause the limb to jump when the examiner introduces a needle into the trigger point. Localized abnormal response from the autonomic nervous system may cause piloerection, localized sweating, or regional temperature changes in the skin, attributed to altered blood flow.

Injection of muscles with botulinum toxin has been reported to be effective for myofascial pain caused by trigger points (TrPs) in a few small prospective studies. However, strong evidence of efficacy in larger, multicenter trials is lacking.[8, 30, 31]


Botulinum Toxin and the Muscle Spindle: Clinical Issues

Little evidence exists that painful muscle areas, such as TrPs, are associated with structural change or sensory structures, such as the muscle spindle; however, the spindle is intimately involved in certain conditions of abnormal muscle activity. In the spastic condition, for example, the stretch reflex is enhanced for a variety of reasons, such as lack of inhibition from spinal cord interneurons. Whatever the reason, muscle spindle physiology is an important regulator of muscle tone in the spastic condition.

BoNT-A has been recognized to reduce pain associated with various clinical conditions, including craniocervical dystonia, tension headaches, cervicogenic headaches, and migraine, an effect that has been observed independently of the toxin's effect on muscle relaxation. (As stated above, however, controversy exists regarding botulinum toxin's effectiveness in the treatment of headache.)[27, 28, 32, 33, 34, 35, 36]

Importantly, BoNT-A has been shown to inhibit release of neurotransmitters involved in pain transmission, including glutamate and substance P in rats. A formalin-induced pain model in rats has helped to show that a local peripheral injection of BoNT-A can significantly reduce glutamate release, signs of pain, and local edema without inducing muscle weakness. These preclinical observations have yet to be definitively confirmed in human patients; however, they provide a possible rationale for BoNT-A's use in chronic painful conditions, including chronic myofascial pain syndromes.


When to Consider Botulinum Toxin

Indications for botulinum treatment are not entirely clear for patients with myofascial pain syndrome. These patients may be considered candidates for botulinum toxin if they have not responded to traditional forms of treatment, have had a chronic refractory problem for 3 months or longer, have had a complete medical workup to rule out other nonmuscular causes for their pain, and have clearly defined TrPs.

The clinician should proceed with caution before considering using botulinum toxin in the treatment of a patient with myofascial pain. Remember that use of BoNT-A for the treatment of pain is only approved in the United States for pain related to cervical dystonia. Use of BoNT-A for myofascial pain, therefore, is an off-label use and may be considered most appropriate only for patients with a condition that does not respond to, or is judged inappropriate for, more conservative treatment. Factors that may identify a myofascial pain syndrome as potentially responding favorably to botulinum toxin injections include muscle hypertrophy, neurogenic and/or vascular compression, anatomic localization that isolates the target muscle from other structures, and more than 1 outcome measure to determine the efficacy of treatment. One such condition that meets these criteria is termed piriformis muscle syndrome (PMS).


Botulinum Toxin Use in Piriformis Muscle Syndrome

PMS is a controversial myofascial pain condition that presents with seemingly bizarre symptoms. Patients typically are female, have a recent history of trauma to the buttocks or pelvis (usually from a fall), and complain of deep pain in the buttocks and hip, radiating into the thigh or even into the leg and foot. These characteristic signs and symptoms may be from sciatic nerve compression by a contracted piriformis muscle as the nerve passes through the pelvis. Although some clinicians believe this diagnosis is controversial, several peer-reviewed articles cite clinical, anatomic, and electrophysiologic evidence for this distinct condition causing low back and leg pain.

On clinical examination, pressure over the buttocks at a point midway between the sacrum and greater trochanter of the hip reproduces the patient's pain complaint. Since the piriformis muscle is so deep, some clinicians say that palpation of this TrP can be performed properly only by rectal or vaginal examination. Palpation of the TrP on the posterolateral portion of the rectal (or vaginal) vault elicits pain at the site of compression and refers pain either into the thigh or down the leg.

The Beatty maneuver (see image below) also is a helpful clinical method of reproducing the patient's pain in this condition.[37] The patient is asked to lie on the nonpainful side and abduct the thigh by moving the painful leg off the table. This maneuver effectively contracts the piriformis muscle and should reproduce the patient's pain in the buttocks; however, since the syndrome essentially causes sciatic nerve compression at the level of the hip, other causes of sciatica should be ruled out (eg, herniated lumbar disc).

The Beatty maneuver. The Beatty maneuver.

