I n j e c t i o n s f o r C h ro n i c Pa i n Virtaj Singh,
MD
a,
*, Andrea Trescot,
MD
b
, Isuta Nishio,
MD
c
KEYWORDS Chronic pain Regenerative injections Trigger point injections Botulinum toxins KEY POINTS Even in the setting of chronic pain, various injections can still have a useful role in facilitating a rehabilitation program. Spinal injections, such as epidural steroid injections and facet joint injections, are among the most commonly used procedures in most pain practices; but a growing number of practices are considering less common injections, such as trigger point injections, regenerative injections/prolotherapy, and injections using botulinum toxins.
INTRODUCTION
Although interventional procedures should be used cautiously in the setting of chronic pain, there is a role for a variety of injections to facilitate patients’ overall rehabilitation program. There are many resources available, including a prior edition of Physical Medicine and Rehabilitation Clinics of North America, which discuss the more conventional spinal injections. The focus of this article is on lesser-known injection options for treating chronic pain. The authors separately discuss trigger point injections (TPIs), regenerative injections (prolotherapy), and injections using botulinum toxins (BTx). TRIGGER POINT INJECTIONS
Myofascial pain syndrome (MPS) is a common musculoskeletal pain syndrome characterized by a myofascial trigger point (MTrP) at muscle, fascia, or tendinous insertions. A MTrP is a hyperirritable tender spot, frequently associated with taut band that, on palpation, is firmer in consistency than adjacent muscle fibers. When compressed, an MTrP may cause patient vocalization or a visible withdrawal (which is known as the jump sign).
a Department of Rehabilitation Medicine, Seattle Spine & Sports Medicine, University of Washington, 3213 Eastlake Avenue East, Suite A, Seattle, WA 98102, USA; b Pain and Headache Center, 5431 Mayflower Lane, Suite 4, Wasilla, AK 99654, USA; c Department of Anesthesiology and Pain Medicine, VA Puget Sound Health Care System, University of Washington, 1660 South Columbian Way, S-112-Anes, Seattle, WA 98108, USA * Corresponding author. E-mail address: [email protected]
Phys Med Rehabil Clin N Am 26 (2015) 249–261 http://dx.doi.org/10.1016/j.pmr.2015.01.004 1047-9651/15/$ – see front matter Ó 2015 Elsevier Inc. All rights reserved.
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Stretching and exercise are the foundation of treatment and management of MPS; however, for refractory cases, needle therapy may be offered. This therapy may include TPIs (using local anesthetics, corticosteroids, and/or BTx), dry needling (DN) (intramuscular stimulation [IMS]), and acupuncture. Local Anesthetics
Despite the popularity of TPIs, there is no conclusive evidence that demonstrates superior effectiveness of TPIs over DN in the treatment of MPS.1,2 One systematic review of randomized controlled trials found that direct injection to MTrPs was indeed effective but that the nature of the injected substance did not influence the outcome; hence, the investigators concluded that the beneficial effects of TPIs were likely the result of needle insertion or placebo.1 However, another review showed short-term benefits of TPIs with lidocaine that were superior to DN or placebo.3 It is conceivable that local pain and soreness associated with needling can be ameliorated with local anesthetic injection.2 Corticosteroids
Although inflammation may play a role in MPS, there is no evidence that the injection of corticosteroid provides any enhanced benefits.4 In addition, corticosteroids carry the risk of local muscle necrosis and adrenal suppression. Thus, the use of corticosteroids for TPIs is not recommended. Botulinum Toxin
Botulinum toxin (BTx) is a potent neurotoxin produced by the bacterium Clostridium botulinum that blocks acetylcholine release into the neuromuscular junction, leading to prolonged muscle relaxation (typically lasting 3 to 4 months). BTx is used for a variety of pain procedures as discussed separately in this article later. Briefly, the authors discuss the use of BTx in TPIs. In TPIs, BTx is thought to reduce muscular ischemia and free entrapped nerve endings. Central and peripheral antinociceptive properties of BTx have also been postulated. Despite these mechanisms that could theoretically offer a benefit for patients with MPS, the use of BTx injections for myofascial trigger points is controversial. Meta-analyses of randomized trials in patients with neck pain have found no benefit of BTx intramuscular injections in the short-term (4 weeks) or long-term (6 months) when compared with placebo.5,6 Although a recent review7 showed inconclusive evidence regarding the effectiveness of BTx in the treatment of MPS, an older Cochrane review found moderate evidence that BTx injections are not effective.3 In sum, given the high cost of the medication and questionable evidence for its efficacy, cost and clinical value should be carefully assessed before considering BTx injections for MPS. Dry Needling
Dry needling (DN) (also known as intramuscular stimulation [IMS]) involves the practice of using a small-gauge needle (sometimes acupuncture needles) to irritate the MTrP without injecting any substance (as opposed to those discussed earlier). Systemic reviews and meta-analyses of randomized controlled trials suggest that DN is an effective therapy for MPS.1,8,9 If DN is used to specifically target MTrPs, it is most effective when a local twitch response (LTR) (brisk contraction of the taut band) is elicited.10 A fast-in-fast-out technique has been advocated to elicit a maximal number of LTRs. The needle penetrates the taut band of the muscle, is withdrawn to superficial subcutaneous tissue, then redirected to another area in proximity (Fig. 1). Deep DN to the
Injections for Chronic Pain
Taut band
Trigger point locus
Trigger point region
Fig. 1. TPIs and DN to myofascial trigger point. (Courtesy of Isuta Nishio, MD.)
