Scholar: Pilot and Validation Studies ISSN: 2689-7644 Volume 1 Issue 1 Pages: 4 - 10 DOI:10.32778/SPVS.71366.2020.2

Lyftogt perineural injection therapy® as a primary treatment for : a randomized, controlled pilot with crossover

Authors: Eileen Conaway, DO1, Arlene O’Donnell, DO1, Julie Pepe, PhD1, Melissa Pena1

Affiliations: 1) AdventHealth Graduate Medical Education, 7975 Lake Underhill Rd, Suite 210, Orlando, FL 32822

Keywords: plantar fasciitis, Lyftogt perineural injection therapy®, neural prolotherapy, foot pain Downloaded from http://meridian.allenpress.com/scholar/article-pdf/1/1/4/2409945/i2689-7644-1-1-4.pdf by guest on 25 September 2021

Abstract: Background: Plantar fasciitis is a common condition that interferes with patient function and activity level. This study compared usual care to Lyftogt perineural injection therapy® as a primary treatment for plantar fasciitis.

Methods: Subjects with foot pain associated with plantar fasciitis were recruited in to the study. They were randomized into the usual care protocol or treatment with Lyftogt perineural injection therapy®. Subjects in the injection group were injected weekly for 8 weeks. Five milliliters of 5% dextrose in water were injected perineural to the saphenous nerve at the adductor canal and the deep tibial nerve at the bifurcation of the gastrocnemius muscles of the affected side. Subjects who completed the 8 week usual care protocol, crossed over into the injection therapy arm. Subject assessed Roles and Maudsley Scores on a 1-4 scale, physician assessed pain with palpation on a 1-4 scale, and MSKUS measured plantar fasciitis thickness were tracked.

Results: Complete information for 9 control and 9 intervention subjects was compiled. MSKUS measured plantar fasciitis thickness was significantly reduced in the intervention group (p = 0.019). Physician assessed pain with palpation was also significantly reduced for the compiled intervention group (p = 0.006).

Conclusion: Lyftogt perineural injection therapy® may be a viable treatment option for plantar fasciitis.

Article History: Date received: 03/19/2019 Date revised: 06/03/2019 Date accepted: 06/09/2019 Corresponding Author: Eileen Conaway, DO E-mail: [email protected] 1 Introduction: TRPV1 receptor, also known as the capsaicin or 2 21 Plantar fasciitis occurs at a rate of vanilloid receptor.4 The TRPV1 receptor is a ligand- 3 22 approximately 11-15% in the adult US population.1 gated nonselective cation channel involved in the 4 23 Although it is often self-limiting, many patients seek pain response of multiple stimuli including: 5 24 treatment due to pain when weight bearing that endogenous lipids, capsaicin, heat, and low pH.5 6 25 interferes with their activities. Recommended Studies show that activation of this receptor results 7 26 therapy is step-wise and includes the following in the release of calcitonin gene related peptide 8 27 Grade B recommendations: Achilles and plantar (CGRP) and substance P (SP), both products of 9 28 fascia stretching, padding or strapping the foot, neurogenic inflammation.5 10 29 orthotic insoles, oral anti-inflammatories, and Given the success of Lyftogt’s trials with 11 30 corticosteroid injection.1 Achilles tendonitis, this pilot study sought to 12 31 Lyftogt perineural injection therapy® was determine if perineural injection therapy® could be 13 32 developed by John Lyftogt, MD, as a treatment for used as a primary treatment for plantar fasciitis. 14 33 chronic neuropathic pain. It involves a series of 15 34 subcutaneous injections with 5% dextrose in sterile Methods: 16 35 water (D5W) near painful nerves. The initial The study was IRB approved by Florida 17 36 research he published focused on using the therapy Hospital IRB #716933. Subjects were recruited 18 37 as a treatment for Achilles tendonitis.2,3 The from the investigators’ practice, local physical 19 38 proposed mechanism of pain relief is agonism of the 20 4 Lyftogt perineural injection therapy® for plantar fasciitis ISSN: 2689-7644 Volume 1 Issue 1 Pages: 4 - 10 DOI:10.32778/SPVS.71366.2020.2 therapy offices, and community organizations such Figure 1: Flow of Subjects 39 88 as running clubs. Assessed for Eligibility 40 (n = 27) 41 Inclusion Criteria 42 1. Adult age 18 to 85 Excluded (n = 3) 43 Did not meet inclusion criteria (n = 2) 2. Capable of giving informed consent Elected not to participate (n = 1) 44 3. Pain at one or more of the three locations 45 described in “physician assessment of pain” below1 Randomized (n = 24) 46 4. Roles and Maudsley Score6 of 3 or 4 47 5. Available for the study duration 48 Downloaded from http://meridian.allenpress.com/scholar/article-pdf/1/1/4/2409945/i2689-7644-1-1-4.pdf by guest on 25 September 2021