One helpful diagnostic aid is electromyography. In a patient with radiculopathy and sciatica, an electromyographic examination should reveal abnormal spontaneous electrical activity in the extensor muscles of the back. In piriformis syndrome, the electromyogram (EMG) is classically normal. If there is enough sciatic nerve compression to cause axon loss, the abnormalities should be in the muscles distal to the piriformis, and no electrical activity should be seen in the back muscles. A special nerve conduction test, H reflex, has been reported to demonstrate abnormalities in piriformis syndrome when abduction, internal rotation, and flexion of the thigh compress the sciatic nerve; however, this result has not been reproduced by other clinicians. Making a reliable diagnosis in piriformis syndrome is almost impossible; thus, treatment also is difficult.

In some patients, if conservative treatment of piriformis syndrome fails, local injections of anesthetics and/or steroids should be considered. Surgical resection of the piriformis muscle is an additional option; however, some patients may gain short-term benefits from local TrP injections into the muscle without responding to other treatment for long-term pain control. This subset of patients may benefit from treatment with BoNT-A. (See image below.)

Left piriformis muscle, posterior view. Inject 100 Left piriformis muscle, posterior view. Inject 100 U botulinum toxin type A (BOTOX®) diluted in 3 mL saline into the area marked with an 'X' when guided by fluoroscopy.

A limited number of studies assess the efficacy of botulinum toxin in the treatment of piriformis syndrome.[8] For example, Childers and colleagues reported findings from a double-blind placebo-controlled crossover pilot study of BoNT-A injection for refractory piriformis syndrome in 9 subjects.[38] All patients in this study reported pain intensity greater than 3/10 on visual analog pain scales (VASs) after at least 3 months of failed conservative treatment for PMS prior to enrollment. Symptomatic muscle in each patient was injected with 100 U BoNT-A or placebo (saline), using fluoroscopic and electromyographic guidance. Ten weeks later, saline or BoNT-A injections were repeated. The main outcome measures were VAS of pain intensity, distress, spasm, and interference with daily activities.

At baseline, no differences were detected between groups, yet significant (P < .05) differences were observed between the average of 2 minimum VAS at baseline and the average of 2 minimum VAS (in all categories) under the 10-week treatment (BoNT-A) arm, but not the 10-week placebo arm. In addition, BoNT-A treatment average was improved significantly (P = .0273), from baseline/washout average in VAS of daily activities. Data also suggested that a significant (P = .0547) improvement in VAS in muscle spasm (P = .0547) occurred in the BoNT-A group but not in the placebo group. Taken together, these findings demonstrated that, compared to intramuscular saline, BoNT-A injections reduced some, but not all, reports of pain attributed to chronic PMS.


Injection Methods

Therapy with botulinum toxin should be individualized for the patient and the clinician. The equipment needs should be determined according to the needs of the patient, the clinician's training, and the anatomic target for injection. For example, treatments for blepharospasm usually are given by simple subcutaneous injections around the eye without the use of special equipment; however, injections into the deep compartments of the low back, such as the psoas major muscle compartment, may require the use of special imaging techniques.

A 1.0 mL tuberculin-type syringe with 5/8-inch 25-gauge needle is adequate for superficial muscles. For small muscles (eg, facial muscles), a 1-inch 30-gauge needle is sufficient. For larger muscles, such as the hamstrings, a 1-inch or 1.5-inch 25-gauge needle is adequate.

For most limb muscles, the use of electromyography or motor point stimulation (e-stim) is recommended to identify muscles, particularly the smaller muscles in the forearm. For example, a commonly injected finger flexor muscle, the flexor digitorum sublimis (FDS), is nearly impossible to locate without electromyographic guidance. For the clinician who is developing his or her skills in identifying specific muscles for injection with botulinum toxin, the use of simple, audio-only electromyography may enhance the clinician's understanding of functional anatomy and aid the clinician in making decisions on injection localization. For muscles requiring electromyographic guidance, a cannulated monopolar needle cathode, through which botulinum toxin can be injected, is used. Surface reference (anode) and ground electrodes should be placed near the cathode needle.

After placing the patient in a position where the desired muscle can be relaxed, the motor point should be located. Botulinum toxin then can be given after aspiration to prevent intravascular injection. Alcohol, if used to clean the skin, should be allowed to dry completely to prevent toxin deactivation. The use of operating rooms or special procedure (sterile) rooms equipped with monitoring devices for the purpose of intramuscular injections using small caliber needles is not necessary. Most patients can be treated safely in an office setting by experienced clinicians.

Postinjection Follow-up

If any discomfort or pain occurs over 24-48 hours after injection, muscle relaxants or acetaminophen may be given. Stronger analgesics usually are not required.

