Injections for Chronic Pain a, b c Virtaj Singh, MD *, Andrea Trescot, MD , Isuta Nishio, MD 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, regen- erative 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 Med- icine 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 char- acterized by a myofascial trigger point (MTrP) at muscle, fascia, or tendinous inser- tions. A MTrP is a hyperirritable tender spot, frequently associated with taut band that, on palpation, is firmer in consistency than adjacent muscle fibers. When com- pressed, 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 pmr.theclinics.com 1047-9651/15/$ – see front matter Ó 2015 Elsevier Inc. All rights reserved. 250 Singh et al 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 re- view 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 va- riety 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 end- ings. Central and peripheral antinociceptive properties of BTx have also been postu- lated. 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 ev- idence 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 re- views and meta-analyses of randomized controlled trials suggest that DN is an effec- tive 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 subcu- taneous tissue, then redirected to another area in proximity (Fig. 1). Deep DN to the Injections for Chronic Pain 251 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 fre- quency of sessions, stimulation frequency, and current amplitude to obtain optimal ef- ficacy 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 acupunc- ture 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 acupunc- ture 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 eluci- dated. DN has been shown to diminish spontaneous electrical activity when LTR is eli- cited.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 (noci- ceptor) 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 electrophysio- logic 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 non- noxious sensory input (eg, touch, pressure, vibration) into the CNS can modulate 252 Singh et al 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