Ting K, Huh A, Roldan CJ. Review of Trigger Point Therapy for the Treatment of Myofascial Pain Syndromes. J Anesthesiol & Pain Therapy. 2020;1(3):22-29

Review Article Open Access

Review of Trigger Point Therapy for the Treatment of Myofascial Pain Syndromes Kimberly Ting1, Albert Huh1, Carlos J. Roldan1,2* 1Department of Pain Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 2McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth), Houston, Texas, USA

Article Info Abstract

Article Notes Scope of the investigation: No standard protocol has been established Received: October 08, 2020 for the treatment of (MPS). Invasive therapies such Accepted: November 25, 2020 as and trigger point injection (TPI) with active pharmacological *Correspondence: agents are commonly used. Growing evidence suggests the efficacy of TPI is *Dr. Carlos J. Roldan, Department of Pain Medicine, MD independent of the injectate selected. Normal saline (NS) solution has been Anderson Cancer Center, Houston, Texas, USA; Email: described as an efficient injectate used in TPI for the treatment of MPS. [email protected]. Methods: A broad literature search was performed to compare the use of NS ©2020 Roldan CJ. This article is distributed under the terms of and other pharmacological agents as the injectate in TPI for the treatment of MPS. the Creative Commons Attribution 4.0 International License. Results: We identified 13 reports comparing the safety and efficacy of NS Keywords with that of A or with or without in TPI. Normal saline Trigger point therapy Conclusion: Pain of myofascial origin can be adequately treated with TPI Myofascial pain independent of the injectate used. The use of NS in TPI offers lower cost, safety, and a more favorable side effect profile than other TPI injectates. Introduction Myofascial pain syndrome (MPS) is characterized by painful manifestations originating in the muscles and . The etiology of MPS includes trauma, repetitive muscle strain, physical inactivity, skeletal asymmetry, poor posture, systemic disease, and neuromusculoskeletal lesions1,2. MPS is also thought to be caused by trigger points, taut bands of that can produce local and when provoked1,3,4. Overall, MPS has a lifetime prevalence of up to 85% in the general population and more often affects women between 15 and 40 years of age4,5. In a study by Skootsky et al., the authors found that among the patients who

originated in the myofascial tissue4. The diagnosis of myofascial pain ispresented even more to prevalenta primary in care patients office presenting visit for pain, to a 30% pain hadmanagement pain that clinic, with proportions cited as high as 93% 6. While myofascial pain can be present as the sole pain generator, it is not uncommon for it to be part of a constellation of other pain syndromes. Although the connections are not clearly understood, MPS has been associated with other pain conditions such as 7–9. In patients with MPS, treatment should not be focused on the symptomatic reliefmigraines, of the , myofascial spinal pain pain,alone; and a osteoarthritis comprehensive approach should include managing the underlying conditions and preventing recrudescence of the myofascial pain. Treatment options for MPS range from conservative approaches to invasive procedures. Some studies have shown nonsteroidal