Contributor Information and Disclosures

Heather Rachel Davids, MD Physician, Department of Anesthesiology, Interventional Pain Medicine, University of Colorado Health Sciences Center

Heather Rachel Davids, MD is a member of the following medical societies: American Academy of Pain Medicine, American Academy of Physical Medicine and Rehabilitation, Association of Academic Physiatrists

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Michael T Andary, MD, MS Professor, Residency Program Director, Department of Physical Medicine and Rehabilitation, Michigan State University College of Osteopathic Medicine

Michael T Andary, MD, MS is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Association of Neuromuscular and Electrodiagnostic Medicine, American Medical Association, Association of Academic Physiatrists

Disclosure: Received honoraria from Allergan for speaking and teaching.

Chief Editor

Consuelo T Lorenzo, MD Medical Director, Senior Products, Central North Region, Humana, Inc

Consuelo T Lorenzo, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation

Disclosure: Nothing to disclose.

Additional Contributors

Rajesh R Yadav, MD Associate Professor, Section of Physical Medicine and Rehabilitation, MD Anderson Cancer Center, University of Texas Medical School at Houston

Rajesh R Yadav, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation

Disclosure: Nothing to disclose.


Martin K Childers, DO, PhD Professor, Department of Neurology, Wake Forest University School of Medicine; Professor, Rehabilitation Program, Institute for Regenerative Medicine, Wake Forest Baptist Medical Center

Martin K Childers, DO, PhD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Congress of Rehabilitation Medicine, American Osteopathic Association, Christian Medical & Dental Society, and Federation of American Societies for Experimental Biology

Disclosure: Allergan pharma Consulting fee Consulting

  1. Coffield JA, Considine RB, Simpson LL. The site and mechanism of action of botulinum neurotoxin. Jankovic J, Hallett M, eds. Therapy With Botulinum Toxin. New York, NY: Marcel Dekker; 1994. 3-14.

  2. Melling J, Hambleton P, Shone CC. Clostridium botulinum toxins: nature and preparation for clinical use. Eye. 1988. 2 ( Pt 1):16-23. [Medline].

  3. Sellin LC. The action of botulinum toxin at the neuromuscular junction. Med Biol. 1981 Feb. 59(1):11-20. [Medline].

  4. Arezzo JC. Possible mechanisms for the effects of botulinum toxin on pain. Clin J Pain. 2002 Nov-Dec. 18(6 Suppl):S125-32. [Medline].

  5. Blersch W, Schulte-Mattler WJ, Przywara S, et al. Botulinum toxin A and the cutaneous nociception in humans: a prospective, double-blind, placebo-controlled, randomized study. J Neurol Sci. 2002 Dec 15. 205(1):59-63. [Medline].

  6. Mense S. Neurobiological basis for the use of botulinum toxin in pain therapy. J Neurol. 2004 Feb. 251 Suppl 1:I1-7. [Medline].

  7. Aoki KR. Evidence for antinociceptive activity of botulinum toxin type A in pain management. Headache. 2003 Jul-Aug. 43 Suppl 1:S9-15. [Medline].

  8. Jeynes LC, Gauci CA. Evidence for the use of botulinum toxin in the chronic pain setting--a review of the literature. Pain Pract. 2008 Jul-Aug. 8(4):269-76. [Medline].

  9. Colak T, Ipek T, Kanik A, Aydin S. A randomized trial of botulinum toxin vs lidocain pomade for chronic anal fissure. Acta Gastroenterol Belg. 2002 Oct-Dec. 65(4):187-90. [Medline].

  10. Davies J, Duffy D, Boyt N, et al. Botulinum toxin (botox) reduces pain after hemorrhoidectomy: results of a double-blind, randomized study. Dis Colon Rectum. 2003 Aug. 46(8):1097-102. [Medline].

  11. Freund B, Schwartz M, Symington JM. Botulinum toxin: new treatment for temporomandibular disorders. Br J Oral Maxillofac Surg. 2000 Oct. 38(5):466-71. [Medline].

  12. Freund BJ, Schwartz M. Relief of tension-type headache symptoms in subjects with temporomandibular disorders treated with botulinum toxin-A. Headache. 2002 Nov-Dec. 42(10):1033-7. [Medline].

  13. Girdler NM. Use of botulinum toxin to alleviate facial pain. Br J Hosp Med. 1994 Oct 5-18. 52(7):363. [Medline].

  14. Godevenos D, Pikoulis E, Pavlakis E, et al. The treatment of chronic anal fissure with botulinum toxin. Acta Chir Belg. 2004 Oct. 104(5):577-80. [Medline].

  15. Johnstone SJ, Adler CH. Headache and facial pain responsive to botulinum toxin: an unusual presentation of blepharospasm. Headache. 1998 May. 38(5):366-8. [Medline].

  16. Layeeque R, Hochberg J, Siegel E, et al. Botulinum toxin infiltration for pain control after mastectomy and expander reconstruction. Ann Surg. 2004 Oct. 240(4):608-13; discussion 613-4. [Medline]. [Full Text].