muscle (eg, 15 mm) has been shown to be more effective than superficial DN (eg, 2 mm).11 Acupuncture
Acupuncture is an increasingly popular treatment of a broad spectrum of chronic conditions, including chronic pain. However, the number of needles used, the frequency of sessions, stimulation frequency, and current amplitude to obtain optimal efficacy remains a matter of debate. A Cochrane review found that, in the short-term, acupuncture is more effective for chronic low back pain and neck pain compared to no treatment or sham acupuncture.12 Other meta-analyses have also demonstrated the effectiveness of acupuncture for chronic pain when compared with no acupuncture or sham (needles placed in non-acupucture sites).13,14 The data suggest that the benefits of acupuncture are clinically relevant and greater than placebo; however, the observed differences in effectiveness between acupuncture and sham acupuncture are smaller than those between acupuncture and no acupuncture. This pattern of findings indicates that the nonspecific physiologic and psychological effects of needling may be more important than the actual acupuncture technique itself.14,15 Needing Therapy: Mechanism of Action
The exact mechanism by which DN relieves MTrP and MPS has yet to be fully elucidated. DN has been shown to diminish spontaneous electrical activity when LTR is elicited.16 Hong and Simons17 suggested that LTR or referred pain seems to be mediated through a spinal reflex in response to stimulation of a sensitive locus (nociceptor) that is in the vicinity of an active locus (motor end plate). Because DN is most effective when LTR is elicited,4 it is theorized that DN may relieve MTrP via inhibition of dysfunctional activity in the motor end plate of the skeletal muscle motor neuron. Acupuncture has been used for various pain conditions in addition to MPS. There is increasing evidence of correlations and similarities between MTrPs and acupuncture points in terms of their distribution and referred pain patterns.18,19 An electrophysiologic study showed that some acupuncture points are indeed MTrPs.20 Acupuncture analgesia seems to be a manifestation of integrative processes at different levels of the central nervous system (CNS).21 The gate control theory (Melzack and Wall22) may in part explain these processes; namely, the theory postulates that nonnoxious sensory input (eg, touch, pressure, vibration) into the CNS can modulate
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pain perception by activating inhibitory interneurons.22 Furthermore, the possible role of endogenous opioids has been implicated in both TPIs and acupuncture as their analgesic effects can be in part reversed by naloxone.23,24 Key Points
There is no firm evidence that TPIs are superior to DN or acupuncture for MPS; however, TPIs with local anesthetic may offer additional benefits via relieving pain associated with soreness from the needling procedure itself. There is no strong evidence to support the use of corticosteroid or BTx in TPIs. DN seems to be effective for MPS, especially when LTR is elicited. Acupuncture seems to be effective for chronic pain, but nonspecific physiologic and psychological effects may play a significant role in its benefits. The mechanism of action in needling therapy seems to be multifactorial, including integrative CNS processes and endogenous opioid peptides. REGENERATIVE INJECTIONS
Regenerative injection therapy (RIT) encompasses a spectrum of injection treatments designed to stimulate repair of damaged tissue. These injections range from prolotherapy (which provides a mild neurolytic effect followed by a complex restorative process with biochemically induced collagen regeneration), to platelet-rich plasma ([PRP], which uses autologous blood that has been spun down to separate out the platelets), to even stem cells (which can be autologous or banked). In 1956, George Hackett25 introduced the term fibroproliferative therapy or prolotherapy, defined as “the rehabilitation of an incompetent structure by generation of new cellular tissue.”25 He proposed this new name because the term sclerotherapy that had been used previously implied scar formation rather than regeneration. In the same text, he published composite pain maps generated from ligaments and tendons, which have unfortunately remained largely unknown to the medical community (Fig. 2). Contemporary understanding of the basic science of regenerative medicine is that the regenerative/reparative healing process consists of 3 overlapping phases: inflammatory, proliferative with granulation, and remodeling with contraction (Fig. 3). The regenerative and reparative stages extend beyond the proliferative stage. The term RIT was originally coined by Felix Linetskey, MD to replace the name prolotherapy; but authors have used both terms to describe any of the treatments described next. The first of these techniques, RIT/prolotherapy stimulates chemo-modulation of collagen by repetitive induction of inflammatory and proliferative stages, which leads to tissue regeneration and repair. As a result, the tensile strength, elasticity, mass, and load-bearing capacity of collagenous connective tissues increases. The proliferant, which can be any of a number solutions (including dextrose/lidocaine, dextrose/ phenol/glycerin, sodium morrhuate, and pumice), creates an inflammatory reaction, thereby generating new tissue at the fibro-osseous junction. Hormones and multiple growth factors mediate this complex process. Fig. 4 shows rabbit tendon hypertrophy after prolotherapy.26 The next technique, RIT/PRP relies on the injection of concentrated platelets that release growth factors to stimulate recovery in nonhealing soft tissues. Autologous blood is collected and centrifuged; the portion that contains a high proportion of platelets is syphoned off and injected into the tendon and ligament attachments at the enthesopathy site. RIT/stem cell injection involves utilization of autologous adult pluripotent mesenchymal stem cells from an individual’s bone marrow or adipose tissue as the
Injections for Chronic Pain
Fig. 2. Example of Hackett pain patterns. (Courtesy of Felix Linetsky, MD.)
proliferating solution. Alternatively, banked placental stem cells are beginning to come onto the market, facilitating stem cell procurement. Indications for RIT are listed in Box 1. Appropriate presenting complaints are diverse. These include occipital and suboccipital headaches; pain in the posterior midline and paramedial cervical spine, the cervicothoracic spine, the thoracic spine,
Fig. 3. Stages of wound healing. (Courtesy of Andrea Trescot, MD.)
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Fig. 4. Rabbit tendons after RIT (the left [L] is the untreated control and the right [R] is the treated side); (A) is after 6 weeks and (B) is after 3 months. (Courtesy of Felix Linetsky, MD.)
the thoracolumbar spine, the lumbar spine, the lumbosacral spine, the scapula, and the shoulder regions; pain between the shoulder blades, in the low back, buttocks, sacroiliac, trochanteric areas, and any combination of the aforementioned complaints. The onset of pain may be sudden or gradual; the intensity, duration, and quality of pain are variable but usually associated with a traumatic event. Physical examination may reveal postural abnormalities, functional asymmetries, as well as combinations of kyphoscoliosis, flattening of cervical and lumbar lordosis, or arm and/or leg length discrepancies. Variable combinations of flexion/extension, rotation, lateral bending, and/
Box 1 Indications for RIT 1. Painful enthesopathies, tendinosis, or ligamentosis from overuse and occupational and postural conditions known as repetitive motion disorders 2. Painful enthesopathies, tendinosis, or ligamentosis secondary to sprains or strains 3. Painful hypermobility, instability, and subluxation of the axial joints secondary to ligament laxity accompanied by restricted range of motion at reciprocal segments that improve temporarily with manipulation 4. Vertebral compression fractures with a wedge deformity that exert additional stress on the posterior ligamento-tendinous complex 5. Recurrent painful rib subluxations sternochondral articulations
at
the costotransverse,
costovertebral, and
6. Osteoarthritis, spondylosis, and spondylolisthesis 7. Postsurgical cervical, thoracic, and low back pain (with or without instrumentation) 8. Posterior column sources of nociception refractory to steroid injections, nonsteroidal antiinflammatory therapy, and radiofrequency procedures 9. Enhancement of manipulative treatment and physiotherapy 10. Internal disk derangement
Injections for Chronic Pain
or contractions under load can provoke pain. By correcting the ligament laxity that creates the anterior pressure on the disk (causing the disk to bulge posteriorly) and the facet instability (which causes spondylosis and reflex muscle contracture, leading to nerve entrapment), the underlying process can be halted and potentially reversed. These regenerative injections can be, and have been used, to treat painful conditions from head to toe (Fig. 5).