Page 22 of 29 Ting K, Huh A, Roldan CJ. Review of Trigger Point Therapy for the Treatment of Myofascial Pain Syndromes. J Anesthesiol & Pain Therapy. 2020;1(3):22-29 Journal of Anesthesiology and Pain Therapy a comprehensive literature review, Zhou et al. found mixed myofascial pain; however, these are often used in conjunction results when using this agent as the injectate in TPIs16. withnti-inflammatory other treatments drugs6,10 .to Other be an pharmacological effective treatment agents in Previous and recent studies using normal saline for TPI have such as antidepressants, anticonvulsants, and narcotics are shown great results in treating MPS. In a study by Roldan et al., also used to treat myofascial pain, but studies have shown the authors found that normal saline was non-inferior when 11 limits in their effectiveness . A non-randomized study by compared to traditional treatment mixes of local anesthetics Haviv et al. with 42 patients showed that amitriptyline/ plus triamcinolone acetonide15. This calls into question the nortriptyline and gabapentin have been used successfully use of injectates other than normal saline, given that normal in the treatment of myofascial pain; however, these results saline is very inexpensive and has no side effects. This review 12 have not been validated . Other studies have reported that article analyzes the current literature on the effectiveness of home exercises and are both normal saline compared to these other injectates on outcomes effective in reducing pain and can be used as adjuncts in including pain, stiffness, and quality of life. any treatment program6,13. Data Acquisition Invasive procedures aimed at diffusing the trigger point of the muscle that is compromised are extensively A comprehensive search of the literature was performed in September 2020 using the Medline (Ovid), Embase (Ovid), in the treatment of MPS. These include dry needling and and Scopus databases. The search applied both controlled triggerused in pointdifferent injection clinical (TPI). settings Based and on have the theories shown efficacy behind vocabulary and natural language terms for saline, normal the pathophysiology of MPS, mechanical disruption of the saline, trigger point injections, and trigger point therapies. trigger point has emerged as a practical treatment option. Results were limited to English language and human studies In a review by Cummings et al., the authors concluded that published from 2008 to the present. A total of 24 citations and direct needling of myofascial trigger points was an effective treatment14 and abstracts, six were irrelevant to the topic, one was for aabstracts review werearticle, identified one was by for this an search. article Of that those was 24 retracted, citations studies. . This finding has been supported by other and one was for an article that we could not access/obtain, TPIs with various injectates are commonly used to resulting in a total of 15 articles. Of these articles, most treat MPS10. However, numerous authors have called into question the traditional use of local anesthetics mixed with BoNT-A to normal saline, and two compared normal saline in TPIs15,16. Thus, botulinum toxin A (BoNT-A) tocompared local anesthetic local anesthetic plus steroid, to normal the conventional saline, five active compared drug has emerged as an alternative injectate; however, in a mixture (CADM) (Table 1).

Table 1: Overview of the randomized controlled trials in trigger point therapy using injectate included into the review Adverse Type of Anatomical Reference Size Intervention Primary Outcomes Secondary Outcomes events/Side Limitations Study Location effects Double-blind, Group 1: Saline No clear correlation The soft tissue stiffness of random- containing 5 units of between soft tissue No statistically single neck muscles is not Ojala, T. A., ized, and botulinum toxin A stiffness and self-re- significant side Small sam- Neck-shoulder N=31 changed after injections et al. (2010) controlled ported or clinically effects in any ple size of saline or small doses of crossover Group 2: 0.05 mL of assessed pain and groups botulinum toxin A trial normal saline disability Immediately after TPI, the mean pain intensity was Iliocostalis reduced by 5.48 in the NS lumborum, group (p ≤ 0.001) and 5.68 Small iliocostalis in the CADM group (p ≤ sample size. thoracis, 0.001) Overall, the mean Patients quadratus pain scores from prior to the received a Random- lumborum, Group 1: N=23; TPI TPI to ED discharge were heter- ized, paraspinal with normal saline (NS) reduced by 6.17 (p ≤ 0.001) At 2 weeks, the mean No statistically ogenous blinded, - cervical, Roldan, C. J., in the NS arm and 5.96 (p ≤ pain scores were significant side quantity controlled, paraspinal N=48 Group 2: N= 25; et al. (2019) 0.001) in the CADM arm. similar between the effects in any and types non-inferi- - thoracic, 1% 10cc and The size of the effect for the groups groups of pain ority trial paraspinal triamcinolone 40 mg/ NS arm was 2.88, and 1.04 medications - lumbar, piri- mL (CADM) patients would need to re- prior to formis, gluteus ceive treatment to observe the trigger medius, trape- a benefit. The size of effect point injec- zius, latissimus for the CADM arm was 2.51, tions. dorsi and 1.08 patients would

need to receive treatment to observe a benefit.