  17. Minguez M, Melo F, Espi A, et al. Therapeutic effects of different doses of botulinum toxin in chronic anal fissure. Dis Colon Rectum. 1999 Aug. 42(8):1016-21. [Medline].

  18. Nixdorf DR, Heo G, Major PW. Randomized controlled trial of botulinum toxin A for chronic myogenous orofacial pain. Pain. 2002 Oct. 99(3):465-73. [Medline].

  19. von Lindern JJ. Type A botulinum toxin in the treatment of chronic facial pain associated with temporo-mandibular dysfunction. Acta Neurol Belg. 2001 Mar. 101(1):39-41. [Medline].

  20. von Lindern JJ, Niederhagen B, Bergé S, et al. Type A botulinum toxin in the treatment of chronic facial pain associated with masticatory hyperactivity. J Oral Maxillofac Surg. 2003 Jul. 61(7):774-8. [Medline].

  21. Wollina U, Konrad H. Botulinum toxin A in anal fissures: a modified technique. J Eur Acad Dermatol Venereol. 2002 Sep. 16(5):469-71. [Medline].

  22. Sun SF, Hsu CW, Lin HS, Chou YJ, Chen JY, Wang JL. Efficacy of intraarticular botulinum toxin A and intraarticular hyaluronate plus rehabilitation exercise in patients with unilateral ankle osteoarthritis: a randomized controlled trial. J Foot Ankle Res. 2014 Feb 6. 7(1):9. [Medline]. [Full Text].

  23. Bernhard MK, Bertsche A, Syrbe S, Weise S, Merkenschlager A. [Botulinum toxin injections for chronic migraine in adolescents - an early therapeutic option in the transition from neuropaediatrics to neurology]. Fortschr Neurol Psychiatr. 2014 Jan. 82(1):39-42. [Medline].

  24. Mitrovic J, Prka Z, Zic R, Marusic S, Morovic-Vergles J. Focal Myositis of Lower Extremity Responsive to Botulinum A Toxin. Clin Neuropharmacol. 2014 Mar 7. [Medline].

  25. Schilder JC, van Dijk JG, Dressler D, Koelman JH, Marinus J, van Hilten JJ. Responsiveness to botulinum toxin type A in muscles of complex regional pain patients with tonic dystonia. J Neural Transm. 2014 Feb 15. [Medline].

  26. Anderson P. FDA Approves Botox for Lower Limb Spasticity. Medscape Medical News. Available at January 26, 2016; Accessed: March 10, 2016.

  27. Naumann M, So Y, Argoff CE, et al. Assessment: botulinum neurotoxin in the treatment of autonomic disorders and pain (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2008 May 6. 70(19):1707-14. [Medline].

  28. Straube A, Empl M, Ceballos-Baumann A, et al. Pericranial injection of botulinum toxin type A (Dysport) for tension-type headache - a multicentre, double-blind, randomized, placebo-controlled study. Eur J Neurol. 2008 Mar. 15(3):205-13. [Medline].

  29. Naik HB, Steinberg SM, Middelton LA, Hewitt SM, Zuo RC, Linehan WM, et al. Efficacy of Intralesional Botulinum Toxin A for Treatment of Painful Cutaneous Leiomyomas: A Randomized Clinical Trial. JAMA Dermatol. 2015 Oct. 151 (10):1096-102. [Medline].

  30. Guarda-Nardini L, Stecco A, Stecco C, Masiero S, Manfredini D. Myofascial pain of the jaw muscles: comparison of short-term effectiveness of botulinum toxin injections and fascial manipulation technique. Cranio. 2012 Apr. 30(2):95-102. [Medline].

  31. Gerwin R. Botulinum toxin treatment of myofascial pain: a critical review of the literature. Curr Pain Headache Rep. 2012 Oct. 16(5):413-22. [Medline].

  32. Mathew NT. Dynamic optimization of chronic migraine treatment: current and future options. Neurology. 2009 Feb 3. 72(5 Suppl):S14-20. [Medline].

  33. Obermann M, Diener HC. Is botulinum toxin useful in treating headache? No. Curr Treat Options Neurol. 2009 Jan. 11(1):24-31. [Medline].

  34. Ashkenazi A, Silberstein S. Is botulinum toxin useful in treating headache? Yes. Curr Treat Options Neurol. 2009 Jan. 11(1):18-23. [Medline].

  35. Aguggia M. Treating headaches with botulinum toxin. Neurol Sci. 2008 May. 29 Suppl 1:S137-9. [Medline].

  36. Frampton JE. OnabotulinumtoxinA (BOTOX®): a review of its use in the prophylaxis of headaches in adults with chronic migraine. Drugs. 2012 Apr 16. 72(6):825-45. [Medline].