Treatment (n = 12) Control (n = 12) 49 Exclusion Criteria 50 1. to corn 51 3. Any other injection for plantar fasciitis within the 52 duration of the study Lost to follow up (n = 3) Lost to follow up (n = 3) 53 Withdrawn by PI for missing more Withdrawn by PI for missing more 4. Treatment for plantar fasciitis by an outside than 1 study visit than 1 study visit 54 provider within the duration of the study 55 Crossover 5. Children 0-18 56 6. Prisoners 57 7. Pregnant women – urine pregnancy test at Crossover subjects (n = 8) Analyzed (n = 9) 58 screening visit Excluded from analysis (n = 0) Excluded from analysis (n = 0) 59 60 Twenty-seven subjects were recruited into 61 the study and signed informed consent. No data was 62 collected on 3 subjects other than randomization Analyzed (n = 17) 63 assignment and they were therefore discarded prior Excluded from analysis (n = 0) 64 89 to analysis. The average subject age was 51 years old Flow of subjects from screening through analysis. 65 90 (standard deviation 12 years). 18 subjects were PI = Principle Investigator 66 91 female (75%) and 6 subjects were male (25%). The 67 92 average body mass index (BMI) of the subjects was Measures: Subject Assessed Roles and Maudsley 68 93 30 (standard deviation 6.5). Twelve subjects Score6 69 94 randomized to the experimental group and 12 Subjects were asked to give a numerical 70 95 randomized to the control with crossover group. rating from 1-4 based on the scale below. They were 71 96 Subject recruitment, treatment, and follow up took instructed that their rating should reflect the 72 97 place from August 2015 through December 2017. maximum pain they had experienced in the 73 98 preceding week. 74 99 Randomization 75 100 Subjects were randomized to either the Table 1: Subject assessed Roles and Maudsley 76 101 experimental group or the control with crossover score 77 102 group. The randomization was done with equal Point Interpretation 78 treatment allocation of 5 blocks with 20 subjects per Excellent 1 No pain, full movement and activity 79 Occasional discomfort, full movement Good 2 80 block by a statistician using sealedenvelope.com and activity website. Paper slips containing treatment group and 81 study information were placed in sealed envelopes Fair 3 Some discomfort after prolonged activity 82 and delivered to the principal investigator. Study Poor 4 Pain-limiting activities 83 personnel were blinded to the treatment allocation Roles and Maudsley score 1 -4 84 103 until after informed consent was completed. 85 104 105 Records of the randomization assignment were 86 106 retained by the statistician. 87 5 Lyftogt perineural injection therapy® for plantar fasciitis ISSN: 2689-7644 Volume 1 Issue 1 Pages: 4 - 10 DOI:10.32778/SPVS.71366.2020.2