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Pain was reduced in 87.71% Temporalis of patients injected with sa- muscle for Group 1: N=16 control line and 100% injected with Random- masticatory Small anesthetic. Similar results No statistically ized, con- myofas- Group 2: N=14 normal sample size. Sabatke, S., were obtained for headache significant side trolled, dou- cial pain N=47 saline None Only female et al. (2015) frequency. With regard to effects in any ble-blind syndrome, partici- headache intensity, the in- groups study fibromyalgia, Group 3: N=17 2% pants. jection groups differed from and headache lidocaine the control group, but not

between themselves. Trapezius, gluteus medi- Group 1: TPI with us/minimus, Random- normal saline (NS) No statistically iliocostalis Similar duration of Bakunas, C., ized, dou- N=44 TPI with NS equally as effec- significant side Small sam- thoracislumbo- pain relief at 2-week et al (2015) ble-blinded Group 2: TPI with lido- tive as CADM to treat MPS effects in any ple size rum, quadra- follow-up trial caine/triamcinolone groups tus lumborum, acetate (CADM) paraspinal muscles BoNT-A group expe- rienced statistically significant more days per week without pain at week 4 and statistically significant more days per week with no or mild pain at week 8. Optimal Duration of daily pain dose reduced in BoNT-A and time group compared with course of Group 1: N=81 TPI NS at weeks 9 and 10. Random- No significant difference in treatment with botulinum toxin A BoNT-A group had No statistically ized, dou- Cervical, improvement at week 5. Sig- effects not Benecke, R., (BoNT-A) statistically significant significant side ble-blinded, shoulder N=153 nificant difference at week 8 yet estab- et al (2011) reduced mean num- effects in any placebo-con- muscles with greater improvement in lished; thus Group 2: N=72 TPI with ber of trigger points. groups trolled trial group receiving BoNT-A may not normal saline (NS) Pain intensity for have been all trigger points appropri- was statistically ate for all significantly lower patients. in the BoNT-A group compared to NS from week 4 to week 12. Physcians’ global assessment, patients’ global assessment statistically favored BoNT-A over placebo at weeks 8 and 12. Cannot account for different location of anterior Lidocaine group showed cutaneous statistically significant- nerve ly higher proportion of Ability to predict entrapment Random- Group 1: N=24 TPI with patients achieving at least the type of injection in patients, ized, dou- No statistically lidocaine lidocaine 1% 50% improvement in pain administered based Boelens, OB, ble-blind, Abdominal N=48 significant side may not perception on VAS and/ on observed effect et al (2013) place- wall effects in any have Group 2: N=24 TPI or an improvement of at 15-20 min after TPI bo-con- groups reached ex- with NS least 2 points on VRS during (clinician 36/44, trolled trial act point of physical examination 15-20 patients 26/48) entrapment min after TPI compared with as freehand before injection technique used, short follow-up duration (15-20 min)