Splenius capitis
Longissimus capitis
Levator scapulae Interspinales
Rhomboids Supraspinatus
Iliocostalis cervicis
Trapezius Splenius cervicis
Deltoid Infraspinatus Teres minor Triceps
Iliocostalis thoracis
Teres major
Spinalis Longissimus thoracis and lumborum
Serratus posterior inferior
Iliocostalis lumborum Gluteus medius
Quadratus lumborum
Internal oblique
Multifidus
External oblique Sacrospinalis Gluteus minimus Coccygeus Gluteus maximus origin from sactrotuberous ligament
Semimembranosus Biceps femoris
Quadratus femoris Iliopsoas
Semitendinosus Adductor minimus
Adductor magnus Biceps femoris insertion to sacrotuberous ligament
Fig. 5. RIT injection sites. (Courtesy of Felix Linetsky, MD.)
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The exquisite tenderness at the fibro-osseous junction (enthesis) is the pertinent subjective clinical finding. These areas of tenderness are identified and marked to become the site of infiltration with local anesthetic. The initial needle placement at the fibro-osseous junction usually reproduces the pain, which temporarily worsens during infiltration of the local anesthetic and typically subsides within a few seconds after infiltration. Determination of abolishment or persistence of tenderness, plus the local or referred pain (which objectifies the finding of tenderness), concludes the clinical examination and becomes the basis for clinical diagnosis and further RIT procedures. The proliferant (dextrose/lidocaine for prolotherapy, platelets for PRP, or stem cells) can be injected subsequently or (with the dextrose) at the same time. RIT has been the subject of multiple published articles, including systematic reviews, randomized trials, and numerous nonrandomized publications, which include prospective and retrospective clinical studies as well as case reports. In a systematic review of prolotherapy injections for chronic low back pain,27 the investigators included 4 randomized trials28 that were considered high quality, with a total of 344 patients. Two of the four studies showed significant differences between the treatment and control groups with regard to the proportion of individuals who reported more than 50% reduction in pain or disability; however, the results of these studies could not be pooled. In addition, in one study, co-interventions confounded independent evaluation of results. In the second study of the review, there was no significant difference in mean pain and disability scores between the groups. In the third study, there was little or no difference between the groups with regard to the number of individuals who reported more than 50% improvement in pain and disability. Reporting only mean pain and disability scores, the fourth study showed no difference between groups. The authors of this systematic review concluded that there was conflicting evidence regarding the efficacy of prolotherapy injections in reducing pain and disability in patients with chronic low back pain. They also concluded that, in the presence of co-interventions, prolotherapy injections were more effective than placebo injections, and were yet more effective when both injections and co-interventions were controlled concurrently. In addition, there is substantial evidence for the effectiveness of prolotherapy from nonrandomized prospective and retrospective studies as well as case reports.29–41 In sum, the extant literature, although it does not offer convincing evidence as to the overall efficacy of prolotherapy, does offer moderate evidence to show its effectiveness in select patients when used with appropriate technique and co-interventions. Contraindications to RIT include general contraindications that are applicable to all injection techniques; specific contraindications for RIT are listed in Box 2. Complications do occur with RIT (as with any injection treatment), but statistically they are rare. There were several serious injuries in the 1950s when untrained providers injected toxic agents into the spinal column.42–44 The most recent statistical data are from a survey of 450 physicians who perform RIT/prolotherapy.45 Of the estimated 450,000 patients treated (each with at least 3 visits and at least 10 sites of injection), there were 29 incidences of pneumothorax, 2 of which required chest tube placement (risk of pneumothorax 5 1 per 18,333 injections). There were also 24 non–life-threatening allergic reactions; postdural puncture headaches,46 end plate fractures (after intradiscal dextrose),47 sterile meningitis,48 and cervical spine injuries49 have also been described. Although risk is inherent in any active intervention, regeneration of worn, frayed, and lax ligaments and tendons holds the promise of treating the cause of the pain rather than just masking it or ablating the nerves that innervate it. Through the use of the body’s own healing power, RIT holds the promise of restoration of function and reduction in pain.
Injections for Chronic Pain
Box 2 Contraindications for RIT General contraindications Allergy to anesthetic solutions Bacterial infection, systemic or localized to the region to be injected Bleeding diathesis secondary to disease or anticoagulants Fear of the procedure or needle phobia Neoplastic lesions involving the musculature and osseous structures Recent onset of a progressive neurologic deficit Requests for large quantity of sedation and/or opioids before and after treatment Severe exacerbation of pain or lack of improvement after local anesthetic blocks Specific contraindications Acute arthritis (septic, gout, rheumatoid, or posttraumatic with hemarthrosis) Acute bursitis or tendonitis Acute nonreduced subluxations, dislocations, or fractures Allergy to injectable solutions or their ingredients, such as dextrose (corn), sodium morrhuate (fish), or phenol
Key Points
RIT encompasses a spectrum of injection treatments designed to stimulate repair of damaged tissue. Contemporary understanding of the basic science of regenerative medicine is that the regenerative/reparative healing process consists of 3 overlapping phases: inflammatory, proliferative with granulation, and remodeling with contraction. Appropriate presenting complaints are diverse and include occipital and suboccipital headaches; pain in the posterior midline and paramedial cervical spine, the cervicothoracic spine, the thoracic spine, the thoracolumbar spine, the lumbar spine, the lumbosacral spine, the scapula, and the shoulder regions; pain between the shoulder blades, pain in the low back, buttocks, sacroiliac, trochanteric areas; and any combination of the aforementioned complaints. The extant literature, although it does not offer convincing evidence as to the overall efficacy of prolotherapy, does offer moderate evidence to show its effectiveness in select patients when used with appropriate technique and co-interventions. BOTULINUM TOXIN (BTx) injection
Injectable BTx is frequently used in both physiatric and pain practices. In general physiatry, it is commonly used to treat spasticity, such as that found after a stroke or spinal cord injury. Within pain practices, it is used for a variety of pain syndromes and is often used off-label. The mechanism of action and other theoretic aspects of these toxins are discussed earlier in this article as is their use for TPIs (which is also considered off-label). BTx comes in a variety of formulations, including type A (Botox, Dysport, and Xeomin) and type B (Myobloc). Botox is Food and Drug Administration (FDA) approved for use in migraine headaches (as discussed elsewhere in this edition). For the remainder of the current article, the authors focus on the use of BTx for cervical dystonia, thoracic outlet syndrome, and piriformis syndrome.