  37. Beatty RA. The piriformis muscle syndrome: a simple diagnostic maneuver. Neurosurgery. 1994 Mar. 34(3):512-4; discussion 514. [Medline].

  38. Childers MK, Wilson DJ, Gnatz SM, et al. Botulinum toxin type A use in piriformis muscle syndrome: a pilot study. Am J Phys Med Rehabil. 2002 Oct. 81(10):751-9. [Medline].

  39. Acquadro MA, Borodic GE. Treatment of myofascial pain with botulinum A toxin. Anesthesiology. 1994 Mar. 80(3):705-6. [Medline].

  40. Aurora SK, Gawel M, Brandes JL, et al. Botulinum toxin type a prophylactic treatment of episodic migraine: a randomized, double-blind, placebo-controlled exploratory study. Headache. Apr 2007. 47(4):486-99. [Medline].

  41. Barwood S, Baillieu C, Boyd R, et al. Analgesic effects of botulinum toxin A: a randomized, placebo-controlled clinical trial. Dev Med Child Neurol. 2000 Feb. 42(2):116-21. [Medline].

  42. Bickerton LE, Agur AM, Ashby P. Flexor digitorum superficialis: locations of individual muscle bellies for botulinum toxin injections. Muscle Nerve. 1997 Aug. 20(8):1041-3. [Medline].

  43. Binder WJ, Brin MF, Blitzer A, et al. Botulinum toxin type A (BOTOX) for treatment of migraine headaches: an open-label study. Otolaryngol Head Neck Surg. 2000 Dec. 123(6):669-76. [Medline].

  44. Borodic GE, Acquadro M, Johnson EA. Botulinum toxin therapy for pain and inflammatory disorders: mechanisms and therapeutic effects. Expert Opin Investig Drugs. 2001 Aug. 10(8):1531-44. [Medline].

  45. Borodic GE, Ferrante R, Pearce LB, et al. Histologic assessment of dose-related diffusion and muscle fiber response after therapeutic botulinum A toxin injections. Mov Disord. 1994 Jan. 9(1):31-9. [Medline].

  46. Cheshire WP, Abashian SW, Mann JD. Botulinum toxin in the treatment of myofascial pain syndrome. Pain. 1994 Oct. 59(1):65-9. [Medline].

  47. Childers MK. Rationale for injection procedures for botulinum toxin type A in skeletal limb muscles. Eur J Neurol. 1997. 4(Suppl 2):37-40.

  48. da Silva LB, Kulas D, Karshenas A, Cairns BE, Bach FW, Arendt-Nielsen L, et al. Time course analysis of the effects of botulinum neurotoxin type A on pain and vasomotor responses evoked by glutamate injection into human temporalis muscles. Toxins (Basel). 2014 Feb 10. 6(2):592-607. [Medline]. [Full Text].

  49. De Andrés J, Cerda-Olmedo G, Valía JC, et al. Use of botulinum toxin in the treatment of chronic myofascial pain. Clin J Pain. 2003 Jul-Aug. 19(4):269-75. [Medline].

  50. de Paiva A, Ashton AC, Foran P, et al. Botulinum A like type B and tetanus toxins fulfils criteria for being a zinc-dependent protease. J Neurochem. 1993 Dec. 61(6):2338-41. [Medline].

  51. Fishman LM, Anderson C, Rosner B. BOTOX and physical therapy in the treatment of piriformis syndrome. Am J Phys Med Rehabil. 2002 Dec. 81(12):936-42. [Medline].

  52. Fishman LM, Zybert PA. Electrophysiologic evidence of piriformis syndrome. Arch Phys Med Rehabil. 1992 Apr. 73(4):359-64. [Medline].

  53. Foster L, Clapp L, Erickson M, et al. Botulinum toxin A and chronic low back pain: a randomized, double-blind study. Neurology. 2001 May 22. 56(10):1290-3. [Medline].

  54. Freund B, Schwartz M. Temporal relationship of muscle weakness and pain reduction in subjects treated with botulinum toxin A. J Pain. 2003 Apr. 4(3):159-65. [Medline].

  55. Freund BJ, Schwartz M. Treatment of whiplash associated neck pain [corrected] with botulinum toxin-A: a pilot study. J Rheumatol. 2000 Feb. 27(2):481-4. [Medline].

  56. Fricton JR. Myofascial pain syndrome. Neurol Clin. 1989 May. 7(2):413-27. [Medline].

  57. Gandhavadi B. Bilateral piriformis syndrome associated with dystonia musculorum deformans. Orthopedics. 1990 Mar. 13(3):350-1. [Medline].