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Random- No statistically significant Group 1: N=20 TPI ized, dou- difference in tenderness to Small with botulinum toxin A No statistically ble-blind, Trapezius, , visual analogue sample size, Carroll, A., et (BoNT-A) significant side place- splenius N=37 pain scale, Vernon-Mior None possible al. (2008) effects in any bo-con- capitis Neck Pain and Disability insufficient Group 2: N=17 TPI with groups trolled Index, and cervical range of toxin normal saline (NS) study motion Placebo effect, small sample size, limited gen- eralizability, No significant dif- multiple Dou- Group 1: N=30 TPI No difference in partic- ferences in pain on clinicians ble-blind, botulinum toxin A No statically ipant-reported pain on palpation at 4 and 12 adminis- Dessie, SG, randomized, Pelvic floor N=59 (BoNT-A) significant side palpation of the most weeks. No significant tering the et al (2019) place- muscles effects in any painful pelvic floor muscle at difference reported injections, bo-con- Group 2: N=29 TPI with groups 2 weeks pain on visual ana- follow-up trolled trial normal saline (NS) logue scale. limited to 12 weeks, presence of multiple pain disor- ders Dou- Decreased number Group 1: N=22 TPI with Patients receiving bupi- ble-blind, of trigger points and No statistically vacaine did not report a Giladi, H, et randomized, Lower back increase in median significant side Small sam- N=43 benefit at the end of the al (2014) paral- muscles pressure algometry effects in any ple size Group 2: N=21 TPI with study compared to patients lel-group measurements in groups normal saline receiving normal saline clinical trial both groups BoNT-A group reported greater reductions in head- Dou- Group 1: N=12 TPI ache frequency during the No significant dif- ble-blind, Trapezius, with botulinum toxin A first part of the study, but ference in range of No statistically randomized, sternocleido- Harden, RN, N=23 (BoNT-A) these effects dissipated by motion planes, trig- significant side Small sam- place- mastoid mus- et al (2009) week 12. ger point threshold, effects in any ple size bo-con- cle, splenius Group 2: N=11 TPI with Reductions in headache and psychological groups trolled capitis normal saline (NS) intensity over time did not measures clinical trial differ significantly between groups Group 1: N=27, TPI with normal saline (NS) The group that received 5 Dou- Frontal, tem- Group 2: N=27, TPI lidocaine injections had sig- ble-blind, poral, mas- Small with 0.5% lidocaine nificantly reduced frequency No statistically randomized, seter, SCM, sample Karadas, O, and severity of pain at 2, significant side place- semispinalis N=108 None size, short et al (2013) Group 3: N=27, TPI 4, and 6 months based on effects in any bo-con- capitis, trape- duration of with NS x 5 doses visual analogue scores and groups trolled zius, splenius follow-up frequency of painful days clinical trial capitis Group 4: N=27, TPI per month with 0.5% lidocaine x 5 doses Muscles Lidocaine group had statis- Dou- innervated tically significant decrease ble-blind, by C1-C3 and Group 1: N=24 TPI with in number of painful days No statistically randomized, trigeminal lidocaine 0.5% Karadas, O, N=48 in a month, visual analogue significant side Small sam- place- nerve, exit None et al (2013) scale, amount of analgesic effects in any ple size bo-con- points of /CN Group 2: N=24 TPI with use in month, Hamilton groups trolled V, and around normal saline (NS) depression score, and Hamil- clinical trial superior cervi- ton anxiety score cal ganglion

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Visual analogue scale (VAS) and frequency of painful days per month (FPD) were significantly improved in Groups 2, 4, and 5 at post-treatment months 2 Group 1: N = 24 TPI and 4, and this improvement with normal saline remained in Groups 4 and 5 (NS) at the MTrPs. in post-treatment month 6 Group 2: N=24 TPI with Compared with Group 1, 0.5% lidocaine at the Group 2 had significantly im- MTrPs. proved VAS and FPD scores Group 3: N=24 TPI with at post-treatment months 2, Small Random- NS at Point E. No statistically 4, and 6 sample Xie, P., et al. ized, Trapezius N=120 Group 4: N=24 TPI significant side Compared with Group 3, None size, short (2015) blinded, muscle with 0.5% lidocaine at effects in any Group 4 showed significantly follow-up controlled Point E. groups improved treatment out- period Group 5: N=24 TPI with comes in terms of the VAS 0.5% lidocaine at both and FPD scores at post-treat- Point E and Point F ment months 2, 4, and 6 Each group received Compared with Group 2, injections once a week the VAS and FPD scores for 4 weeks. improvement persisted at post- treatment month 6 in Group 4 Compared to Group 4, Group 5 had better VAS and FPD scores at post-treat- ment months 2, 4, and 6

TPI: trigger point injection, CADM: conventional active drug mixture, SCM: sternocleidomastoid, CN V: fifth cranial nerve, C: cervical.