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In addition to having received FDA approval for migraine headaches, some forms of BTx are FDA approved for use in cervical dystonia. Cervical dystonia, also known as spasmodic torticollis, is a cervical spine condition characterized by involuntary contractions of the neck and/or shoulder muscles resulting in abnormal head postures. Neck pain is often an associated symptom in cervical dystonia. BTx injections have been shown in multiple randomized controlled trials to effectively relieve the involuntary contractions, spasms, and pain associated with this condition.50 Thoracic outlet syndrome (which may actually be a variant of cervical dystonia) is another condition in which the use of BTx injections may be indicated. Thoracic outlet syndrome is a controversial diagnosis characterized by neurovascular compression within the thoracic outlet. This condition often results from a combination of hypertonic/dystonic muscles, especially the anterior and middle scalenes. Injecting BTx into these muscles has been shown to effectively relieve the symptoms of thoracic outlet syndrome.51 Although BTx is not FDA approved for the treatment of thoracic outlet syndrome, if the thoracic outlet syndrome is a secondary condition caused by cervical dystonia, then one could make a case for the use of BTx as an FDA approved indication in this scenario. Piriformis syndrome is another controversial diagnosis. It is characterized by sciatic nerve irritation/compression from presumed hypertonicity of the piriformis muscle. Typical patients describe a deep pain in the buttock and can have symptoms that mimic those associated with a classic L5 and/or S1 radiculopathy. Some clinicians refer to piriformis syndrome as pseudosciatica. In addition to piriformis syndrome being a controversial diagnosis, the treatment is similarly controversial, especially with the use of BTx. If priformis syndrome is indeed caused by piriformis hypertonicity, BTx would likely be effective in reducing the hypertonicity and taking pressure off the sciatic nerve. This use is currently off-label, but several studies do demonstrate the effectiveness of BTx for this condition.52,53 Key Points
BTx can be used for various pain diagnoses, including migraines, cervical dystonia, thoracic outlet syndrome, and piriformis syndrome. The use of BTx for pain procedures is often off-label, and its use is considered controversial. SUMMARY
Even in the setting of chronic pain, various injections can still have a useful role in facilitating a rehabilitation program. Spinal injections, such as epidural steroid injections and facet joint injections, are among the most commonly used procedures in pain practices; however a growing number of practices are considering less common injections, such as various TPIs, regenerative injections/prolotherapy, and injections using BTx. REFERENCES
1. Cumming TM, White AR. Needling therapies in the management of myofascial trigger point pain: a systematic review. Arch Phys Med Rehabil 2001;82:986–92. 2. Scott NA, Guo B, Barton PM, et al. Trigger point injections for chronic nonmalignant musculoskeletal pain: a systematic review. Pain Med 2009;10:54–69. 3. Peloso P, Gross A, Haines T, et al. Cervical overview group. Medicinal and injection therapies for mechanical neck disorders. Cochrane Database Syst Rev 2007;(3):CD000319.
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4. Staal JB, de Bie RA, de Vet HC, et al. Injection therapy for subacute and chronic low back pain: an updated Cochrane review. Spine 2009;34:49–59. 5. Langevin P, Lowcock J, Weber J, et al. Cervical overview group. Botulinum toxin intramuscular injections for neck pain: a systematic review and meta-analysis. J Rheumatol 2011;38:203–14. 6. Langevin P, Peloso PM, Lowcock J, et al. Botulinum toxin for subacute/chronic neck pain. Cochrane Database Syst Rev 2011;(7):CD008626. 7. Soares A, Andriolo RB, Atallah AN, et al. Botulinum toxin for myofascial pain syndromes in adults. Cochrane Database Syst Rev 2014;(7):CD007533. 8. Tough EA, White AR, Cummings TM, et al. Acupuncture and dry needling in the management of myofascial trigger point pain: a systematic review and metaanalysis of randomised controlled trials. Eur J Pain 2009;13:3–10. 9. Kietrys DM, Palombaro KM, Azzaretto E, et al. Effectiveness of dry needling for upper-quarter myofascial pain: a systematic review and meta-analysis. J Orthop Sports Phys Ther 2013;43:620–34. 10. Hong CZ. Lidocaine injection versus dry needling to myofascial trigger point. The importance of the local twitch response. Am J Phys Med Rehabil 1994;73:256–63. 11. Ceccherelli F, Rigoni MT, Gagliardi G, et al. Comparison of superficial and deep acupuncture in the treatment of lumbar myofascial pain: a double-blind randomized controlled study. Clin J Pain 2002;18:149–53. 12. Furlan AD, van Tulder M, Cherkin D, et al. Acupuncture and dry-needling for low back pain: an updated systematic review within the framework of the Cochrane collaboration. Spine 2005;30:944–63. 13. Lam M, Galvin R, Curry P. Effectiveness of acupuncture for nonspecific chronic low back pain: a systematic review and meta-analysis. Spine 2013;38:2124–38. 14. Vickers AJ, Cronin AM, Maschino AC, et al. Acupuncture trialists’ collaboration. Acupuncture for chronic pain: individual patient data meta-analysis. Arch Intern Med 2012;172:1444–53. 15. Vickers AJ, Linde K. Acupuncture for chronic pain. JAMA 2014;311:955–6. 16. Chen JT, Chung KC, Hou CR, et al. Inhibitory effect of dry needling on the spontaneous electrical activity recorded from myofascial trigger spots of rabbit skeletal muscle. Am J Phys Med Rehabil 2001;80:729–35. 17. Hong CZ, Simons DG. Pathophysiologic and electrophysiologic mechanisms of myofascial trigger points. Arch Phys Med Rehabil 1998;79:863–72. 18. Melzack R, Stillwell DM, Fox J. Trigger points and acupuncture points for chronic pain: correlations and implications. Pain 1977;3:3–23. 19. Dorsher PT. Myofascial referred-pain data provide physiologic evidence of acupuncture meridians. J Pain 2009;10:723–31. 20. Kao MJ, Hsieh YL, Kuo FJ, et al. Electrophysiological assessment of acupuncture points. Am J Phys Med Rehabil 2006;85:443–8. 21. Zhao ZQ. Neural mechanism underlying acupuncture analgesia. Prog Neurobiol 2008;85:355–75. 22. Melzack R, Wall PD. Pain mechanism: a new theory. Science 1965;150:971–9. 23. Fine PG, Milano R, Hare BD. The effects of myofascial trigger point injections are naloxone reversible. Pain 1988;32:15–20. 24. Wang SM, Kain ZN, White P. Acupuncture analgesia: I. The scientific basis. Anesth Analg 2008;106:602–10. 25. Hackett GS. Joint ligament relaxation treated by fibro-osseous proliferation. 1st edition. Springfield (IL): Charles C. Thomas; 1956. 26. Leadbetter WB. Cell-matrix response in tendon injury. Clin Sports Med 1992; 11(3):533–78.