  58. Girdler NM. Uses of botulinum toxin. Lancet. 1997 Mar 29. 349(9056):953. [Medline].

  59. Göbel H, Heinze A, Heinze-Kuhn K, et al. Botulinum toxin A in the treatment of headache syndromes and pericranial pain syndromes. Pain. 2001 Apr. 91(3):195-9. [Medline].

  60. Hallin RP. Sciatic pain and the piriformis muscle. Postgrad Med. 1983 Aug. 74(2):69-72. [Medline].

  61. Hayton MJ, Santini AJ, Hughes PJ, et al. Botulinum toxin injection in the treatment of tennis elbow. A double-blind, randomized, controlled, pilot study. J Bone Joint Surg Am. 2005 Mar. 87(3):503-7. [Medline].

  62. Hesse S, Jahnke MT, Luecke D, et al. Short-term electrical stimulation enhances the effectiveness of Botulinum toxin in the treatment of lower limb spasticity in hemiparetic patients. Neurosci Lett. 1995 Dec 1. 201(1):37-40. [Medline].

  63. Jankiewicz JJ, Hennrikus WL, Houkom JA. The appearance of the piriformis muscle syndrome in computed tomography and magnetic resonance imaging. A case report and review of the literature. Clin Orthop. 1991 Jan. (262):205-9. [Medline].

  64. Jankovic J, Brin MF. Therapeutic uses of botulinum toxin. N Engl J Med. 1991 Apr 25. 324(17):1186-94. [Medline].

  65. Julsrud ME. Piriformis syndrome. J Am Podiatr Med Assoc. 1989 Mar. 79(3):128-31. [Medline].

  66. Keizer SB, Rutten HP, Pilot P, et al. Botulinum toxin injection versus surgical treatment for tennis elbow: a randomized pilot study. Clin Orthop Relat Res. 2002 Aug. 125-31. [Medline].

  67. King JC, Goddard MJ. Pain rehabilitation. 2. Chronic pain syndrome and myofascial pain. Arch Phys Med Rehabil. 1994 May. 75(5 Spec No):S9-14. [Medline].

  68. LaBan MM, Meerschaert JR, Taylor RS. Electromyographic evidence of inferior gluteal nerve compromise: an early representation of recurrent colorectal carcinoma. Arch Phys Med Rehabil. 1982 Jan. 63(1):33-5. [Medline].

  69. Lalli F, Gallai V, Tambasco N, et al. Botulinum A toxin versus lidocaine in the treatment of myofascial pain: a double-blind randomized study. International Conference 1999: Basic and Therapeutic Aspects of Botulinum and Tetanus Toxins. 1999. 72:

  70. Lang AM. Botulinum toxin therapy for myofascial pain disorders. Curr Pain Headache Rep. 2002 Oct. 6(5):355-60. [Medline].

  71. Lang AM. Botulinum toxin type A therapy in chronic pain disorders. Arch Phys Med Rehabil. 2003 Mar. 84(3 Suppl 1):S69-73; quiz S74-5. [Medline].

  72. Lang AM. Botulinum toxin type B in piriformis syndrome. Am J Phys Med Rehabil. 2004 Mar. 83(3):198-202. [Medline].

  73. McClaflin RR. Myofascial pain syndrome. Primary care strategies for early intervention. Postgrad Med. 1994 Aug. 96(2):56-9, 63-6, 69-70 passim. [Medline].

  74. Mellanby J. Comparative activities of tetanus and botulinum toxins. Neuroscience. 1984 Jan. 11(1):29-34. [Medline].

  75. Monsivais JJ, Monsivais DB. Botulinum toxin in painful syndromes. Hand Clin. 1996 Nov. 12(4):787-9. [Medline].

  76. Moore AP, Wood GD. The medical management of masseteric hypertrophy with botulinum toxin type A. Br J Oral Maxillofac Surg. 1994 Feb. 32(1):26-8. [Medline].

  77. National Institutes of Health. Consensus conference. Clinical use of botulinum toxin. National Institutes of Health. Conn Med. 1991 Aug. 55(8):471-7. [Medline].

  78. Noftal F. The piriformis syndrome. Can J Surg. 1988 Jul. 31(4):210. [Medline].

  79. Ojala T, Arokoski JP, Partanen J. The effect of small doses of botulinum toxin a on neck-shoulder myofascial pain syndrome: a double-blind, randomized, and controlled crossover trial. Clin J Pain. 2006 Jan. 22(1):90-6. [Medline].

  80. Pacchetti C, Albani G, Martignoni E, et al. "Off" painful dystonia in Parkinson''s disease treated with botulinum toxin. Mov Disord. 1995 May. 10(3):333-6. [Medline].