Pathophysiology of Trigger Points Local Anesthetic with or without Steroid Several theories exist about the proposed Compared with Normal Saline pathophysiology of trigger points. One involves the The theory behind using local anesthetic in TPIs sensitization of nerve fibers, whereby persistent sensory involves desensitization of free nerve endings, local input at dysfunctional peripheral nerve endplates leads vasodilation, and inhibition of the propagation of pain by to central sensitization in the spinal cord. This in turn its effect on sodium channels and thus endplate potentials. causes expansion of the affected dorsal horn neuron, The theory behind adding a steroid to TPIs is that the anti- creating referred regional pain that does not follow a dermatomal pattern, as seen in MPS17,18. Another and prevent progression to central sensitization21,22. theory suggests that prolonged muscle contraction is an inflammatory effect can decrease peripheral sensitization The historically used injectate of lidocaine with or offending mechanism, resulting in local tissue ischemia without the use of steroids has been extensively studied. and the accumulation of metabolic byproducts. These Karadas et al. found that lidocaine was more effective than events perpetuate a cycle of motor and sympathetic normal saline in TPIs for pain relief in patients suffering activity that leads to a pain response, which can persist from chronic tension-type headaches. In this double-blind even after removal of the initial stimulus19. Given these study, patients were randomized to receive TPIs with proposed pathophysiology’s of MPS, it is believed that either normal saline or lidocaine 0.5% once every 3 days mechanical disruption with a needle, with or without for three injections and then evaluated 3 months after injectate, is necessary to terminate the nerve endplate treatment. While both groups experienced statistically dysfunction and allow for prolonged pain relief6. Additionally rapid pain relief is seen after TPIs compared analogue scale values, amount of analgesic used in a to non-invasive treatment, thus obligating the use of month,significant Hamilton decreases Depression in number Rating of painful Scale days,scores, visual and TPIs over other treatments20. Hamilton Anxiety Rating Scale scores, the lidocaine group When looking at different injectates for TPIs, the three responded to treatment better than the normal saline mainstays used in current practice are lidocaine with or without steroid, BoNT-A, and normal saline. Researchers p<0.001 23. This difference could potentially be explained bygroup the inincreased all categories, frequency with of athe statistical injections, significance and on the of MPS with mixed results. have compared the efficacy of these different injectates in location of the TPIs, however, which in addition to specific

Page 26 of 29 Ting K, Huh A, Roldan CJ. Review of Trigger Point Therapy for the Treatment of Myofascial Pain Syndromes. J Anesthesiol & Pain Therapy. 2020;1(3):22-29 Journal of Anesthesiology and Pain Therapy muscle groups included injections at the exit points of with triamcinolone 40 mg/mL in a 9:1 ratio as the CADM ganglion. An unintentional nerve block at these locations pain score on a numeric rating scale (p<0.001). In addition, the fifth cranial nerve and around the superior cervical sizeresulted of effect in statistically and number significant needed reductions to treat were in the similar mean outcomes compared to normal saline. between the two groups, demonstrating that normal saline could confound the finding that lidocaine offered superior is non-inferior to CADM in reducing pain. At the 2-week Following that study, Karadas et al. looked to see if follow-up, the mean pain score, size of effect, and number repeated injections offered improved outcomes in patients with tension-type headaches in a double-blind study. needed to treat remained similar, suggesting that the type 15 Patients were randomized into four groups: 1. one injection of injectate used was irrelevant .