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27. Yelland MJ, Del Mar C, Pirozzo S, et al. Prolotherapy injections for chronic low back pain: a systematic review. Spine 2004;29(19):2126–33. 28. Nelemans PJ, deBie RA, deVet HC, et al. Injection therapy for subacute and chronic benign low back pain. Spine (Phila Pa 1976) 2001;26(5):501–15. 29. Topol GA, Reeves KD, Hassanein KM. Efficacy of dextrose prolotherapy in elite male kicking-sport athletes with chronic groin pain. Arch Phys Med Rehabil 2005;86(4):697–702. 30. Scarpone M, Rabago DP, Zgierska A, et al. The efficacy of prolotherapy for lateral epicondylosis: a pilot study. Clin J Sport Med 2008;18(3):248–54. 31. Reeves KD, Hassanein KM. Long-term effects of dextrose prolotherapy for anterior cruciate ligament laxity. Altern Ther Health Med 2003;9(3):58–62. 32. Reeves KD, Hassanein K. Randomized prospective double-blind placebocontrolled study of dextrose prolotherapy for knee osteoarthritis with or without ACL laxity. Altern Ther Health Med 2000;6(2):68–74, 77–80. 33. Rabago D. Prolotherapy for treatment of lateral epicondylosis. Am Fam Physician 2009;80(5):441. 34. Merriman JR. Prolotherapy versus operative fusion in the treatment of joint instability of the spine and pelvis. J Int Coll Surg 1964;42:150–9. 35. Mathews R, Miller M, Bree S. Treatment of mechanical and chemical lumbar discopathy by dextrose 25%. J Minimally Invasive Spinal Technique 2001; 1(1):58–61. 36. Linetsky FS, Miguel R, Torres F. Treatment of cervicothoracic pain and cervicogenic headaches with regenerative injection therapy. Curr Pain Headache Rep 2004;8(1):41–8. 37. Klein RG, Eek BC, DeLong WB, et al. A randomized double-blind trial of dextroseglycerine-phenol injections for chronic, low back pain. J Spinal Disord 1993;6(1): 23–33. 38. Klein RG, Dorman TA, Johnson CE. Proliferant injections for low back pain: histologic changes of injected ligaments and objective measurements of lumbar spine mobility before and after treatment. J Neurol Orthop Med Surg 1989;10:123–6. 39. Fullerton BD, Reeves KD. Ultrasonography in regenerative injection (prolotherapy) using dextrose, platelet-rich plasma, and other injectants. Phys Med Rehabil Clin N Am 2010;21(3):585–605. 40. Centeno CJ, Elliott J, Elkins WL, et al. Fluoroscopically guided cervical prolotherapy for instability with blinded pre and post radiographic reading. Pain Physician 2005;8(1):67–72. 41. Carayannopoulos A, Borg-Stein J, Sokolof J, et al. Prolotherapy versus corticosteroid injections for the treatment of lateral epicondylosis: a randomized controlled trial. PMR 2011;3(8):706–15. 42. Schneider RC, Williams JJ, Liss L. Fatality after injection of sclerosing agent to precipitate fibro-osseous proliferation. J Am Med Assoc 1959;170(15):1768–72. 43. Keplinger JE, Bucy PC. Paraplegia from treatment with sclerosing agents. Report of a case. JAMA 1960;173:1333–5. 44. Hunt WE, Baird WC. Complications following injection of sclerosing agent to precipitate fibro-osseous proliferation. J Neurosurg 1961;18:461–5. 45. Dorman TA. Prolotherapy: a survey. J Orthop Med 1993;15:49–50. 46. Yelland MJ, Glasziou PP, Bogduk N, et al. Prolotherapy injections, saline injections, and exercises for chronic low-back pain: a randomized trial. Spine 2004; 29(1):9–16 [discussion: 16]. 47. Whitworth ML. Endplate fracture associated with intradiscal dextrose injection. Pain Physician 2002;5(4):379–84.
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48. Grayson M. Sterile meningitis after lumbosacral ligament sclerosing injections. J Orthop Med 1994;16(3):98–9. 49. Yun HS, Sun HS, Seon HJ, et al. Prolotherapy-induced cervical spinal cord injury -a case report. Ann Rehabil Med 2012;35(4):570–3. 50. Lew MF, Brashear A, Factor S. The safety and efficacy of botulin toxin type B in the treatment of patients with cervical dystonia. A summary of three controlled trials. Neurology 2000;55(12 suppl 5):529–35. 51. Jordan SE, Ahn SS, Freischlag JA, et al. Selective botulinum chemodenervation of the scalene muscles for treatment of neurogenic thoracic outlet syndrome. Ann Vasc Surg 2000;14(4):365–9. 52. Fishman L, Konnoth C, Rozner B. Botulinum neurotoxin type B and physical therapy in the treatment of piriformis syndrome: a dose-finding study. Am J Phys Med Rehabil 2004;83:42–50. 53. Lang AM. Botulin toxin type B in piriformis syndrome. AM J Phys Med Rehabil 2004;83(3):198–202.
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*, Andrea Trescot,
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, Isuta Nishio,
MD
c
KEYWORDS Chronic pain Regenerative injections Trigger point injections Botulinum toxins KEY POINTS Even in the setting of chronic pain, various injections can still have a useful role in facilitating a rehabilitation program. Spinal injections, such as epidural steroid injections and facet joint injections, are among the most commonly used procedures in most pain practices; but a growing number of practices are considering less common injections, such as trigger point injections, regenerative injections/prolotherapy, and injections using botulinum toxins.
INTRODUCTION
Although interventional procedures should be used cautiously in the setting of chronic pain, there is a role for a variety of injections to facilitate patients’ overall rehabilitation program. There are many resources available, including a prior edition of Physical Medicine and Rehabilitation Clinics of North America, which discuss the more conventional spinal injections. The focus of this article is on lesser-known injection options for treating chronic pain. The authors separately discuss trigger point injections (TPIs), regenerative injections (prolotherapy), and injections using botulinum toxins (BTx). TRIGGER POINT INJECTIONS
Myofascial pain syndrome (MPS) is a common musculoskeletal pain syndrome characterized by a myofascial trigger point (MTrP) at muscle, fascia, or tendinous insertions. A MTrP is a hyperirritable tender spot, frequently associated with taut band that, on palpation, is firmer in consistency than adjacent muscle fibers. When compressed, an MTrP may cause patient vocalization or a visible withdrawal (which is known as the jump sign).
a Department of Rehabilitation Medicine, Seattle Spine & Sports Medicine, University of Washington, 3213 Eastlake Avenue East, Suite A, Seattle, WA 98102, USA; b Pain and Headache Center, 5431 Mayflower Lane, Suite 4, Wasilla, AK 99654, USA; c Department of Anesthesiology and Pain Medicine, VA Puget Sound Health Care System, University of Washington, 1660 South Columbian Way, S-112-Anes, Seattle, WA 98108, USA * Corresponding author. E-mail address: [email protected]
Phys Med Rehabil Clin N Am 26 (2015) 249–261 http://dx.doi.org/10.1016/j.pmr.2015.01.004 1047-9651/15/$ – see front matter Ó 2015 Elsevier Inc. All rights reserved.