Physician Assessment of Pain Figure 2: Ultrasound Measurement 107 151 Tenderness with palpation at each of three 108 locations: centrally along the plantar fascia, at the 109 plantar medial tuberosity, and the plantar calcaneal 110 tuberosity1 was assessed by the physician on the 111 affected foot or feet. A numerical rating from 1 to 4 112 was assigned based on the scale below. The area of 113 maximum tenderness was considered for data 114 analysis. 115 116 Downloaded from http://meridian.allenpress.com/scholar/article-pdf/1/1/4/2409945/i2689-7644-1-1-4.pdf by guest on 25 September 2021 Table 2: Physician assessment of pain 117 Point Assessed Subject Reaction Excellent 1 No pain Good 2 Painful Fair 3 Painful and winces Ultrasound measurement of the vertical thickness of the 152 Poor 4 Painful, winces and withdraws plantar fascia from the anterior aspect of the inferior border of 153 Pain assessment scale 1 – 4 the calcaneus 118 154 119 155 Plantar fascia thickness via musculoskeletal Figure 3: Injection Sites 120 156 ultrasound (MSKUS) 121 Plantar fascia thickness was measured via 122 SonoSite Edge® with a 6-15 MHz HFL50 linear 123 transducer. All physicians taking the measurements 124 were experienced in MSKUS had been formally 125 trained in MSKUS training courses. Subjects were 126 placed in a prone position with the foot hanging 127 freely off the end of an examination table. 128 Measurements of the vertical thickness of the 129 plantar fascia were made from the anterior aspect of 130 the inferior border of the calcaneus (figure 2).7 The 131 built-in ultrasound caliper tool was used to make the 132 measurements. The plantar fascia was measured at 133 the initial visit, the final visit, and at the cross-over 134 visit for subjects in the control group. 135 Injection Technique 136 Five mLs of D5W were injected targeting 137 perineural to the saphenous nerve at the adductor 138 canal (figure 3, A) and perineural to the deep tibial 139 nerve between the bifurcation of the gastrocnemius 140 muscles (figure 3, B) on the affected leg(s). A: target perineural saphenous nerve at adductor canal (left); B: 141 157 Injections were performed every 7 days (+/-2 days) target perineural deep tibial nerve between the bifurcation of 142 158 the gastrocnemius muscles (right) 159 143 for 8 consecutive weeks. These injections are near 160 144 nerve injections and based on palpatory landmarks Usual Care Protocol, based on ACFAS Clinical 161 145 as described. Dr. Lyftogt does not describe Practice Guidelines: The Diagnosis and Treatment 162 1 146 specifically how close to the nerve the injection of Heel Pain. 163 147 must be given. As a half inch needle is used for all 1. Stretching exercises8 164 148 Lyftogt perineural injection therapy® injections, 2. Home cryotherapy: water bottle distributed 165 149 certainly for deeper nerves the injection could be to subject to fill with water and freeze. The 166 quite a distance away. 150 6 Lyftogt perineural injection therapy® for plantar fasciitis ISSN: 2689-7644 Volume 1 Issue 1 Pages: 4 - 10 DOI:10.32778/SPVS.71366.2020.2

subject was instructed to apply ice to their of initial to final values (2-month time period) 167 216 affect foot/feet at least once daily. within a subject for the intervention period were 168 217 3. Tuli’s classic heel cups™ (bilateral) to be tested using a paired non-parametric comparison 169 218 worn in shoes were distributed to subject. (Wilcoxon-signed rank test). Analysis was based on 170 219 The subject was instructed to wear at all an intention to treat analysis as there were 3 subjects 171 220 times. that did not meet intervention criteria. A 2-tailed p- 172 221 4. Avoid barefoot walking and flat shoes. value less than 0.05 was considered statistically 173 222 5. Limit physical activity. significant. 174 223 6. Oral anti-inflammatory at appropriate 175 224 therapeutic dose. Agent based on patient Results: 176 225 Downloaded from http://meridian.allenpress.com/scholar/article-pdf/1/1/4/2409945/i2689-7644-1-1-4.pdf by guest on 25 September 2021 preference and insurance coverage included: The study collected data on 24 subjects. The 177 226 diclofenac, flurbiprofen, ibuprofen, mean age was 51 (IQR 43 – 58) years with a mean 178 227 ketoprofen, meloxicam, nabumetone, and BMI percentile of 30 (IQR 26 – 33) with female 179 228 naproxen. subjects composing 75% of the study group. 180 229 Complete information for 9 control and 9 181 230 Cross Over intervention subjects was compiled (table 3). 182 231 After 8 weeks, subjects who were enrolled in Subjects with both feet in the study were examined 183 232 the control group crossed over into the treatment and only the primary foot was retained due to the 184 233 protocol if they continue to meet inclusion and correlation of subjective measures. 185 234 exclusion criteria. Once they crossed over, they also 186 235 received the full series of perineural injections every Table 3: Results Control vs. Intervention 187 236 Differences from initial visit Intervention Control seven days (+/- 2 days) for 8 consecutive weeks. All p-value 188 subjects from the control group, except one who to 2-month visit (N=9) (N=9) 189 Mean Difference in plantar 2.0 mm 0.7 mm .019 was lost to follow up, crossed over to the treatment fascia thickness (mm) (decrease) (increase) 190 portion of the protocol. Standard deviation (mm) 2.1 mm 2.2 mm 191 0.4 mm 1.6 mm Median difference (decrease) (increase) 192 Power calculation A numerical decrease 193 8 (89%) 4 (44%) The proposed study sample size was based (benefit) 194 on an equivalence trial for two treatment groups An increase in thickness 1 (11%) 5 (56%) 195 Roles & Maudsley Score .666 using the patient pain score (1 to 4 scale) from (scale 1- 4) 196 baseline to 60-days as the primary outcome measure. A decrease in score (benefit) 4 (44%) 3 (33%) 197 The clinical pain difference of 0.6 points was set as No change 5 (56%) 5 (55%) 198 An increase in score 0 1 (11%) the delta or change. Standard deviation was Physician assessed pain 199 .435 estimated at 1 point for the treatment group and (scale 1-4) 200 one-half point for the control group. Setting A decrease in score (benefit) 4 (44%) 4 (44%) 201 statistical power to 80%, alpha to 0.05 and using a No change 5 (56%) 3 (33%) 202 An increase in score 0 2 (22%) one to one ratio, this study needed 50 subjects per Mann-Whitney test with 95% confidence level 203 237 group to be adequately powered. 204 238 Based on the Mann-Whitney test there is a 205 239 Statistical Methods statistically significant difference in the Plantar 206 240 Continuous variables were summarized as Fasciitis thickness (p=.019) when comparing the 207 241 either mean and standard deviation for normally intervention and control groups with the 208 242 distributed values or median and interquartile range intervention group having an average decrease of 2 209 243 due to the non-normal distribution of values. mm as compared to the control with a 0.4 mm 210 244 Categorical variables were summarized using counts increase. There was no statistical difference in the 211 245 and percentages. Comparison of treatment and physician assessed pain score or the Roles & 212 246 control was tested using Mann-Whitney for Maudsley score when comparing the intervention 213 247 continuous variables and Chi-square test of and control groups. 214 248 independence for categorical variables. Comparison 215 7 Lyftogt perineural injection therapy® for plantar fasciitis ISSN: 2689-7644 Volume 1 Issue 1 Pages: 4 - 10 DOI:10.32778/SPVS.71366.2020.2