conducted by Sabatke et al., where patients were randomized injectionsof normal ofsaline, lidocaine 2. one 0.5% injection on alternate of lidocaine days. 0.5%, They 3.found five to TPIsSimilar with findings normal weresaline, seen lidocaine in a double-blind2%, or control study (no thatinjections the lidocaine of normal groups saline statistically on alternate outperformed days, and 4. fivethe injections). Both the normal saline and lidocaine groups normal saline groups at each time interval in the measured outcomes of frequency of painful days per month and intensity, and weekly headache frequency compared to the visual analogue scale (p<0.05). Additionally, the group that controlhad significantly group (p<0.05); reduced however, facial painthe injectate intensity, groups headache did not differ amongst themselves27. While there continues to had persistent improvement at 6 months. Interestingly, be evidence that TPIs are effective in treating myofascial received five injections of lidocaine was the only group that pain, multiple researchers have shown that there is no injections compared to one had better outcomes regardless difference in outcomes associated with type of injectate28. ofthis the study injectate, also showed which maythat pointthe groups to the thatutility received of using five a series of injections for MPS24. Unlike the previous study, Botulinum Toxin Compared with Normal Saline TPIs in this study were performed in targeted muscles and Botulinum toxins, most commonly BoNT-A, have come not near nerve exit points, thus decreasing the possibility into favor as potential therapeutic injectates for TPIs. of a direct nerve block confounding the results. The toxins act by blocking the presynaptic release of The utility of lidocaine in TPIs compared to normal acetylcholine from motor and autonomic nerve endings, saline is further illustrated in a study by Boelens et al., leading to inhibition of skeletal muscle contraction where researchers compared the effect of a single TPI using lidocaine 1% or saline to diagnose anterior cutaneous antinociceptive and muscle-relaxant properties, which and flaccid paralysis. This accounts for the toxins’ nerve entrapment syndrome in patients suffering from have been utilized clinically for the treatment of MPS and abdominal pain. Unsurprisingly, patients who received other musculoskeletal disorders. Several studies have been performed to assess the an improvement of at least 50% in the visual analogue role of botulinum toxins in TPIs. In a study by Benecke et scalelidocaine score demonstrated and/or an improvement a successful ofresponse, at least twodefined points as on a pain verbal rating scale; patients who received saline patients with MPS of the cervical and/or shoulder muscles. 25 (p=0.007) . Subjectsal., the efficacy were randomized of TPIs with into BoNT-A either was the investigated intervention in This study, along with others, again demonstrates group (BoNT-A injectate) or the control group (normal that if nerve endings are blocked either intentionally saline injectate). Results from this study did not show or unintentionally there will be improved outcomes26. However, in this study, patients received a larger injectate at week 5, with 37/76 (49%) patients in the BoNT-A group volume, 10cc, than is typically used in TPIs, and this high showingsignificant response improvement to treatment with BoNT-A compared compared to 27/72 to (38%)saline regard to follow-up, patients were only reassessed 15 to improvements in pain intensity compared to baseline were 20volume minutes of injectate after the could TPI, and have thus acted the likelong-term a field utilityblock. for In onlyin the seen control in week group 8 and (p=0.1873). were greater Statistically in the BoNT-A significant group pain control cannot be determined. Furthermore, in this than in the control group (p=0.008). Furthermore, duration of daily pain was reduced in the BoNT-A group from week patients with MPS typically have multiple trigger points, study patients only identified one trigger point, whereas groups were only seen at weeks 9 and 10 (p=0.04)29. 5, but statistically significant differences between the two Carroll et al. looked at BoNT-A in comparison to normal makingThere the are results also of a this number study difficultof studies to generalize. showing that normal saline is a viable alternative to the traditional saline placebo TPIs for whiplash-associated disorder. Both injectate of local anesthetic with or without steroid. groups displayed improvement in pain scores, Vernon- Roldan et al. demonstrated in a single-blind, randomized Mior Neck Pain and Disability Index scores, and cervical study that TPIs with both normal saline and lidocaine 1% range of motion at the 4-week and 3-month marks after