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Stretching and exercise are the foundation of treatment and management of MPS; however, for refractory cases, needle therapy may be offered. This therapy may include TPIs (using local anesthetics, corticosteroids, and/or BTx), dry needling (DN) (intramuscular stimulation [IMS]), and acupuncture. Local Anesthetics
Despite the popularity of TPIs, there is no conclusive evidence that demonstrates superior effectiveness of TPIs over DN in the treatment of MPS.1,2 One systematic review of randomized controlled trials found that direct injection to MTrPs was indeed effective but that the nature of the injected substance did not influence the outcome; hence, the investigators concluded that the beneficial effects of TPIs were likely the result of needle insertion or placebo.1 However, another review showed short-term benefits of TPIs with lidocaine that were superior to DN or placebo.3 It is conceivable that local pain and soreness associated with needling can be ameliorated with local anesthetic injection.2 Corticosteroids
Although inflammation may play a role in MPS, there is no evidence that the injection of corticosteroid provides any enhanced benefits.4 In addition, corticosteroids carry the risk of local muscle necrosis and adrenal suppression. Thus, the use of corticosteroids for TPIs is not recommended. Botulinum Toxin
Botulinum toxin (BTx) is a potent neurotoxin produced by the bacterium Clostridium botulinum that blocks acetylcholine release into the neuromuscular junction, leading to prolonged muscle relaxation (typically lasting 3 to 4 months). BTx is used for a variety of pain procedures as discussed separately in this article later. Briefly, the authors discuss the use of BTx in TPIs. In TPIs, BTx is thought to reduce muscular ischemia and free entrapped nerve endings. Central and peripheral antinociceptive properties of BTx have also been postulated. Despite these mechanisms that could theoretically offer a benefit for patients with MPS, the use of BTx injections for myofascial trigger points is controversial. Meta-analyses of randomized trials in patients with neck pain have found no benefit of BTx intramuscular injections in the short-term (4 weeks) or long-term (6 months) when compared with placebo.5,6 Although a recent review7 showed inconclusive evidence regarding the effectiveness of BTx in the treatment of MPS, an older Cochrane review found moderate evidence that BTx injections are not effective.3 In sum, given the high cost of the medication and questionable evidence for its efficacy, cost and clinical value should be carefully assessed before considering BTx injections for MPS. Dry Needling
Dry needling (DN) (also known as intramuscular stimulation [IMS]) involves the practice of using a small-gauge needle (sometimes acupuncture needles) to irritate the MTrP without injecting any substance (as opposed to those discussed earlier). Systemic reviews and meta-analyses of randomized controlled trials suggest that DN is an effective therapy for MPS.1,8,9 If DN is used to specifically target MTrPs, it is most effective when a local twitch response (LTR) (brisk contraction of the taut band) is elicited.10 A fast-in-fast-out technique has been advocated to elicit a maximal number of LTRs. The needle penetrates the taut band of the muscle, is withdrawn to superficial subcutaneous tissue, then redirected to another area in proximity (Fig. 1). Deep DN to the
Injections for Chronic Pain
Taut band
Trigger point locus
Trigger point region
Fig. 1. TPIs and DN to myofascial trigger point. (Courtesy of Isuta Nishio, MD.)
muscle (eg, 15 mm) has been shown to be more effective than superficial DN (eg, 2 mm).11 Acupuncture
Acupuncture is an increasingly popular treatment of a broad spectrum of chronic conditions, including chronic pain. However, the number of needles used, the frequency of sessions, stimulation frequency, and current amplitude to obtain optimal efficacy remains a matter of debate. A Cochrane review found that, in the short-term, acupuncture is more effective for chronic low back pain and neck pain compared to no treatment or sham acupuncture.12 Other meta-analyses have also demonstrated the effectiveness of acupuncture for chronic pain when compared with no acupuncture or sham (needles placed in non-acupucture sites).13,14 The data suggest that the benefits of acupuncture are clinically relevant and greater than placebo; however, the observed differences in effectiveness between acupuncture and sham acupuncture are smaller than those between acupuncture and no acupuncture. This pattern of findings indicates that the nonspecific physiologic and psychological effects of needling may be more important than the actual acupuncture technique itself.14,15 Needing Therapy: Mechanism of Action
The exact mechanism by which DN relieves MTrP and MPS has yet to be fully elucidated. DN has been shown to diminish spontaneous electrical activity when LTR is elicited.16 Hong and Simons17 suggested that LTR or referred pain seems to be mediated through a spinal reflex in response to stimulation of a sensitive locus (nociceptor) that is in the vicinity of an active locus (motor end plate). Because DN is most effective when LTR is elicited,4 it is theorized that DN may relieve MTrP via inhibition of dysfunctional activity in the motor end plate of the skeletal muscle motor neuron. Acupuncture has been used for various pain conditions in addition to MPS. There is increasing evidence of correlations and similarities between MTrPs and acupuncture points in terms of their distribution and referred pain patterns.18,19 An electrophysiologic study showed that some acupuncture points are indeed MTrPs.20 Acupuncture analgesia seems to be a manifestation of integrative processes at different levels of the central nervous system (CNS).21 The gate control theory (Melzack and Wall22) may in part explain these processes; namely, the theory postulates that nonnoxious sensory input (eg, touch, pressure, vibration) into the CNS can modulate
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pain perception by activating inhibitory interneurons.22 Furthermore, the possible role of endogenous opioids has been implicated in both TPIs and acupuncture as their analgesic effects can be in part reversed by naloxone.23,24 Key Points
There is no firm evidence that TPIs are superior to DN or acupuncture for MPS; however, TPIs with local anesthetic may offer additional benefits via relieving pain associated with soreness from the needling procedure itself. There is no strong evidence to support the use of corticosteroid or BTx in TPIs. DN seems to be effective for MPS, especially when LTR is elicited. Acupuncture seems to be effective for chronic pain, but nonspecific physiologic and psychological effects may play a significant role in its benefits. The mechanism of action in needling therapy seems to be multifactorial, including integrative CNS processes and endogenous opioid peptides. REGENERATIVE INJECTIONS
Regenerative injection therapy (RIT) encompasses a spectrum of injection treatments designed to stimulate repair of damaged tissue. These injections range from prolotherapy (which provides a mild neurolytic effect followed by a complex restorative process with biochemically induced collagen regeneration), to platelet-rich plasma ([PRP], which uses autologous blood that has been spun down to separate out the platelets), to even stem cells (which can be autologous or banked). In 1956, George Hackett25 introduced the term fibroproliferative therapy or prolotherapy, defined as “the rehabilitation of an incompetent structure by generation of new cellular tissue.”25 He proposed this new name because the term sclerotherapy that had been used previously implied scar formation rather than regeneration. In the same text, he published composite pain maps generated from ligaments and tendons, which have unfortunately remained largely unknown to the medical community (Fig. 2). Contemporary understanding of the basic science of regenerative medicine is that the regenerative/reparative healing process consists of 3 overlapping phases: inflammatory, proliferative with granulation, and remodeling with contraction (Fig. 3). The regenerative and reparative stages extend beyond the proliferative stage. The term RIT was originally coined by Felix Linetskey, MD to replace the name prolotherapy; but authors have used both terms to describe any of the treatments described next. The first of these techniques, RIT/prolotherapy stimulates chemo-modulation of collagen by repetitive induction of inflammatory and proliferative stages, which leads to tissue regeneration and repair. As a result, the tensile strength, elasticity, mass, and load-bearing capacity of collagenous connective tissues increases. The proliferant, which can be any of a number solutions (including dextrose/lidocaine, dextrose/ phenol/glycerin, sodium morrhuate, and pumice), creates an inflammatory reaction, thereby generating new tissue at the fibro-osseous junction. Hormones and multiple growth factors mediate this complex process. Fig. 4 shows rabbit tendon hypertrophy after prolotherapy.26 The next technique, RIT/PRP relies on the injection of concentrated platelets that release growth factors to stimulate recovery in nonhealing soft tissues. Autologous blood is collected and centrifuged; the portion that contains a high proportion of platelets is syphoned off and injected into the tendon and ligament attachments at the enthesopathy site. RIT/stem cell injection involves utilization of autologous adult pluripotent mesenchymal stem cells from an individual’s bone marrow or adipose tissue as the
Injections for Chronic Pain
Fig. 2. Example of Hackett pain patterns. (Courtesy of Felix Linetsky, MD.)