  81. Padberg M, de Bruijn SF, de Haan RJ, et al. Treatment of chronic tension-type headache with botulinum toxin: a double-blind, placebo-controlled clinical trial. Cephalalgia. 2004 Aug. 24(8):675-80. [Medline].

  82. Papadopoulos SM, McGillicuddy JE, Albers JW. Unusual cause of 'piriformis muscle syndrome'. Arch Neurol. 1990 Oct. 47(10):1144-6. [Medline].

  83. Patel RK, Cianca J, Nguyen D. Therapeutic efficacy of botulinum toxin A trigger point injections for patients with myofascial pain. American Academy of Physical Medicine and Rehabilitation 61st Annual Assembly and Technical Exhibition. 1999.

  84. Paulson GW, Gill W. Botulinum toxin is unsatisfactory therapy for fibromyalgia. Mov Disord. 1996 Jul. 11(4):459. [Medline].

  85. Porta M. A comparative trial of botulinum toxin type A and methylprednisolone for the treatment of myofascial pain syndrome and pain from chronic muscle spasm. Pain. 2000 Mar. 85(1-2):101-5. [Medline].

  86. Porta M, Loiero M, Gamba M, et al. Botulinum toxin type A versus steroid for the treatment of myofascial pain syndromes. International Conference 1999: Basic and Therapeutic Aspects of Botulinum and Tetanus Toxins. 1999. 73:

  87. Porta M, Maggioni G. Botulinum toxin (BoNT) and back pain. J Neurol. 2004 Feb. 251 Suppl 1:I15-8. [Medline].

  88. Qerama E, Fuglsang-Frederiksen A, Kasch H, et al. A double-blind, controlled study of botulinum toxin A in chronic myofascial pain. Neurology. 2006 Jul 25. 67(2):241-5. [Medline].

  89. Raj PP. Botulinum toxin therapy in pain management. Anesthesiol Clin North America. 2003 Dec. 21(4):715-31. [Medline].

  90. Reilich P, Fheodoroff K, Kern U, et al. Consensus statement: botulinum toxin in myofascial [corrected] pain. J Neurol. 2004 Feb. 251 Suppl 1:I36-8.

  91. Relja M, Telarovic S. Botulinum toxin in tension-type headache. J Neurol. 2004 Feb. 251 Suppl 1:I12-4. [Medline].

  92. Relja MA. Botulinum toxin type A in the treatment of tension-type headache. International Conference 1999: Basic and Therapeutic Aspects of Botulinum and Tetanus Toxins. 1999. 67:

  93. Rollnik JD, Dengler R. Botulinum toxin (DYSPORT) in tension-type headaches. Acta Neurochir Suppl. 2002. 79:123-6. [Medline].

  94. Rollnik JD, Tanneberger O, Schubert M. Treatment of tension-type headache with botulinum toxin type A: a double-blind, placebo-controlled study. Headache. 2000 Apr. 40(4):300-5. [Medline].

  95. Ron Y, Avni Y, Lukovetski A, et al. Botulinum toxin type-A in therapy of patients with anismus. Dis Colon Rectum. 2001 Dec. 44(12):1821-6. [Medline].

  96. Rosales RL, Arimura K, Takenaga S, et al. Extrafusal and intrafusal muscle effects in experimental botulinum toxin-A injection. Muscle Nerve. 1996 Apr. 19(4):488-96. [Medline].

  97. Schmitt WJ, Slowey E, Fravi N, et al. Effect of botulinum toxin A injections in the treatment of chronic tension-type headache: a double-blind, placebo-controlled trial. Headache. 2001 Jul-Aug. 41(7):658-64. [Medline].

  98. Schulte-Mattler WJ, Krack P. Treatment of chronic tension-type headache with botulinum toxin A: a randomized, double-blind, placebo-controlled multicenter study. Pain. 2004 May. 109(1-2):110-4. [Medline].

  99. Schulte-Mattler WJ, Opatz O, Blersch W, et al. Botulinum toxin A does not alter capsaicin-induced pain perception in human skin. J Neurol Sci. 2007 May 2. [Medline].

  100. Schulte-Mattler WJ, Wieser T, Aierz S. Treatment of tension-type headache with botulinum toxin: a pilot study. International conference 1999: basic and therapeutic aspects of botulinum and tetanus toxins. Vol 68. 1999.

  101. Schulte-Mattler WJ, Wieser T, Zierz S. Treatment of tension-type headache with botulinum toxin: a pilot study. Eur J Med Res. 1999 May 26. 4(5):183-6. [Medline].

  102. Shaari CM, Sanders I. Quantifying how location and dose of botulinum toxin injections affect muscle paralysis. Muscle Nerve. 1993 Sep. 16(9):964-9. [Medline].