Page 27 of 29 Ting K, Huh A, Roldan CJ. Review of Trigger Point Therapy for the Treatment of Myofascial Pain Syndromes. J Anesthesiol & Pain Therapy. 2020;1(3):22-29 Journal of Anesthesiology and Pain Therapy treatm pain severity, and range of motion, are compared. This differences between the two groups. The study concluded lack of evidence, as well as the high cost of a single BoNT-A that BoNT-Aent, but was therenot superior were noto placebo statistically in regard significant to the injection, makes it a poor injectate choice34. outcomes measured, claiming that a larger sample size of Lidocaine with or without steroid has had mixed results at least 140 patients was needed to achieve statistically 30. conclude from the studies is that local anesthetic is superior in terms of efficacy for patients with MPS. What we can significantTPIs have results also been utilized in the treatment of to normal saline only when nerve endings are either myofascial pelvic pain, as seen in Dessie et al., where the intentionally or unintentionally targeted. Beyond that, the difference between BoNT-A and normal saline TPIs in saline are equivocal, with some studies demonstrating that normalefficacy salineof TPIs is withnon-inferior local anesthetic to CADM. compared to normal pelvic floor muscles was evaluated. Results showed that at between the two groups in subject-reported pain upon However, when comparing the potential side effects 2 weeks after treatment there was no significant difference and cost of CADM to normal saline, normal saline has clear in the BoNT-A group reported greater declines in pelvic advantages over CADM. Steroid used in CADM can cause palpation of most of the pelvic floor muscles. While subjects pain at 4 and 12 weeks on the visual analogue scale, these local skin thinning, muscle atrophy, and systemic effects such as dysregulation of hormone balance, decreased bone both time points). Furthermore, the Pelvic Floor Distress density, and uncontrolled blood glucose. Local anesthetic differences were also not statistically significant (p=0.16 at 31 group over the BoNT-A group at 2 weeks (p=0.01) . and in patients with allergies, thus the main downside is Inventory score was significantly improved in the placebo BoNT-A has also seen expanding application in the cost.has a Somelow side studies effect do profile show except that TPIs in intravascular with local anesthetic injection management of headaches. Harden et al. assessed the can decrease post-injection soreness; however, there are value of BoNT-A as a prophylactic treatment for chronic tension-type headaches with referred head pain in the no additional long-term benefits. cervical musculature. In this randomized, double-blind in patients who, based on the natural history of myofascial study, participants received either BoNT-A or normal saline pain,These will most are notlikely insignificant need repeated considerations, injections. Thus, especially based placebo injections in cervical myofascial trigger points. There were greater reductions in headache frequency with BoNT-A compared to placebo (p=0.013); however, agenton efficacy, in TPIs. side effect profile, and cost, we believe that these effects declined by week 12. Decreased headache normal saline should be considered one of the first-line Limitations and Future Directions groups (p=0.80). There were no differences between the In reviewing the current literature on TPIs and groupsintensity in wasany notof the significantly secondary differentoutcome betweenmeasures, the which two myofascial pain there are a number of limitations, including, included cervical range of motion, trigger point threshold, but not limited to, small sample sizes and differences in and psychological assessment. Thus, the use of BoNT-A for local anesthetic type, volume, and concentration used; tension-type headaches yielded mixed results, and further technique employed, such as location of TPIs and size of needle used; post-treatment management; duration this disorder32. studies are needed to assess the toxin’s true efficacy for Conclusion TPI. Further studies elucidating these differences would strengthenand location the of literature pain symptoms; on the use and of TPIsvisual in verification the treatment of Some postulate that the simple dilution of pain of MPS. mediators such as substance P, cytokines, and calcitonin gene-related peptide with any injectate, irrespective of the Conflict of Interest type, mediates pain relief33. Given this concept and multiple studies showing no difference in clinical outcomes between different injectates, we suggest the best way to select an AcknowledgmentAuthors report no conflicts of interest. The authors want to acknowledge the contribution of injectateAccording is based to theon side mechanism effect profiles of action and cost.of BoNT-A, it should be an effective treatment for MPS and has been Anderson Cancer Center for their assistance with editing. the scientific editors in the Research Medical Library at MD used effectively for other pain syndromes. 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