proliferating solution. Alternatively, banked placental stem cells are beginning to come onto the market, facilitating stem cell procurement. Indications for RIT are listed in Box 1. Appropriate presenting complaints are diverse. These include occipital and suboccipital headaches; pain in the posterior midline and paramedial cervical spine, the cervicothoracic spine, the thoracic spine,
Fig. 3. Stages of wound healing. (Courtesy of Andrea Trescot, MD.)
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Fig. 4. Rabbit tendons after RIT (the left [L] is the untreated control and the right [R] is the treated side); (A) is after 6 weeks and (B) is after 3 months. (Courtesy of Felix Linetsky, MD.)
the thoracolumbar spine, the lumbar spine, the lumbosacral spine, the scapula, and the shoulder regions; pain between the shoulder blades, in the low back, buttocks, sacroiliac, trochanteric areas, and any combination of the aforementioned complaints. The onset of pain may be sudden or gradual; the intensity, duration, and quality of pain are variable but usually associated with a traumatic event. Physical examination may reveal postural abnormalities, functional asymmetries, as well as combinations of kyphoscoliosis, flattening of cervical and lumbar lordosis, or arm and/or leg length discrepancies. Variable combinations of flexion/extension, rotation, lateral bending, and/
Box 1 Indications for RIT 1. Painful enthesopathies, tendinosis, or ligamentosis from overuse and occupational and postural conditions known as repetitive motion disorders 2. Painful enthesopathies, tendinosis, or ligamentosis secondary to sprains or strains 3. Painful hypermobility, instability, and subluxation of the axial joints secondary to ligament laxity accompanied by restricted range of motion at reciprocal segments that improve temporarily with manipulation 4. Vertebral compression fractures with a wedge deformity that exert additional stress on the posterior ligamento-tendinous complex 5. Recurrent painful rib subluxations sternochondral articulations
at
the costotransverse,
costovertebral, and
6. Osteoarthritis, spondylosis, and spondylolisthesis 7. Postsurgical cervical, thoracic, and low back pain (with or without instrumentation) 8. Posterior column sources of nociception refractory to steroid injections, nonsteroidal antiinflammatory therapy, and radiofrequency procedures 9. Enhancement of manipulative treatment and physiotherapy 10. Internal disk derangement
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or contractions under load can provoke pain. By correcting the ligament laxity that creates the anterior pressure on the disk (causing the disk to bulge posteriorly) and the facet instability (which causes spondylosis and reflex muscle contracture, leading to nerve entrapment), the underlying process can be halted and potentially reversed. These regenerative injections can be, and have been used, to treat painful conditions from head to toe (Fig. 5).
Splenius capitis
Longissimus capitis
Levator scapulae Interspinales
Rhomboids Supraspinatus
Iliocostalis cervicis
Trapezius Splenius cervicis
Deltoid Infraspinatus Teres minor Triceps
Iliocostalis thoracis
Teres major
Spinalis Longissimus thoracis and lumborum
Serratus posterior inferior
Iliocostalis lumborum Gluteus medius
Quadratus lumborum
Internal oblique
Multifidus
External oblique Sacrospinalis Gluteus minimus Coccygeus Gluteus maximus origin from sactrotuberous ligament
Semimembranosus Biceps femoris
Quadratus femoris Iliopsoas
Semitendinosus Adductor minimus
Adductor magnus Biceps femoris insertion to sacrotuberous ligament
Fig. 5. RIT injection sites. (Courtesy of Felix Linetsky, MD.)
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The exquisite tenderness at the fibro-osseous junction (enthesis) is the pertinent subjective clinical finding. These areas of tenderness are identified and marked to become the site of infiltration with local anesthetic. The initial needle placement at the fibro-osseous junction usually reproduces the pain, which temporarily worsens during infiltration of the local anesthetic and typically subsides within a few seconds after infiltration. Determination of abolishment or persistence of tenderness, plus the local or referred pain (which objectifies the finding of tenderness), concludes the clinical examination and becomes the basis for clinical diagnosis and further RIT procedures. The proliferant (dextrose/lidocaine for prolotherapy, platelets for PRP, or stem cells) can be injected subsequently or (with the dextrose) at the same time. RIT has been the subject of multiple published articles, including systematic reviews, randomized trials, and numerous nonrandomized publications, which include prospective and retrospective clinical studies as well as case reports. In a systematic review of prolotherapy injections for chronic low back pain,27 the investigators included 4 randomized trials28 that were considered high quality, with a total of 344 patients. Two of the four studies showed significant differences between the treatment and control groups with regard to the proportion of individuals who reported more than 50% reduction in pain or disability; however, the results of these studies could not be pooled. In addition, in one study, co-interventions confounded independent evaluation of results. In the second study of the review, there was no significant difference in mean pain and disability scores between the groups. In the third study, there was little or no difference between the groups with regard to the number of individuals who reported more than 50% improvement in pain and disability. Reporting only mean pain and disability scores, the fourth study showed no difference between groups. The authors of this systematic review concluded that there was conflicting evidence regarding the efficacy of prolotherapy injections in reducing pain and disability in patients with chronic low back pain. They also concluded that, in the presence of co-interventions, prolotherapy injections were more effective than placebo injections, and were yet more effective when both injections and co-interventions were controlled concurrently. In addition, there is substantial evidence for the effectiveness of prolotherapy from nonrandomized prospective and retrospective studies as well as case reports.29–41 In sum, the extant literature, although it does not offer convincing evidence as to the overall efficacy of prolotherapy, does offer moderate evidence to show its effectiveness in select patients when used with appropriate technique and co-interventions. Contraindications to RIT include general contraindications that are applicable to all injection techniques; specific contraindications for RIT are listed in Box 2. Complications do occur with RIT (as with any injection treatment), but statistically they are rare. There were several serious injuries in the 1950s when untrained providers injected toxic agents into the spinal column.42–44 The most recent statistical data are from a survey of 450 physicians who perform RIT/prolotherapy.45 Of the estimated 450,000 patients treated (each with at least 3 visits and at least 10 sites of injection), there were 29 incidences of pneumothorax, 2 of which required chest tube placement (risk of pneumothorax 5 1 per 18,333 injections). There were also 24 non–life-threatening allergic reactions; postdural puncture headaches,46 end plate fractures (after intradiscal dextrose),47 sterile meningitis,48 and cervical spine injuries49 have also been described. Although risk is inherent in any active intervention, regeneration of worn, frayed, and lax ligaments and tendons holds the promise of treating the cause of the pain rather than just masking it or ablating the nerves that innervate it. Through the use of the body’s own healing power, RIT holds the promise of restoration of function and reduction in pain.