  103. Sheean G. Botulinum toxin for the treatment of musculoskeletal pain and spasm. Curr Pain Headache Rep. 2002 Dec. 6(6):460-9. [Medline].

  104. Sheean GL, Murray NM, Marsden CD. Pain and remote weakness in limbs injected with botulinum toxin A for writer's cramp. Lancet. 1995 Jul 15. 346(8968):154-6. [Medline].

  105. Sherman S, Kopecky KK, Brashear A, et al. Percutaneous celiac plexus block with botulinum toxin A did not help the pain of chronic pancreatitis. J Clin Gastroenterol. 1995 Jun. 20(4):343-4. [Medline].

  106. Silberstein S, Mathew N, Saper J, et al. Botulinum toxin type A as a migraine preventive treatment. For the BOTOX Migraine Clinical Research Group. Headache. 2000 Jun. 40(6):445-50. [Medline].

  107. Simons DG, Travell JG. Myofascial origins of low back pain. 3. Pelvic and lower extremity muscles. Postgrad Med. 1983 Feb. 73(2):99-105, 108. [Medline].

  108. Simons DG, Travell JG, Simons LS. Travell & Simons' Myofascial pain and Dysfunction: The Trigger Point Manual. Baltimore, Md: Lippincott, Williams & Wilkins; 1999. 33.

  109. Smith HS, Audette J, Royal MA. Botulinum toxin in pain management of soft tissue syndromes. Clin J Pain. 2002 Nov-Dec. 18(6 Suppl):S147-54. [Medline].

  110. Smuts JA, Schultz D, Barnard A. Mechanism of action of botulinum toxin type A in migraine prevention: a pilot study. Headache. 2004 Sep. 44(8):801-5. [Medline].

  111. Smuts JA, Smuts HM, Baker MK, et al. Botulinum toxin type A as prophylactic treatment in chronic tension-type headache. International Conference 1999: Basic and Therapeutic Aspects of Botulinum and Tetanus Toxins. 1999. 68:

  112. Snyder-Mackler L, Bork C, Bourbon B, et al. Effect of helium-neon laser on musculoskeletal trigger points. Phys Ther. 1986 Jul. 66(7):1087-90. [Medline].

  113. Solheim LF, Siewers P, Paus B. The piriformis muscle syndrome. Sciatic nerve entrapment treated with section of the piriformis muscle. Acta Orthop Scand. 1981 Feb. 52(1):73-5.

  114. Steiner C, Staubs C, Ganon M, et al. Piriformis syndrome: pathogenesis, diagnosis, and treatment. J Am Osteopath Assoc. 1987 Apr. 87(4):318-23. [Medline].

  115. Sycha T, Kranz G, Auff E, et al. Botulinum toxin in the treatment of rare head and neck pain syndromes: a systematic review of the literature. J Neurol. 2004 Feb. 251 Suppl 1:I19-30.

  116. Thorsen H, Gam AN, Svensson BH, et al. Low level laser therapy for myofascial pain in the neck and shoulder girdle. A double-blind, cross-over study. Scand J Rheumatol. 1992. 21(3):139-41. [Medline].

  117. Van Daele DJ, Finnegan EM, Rodnitzky RL, et al. Head and neck muscle spasm after radiotherapy: management with botulinum toxin A injection. Arch Otolaryngol Head Neck Surg. 2002 Aug. 128(8):956-9.

  118. Vernick SH. Comments on Cheshire et al. (PAIN, 59 (1994) 65-69). Pain. 1995 Aug. 62(2):249. [Medline].

  119. Voller B, Sycha T, Gustorff B, et al. A randomized, double-blind, placebo controlled study on analgesic effects of botulinum toxin A. Neurology. 2003 Oct 14. 61(7):940-4. [Medline].

  120. Wheeler AH, Goolkasian P, Gretz SS. Botulinum toxin A for the treatment of chronic neck pain. Pain. 2001 Dec. 94(3):255-60. [Medline].

  121. Winner P, Cady R, Chun EM, et al. A multi-center double-blind, placebo-controlled trial of two dosages of botulinum toxin type A in the prophylactic treatment of migraine. International Conference 1999: Basic and Therapeutic Aspects of Botulinum and Tetanus Toxins. 1999. 68:

  122. Zermann D, Ishigooka M, Schubert J, et al. Perisphincteric injection of botulinum toxin type A. A treatment option for patients with chronic prostatic pain?. Eur Urol. 2000 Oct. 38(4):393-9. [Medline].

The Beatty maneuver.
Left piriformis muscle, posterior view. Inject 100 U botulinum toxin type A (BOTOX®) diluted in 3 mL saline into the area marked with an 'X' when guided by fluoroscopy.
Medscape Consult
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.