Injections for Chronic Pain
Box 2 Contraindications for RIT General contraindications Allergy to anesthetic solutions Bacterial infection, systemic or localized to the region to be injected Bleeding diathesis secondary to disease or anticoagulants Fear of the procedure or needle phobia Neoplastic lesions involving the musculature and osseous structures Recent onset of a progressive neurologic deficit Requests for large quantity of sedation and/or opioids before and after treatment Severe exacerbation of pain or lack of improvement after local anesthetic blocks Specific contraindications Acute arthritis (septic, gout, rheumatoid, or posttraumatic with hemarthrosis) Acute bursitis or tendonitis Acute nonreduced subluxations, dislocations, or fractures Allergy to injectable solutions or their ingredients, such as dextrose (corn), sodium morrhuate (fish), or phenol
Key Points
RIT encompasses a spectrum of injection treatments designed to stimulate repair of damaged tissue. Contemporary understanding of the basic science of regenerative medicine is that the regenerative/reparative healing process consists of 3 overlapping phases: inflammatory, proliferative with granulation, and remodeling with contraction. Appropriate presenting complaints are diverse and include occipital and suboccipital headaches; pain in the posterior midline and paramedial cervical spine, the cervicothoracic spine, the thoracic spine, the thoracolumbar spine, the lumbar spine, the lumbosacral spine, the scapula, and the shoulder regions; pain between the shoulder blades, pain in the low back, buttocks, sacroiliac, trochanteric areas; and any combination of the aforementioned complaints. The extant literature, although it does not offer convincing evidence as to the overall efficacy of prolotherapy, does offer moderate evidence to show its effectiveness in select patients when used with appropriate technique and co-interventions. BOTULINUM TOXIN (BTx) injection
Injectable BTx is frequently used in both physiatric and pain practices. In general physiatry, it is commonly used to treat spasticity, such as that found after a stroke or spinal cord injury. Within pain practices, it is used for a variety of pain syndromes and is often used off-label. The mechanism of action and other theoretic aspects of these toxins are discussed earlier in this article as is their use for TPIs (which is also considered off-label). BTx comes in a variety of formulations, including type A (Botox, Dysport, and Xeomin) and type B (Myobloc). Botox is Food and Drug Administration (FDA) approved for use in migraine headaches (as discussed elsewhere in this edition). For the remainder of the current article, the authors focus on the use of BTx for cervical dystonia, thoracic outlet syndrome, and piriformis syndrome.
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In addition to having received FDA approval for migraine headaches, some forms of BTx are FDA approved for use in cervical dystonia. Cervical dystonia, also known as spasmodic torticollis, is a cervical spine condition characterized by involuntary contractions of the neck and/or shoulder muscles resulting in abnormal head postures. Neck pain is often an associated symptom in cervical dystonia. BTx injections have been shown in multiple randomized controlled trials to effectively relieve the involuntary contractions, spasms, and pain associated with this condition.50 Thoracic outlet syndrome (which may actually be a variant of cervical dystonia) is another condition in which the use of BTx injections may be indicated. Thoracic outlet syndrome is a controversial diagnosis characterized by neurovascular compression within the thoracic outlet. This condition often results from a combination of hypertonic/dystonic muscles, especially the anterior and middle scalenes. Injecting BTx into these muscles has been shown to effectively relieve the symptoms of thoracic outlet syndrome.51 Although BTx is not FDA approved for the treatment of thoracic outlet syndrome, if the thoracic outlet syndrome is a secondary condition caused by cervical dystonia, then one could make a case for the use of BTx as an FDA approved indication in this scenario. Piriformis syndrome is another controversial diagnosis. It is characterized by sciatic nerve irritation/compression from presumed hypertonicity of the piriformis muscle. Typical patients describe a deep pain in the buttock and can have symptoms that mimic those associated with a classic L5 and/or S1 radiculopathy. Some clinicians refer to piriformis syndrome as pseudosciatica. In addition to piriformis syndrome being a controversial diagnosis, the treatment is similarly controversial, especially with the use of BTx. If priformis syndrome is indeed caused by piriformis hypertonicity, BTx would likely be effective in reducing the hypertonicity and taking pressure off the sciatic nerve. This use is currently off-label, but several studies do demonstrate the effectiveness of BTx for this condition.52,53 Key Points
BTx can be used for various pain diagnoses, including migraines, cervical dystonia, thoracic outlet syndrome, and piriformis syndrome. The use of BTx for pain procedures is often off-label, and its use is considered controversial. SUMMARY
Even in the setting of chronic pain, various injections can still have a useful role in facilitating a rehabilitation program. Spinal injections, such as epidural steroid injections and facet joint injections, are among the most commonly used procedures in pain practices; however a growing number of practices are considering less common injections, such as various TPIs, regenerative injections/prolotherapy, and injections using BTx. REFERENCES
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48. Grayson M. Sterile meningitis after lumbosacral ligament sclerosing injections. J Orthop Med 1994;16(3):98–9. 49. Yun HS, Sun HS, Seon HJ, et al. Prolotherapy-induced cervical spinal cord injury -a case report. Ann Rehabil Med 2012;35(4):570–3. 50. Lew MF, Brashear A, Factor S. The safety and efficacy of botulin toxin type B in the treatment of patients with cervical dystonia. A summary of three controlled trials. Neurology 2000;55(12 suppl 5):529–35. 51. Jordan SE, Ahn SS, Freischlag JA, et al. Selective botulinum chemodenervation of the scalene muscles for treatment of neurogenic thoracic outlet syndrome. Ann Vasc Surg 2000;14(4):365–9. 52. Fishman L, Konnoth C, Rozner B. Botulinum neurotoxin type B and physical therapy in the treatment of piriformis syndrome: a dose-finding study. Am J Phys Med Rehabil 2004;83:42–50. 53. Lang AM. Botulin toxin type B in piriformis syndrome. AM J Phys Med Rehabil 2004;83(3):198–202.
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