Assessing intervention results perineural injection therapy® is a soft tissue 249 283 Seventeen subjects had completed values for injection near a peripheral nerve. 250 284 the treatment period. These subjects include 8 Subject compliance with the usual care 251 285 subjects that were initially in the control group and protocol in the control arm was intentionally not 252 286 crossed over to the intervention (table 4). Compared assessed. Patient adherence to medical therapy is a 253 287 changes during the intervention period was based constant challenge in medicine and studies show 254 288 on Wilcoxon-signed rank test. that human behavior tends to improve when the 255 289 Based on the Wilcoxon signed rank test subject is observed or even thinks they are being 256 290 there is a statistically significant average decrease of observed.11 As the usual care protocol was given as a 257 291 1.3 mm in the plantar fascia thickness when part of a clinical trial it is likely that the subjects 258 292 Downloaded from http://meridian.allenpress.com/scholar/article-pdf/1/1/4/2409945/i2689-7644-1-1-4.pdf by guest on 25 September 2021 comparing the initial visit to the final visit. There were more compliant then a general patient 259 293 was no statistical difference in Roles and Maudsley population would have been. Additionally, the 260 294 score (p=.101). Of the 17 subjects, 9 (53%) reported investigators were unable to identify a method to 261 295 a decrease in score or benefit to the treatment with objectively assess subject compliance with the usual 262 296 the remaining 7 patients (47%) having no change in care protocol. Not assessing compliance in the 263 297 their reported score. There was a significant control group is more translatable to actual clinical 264 298 improvement in general for the physician assessed practice. 265 299 pain score (p=.006) when comparing the initial and The main strength of the study is that of the 266 300 final visits. three endpoints: reduction in Roles and Maudsley 267 301 score, reduction in physician assessed pain score, 268 302 Table 4: Intervention + cross over group and reduction in plantar fascia thickness measured 269 303 Differences from initial visit to Initial Final Visit p-value on MSKUS; the sole objective measurement, 304 the final intervention visit (N=17) Visit 305 Mean Difference in plantar fascia 8.6 7.3 mm .019 decrease in plantar fascia thickness remained thickness (mm) mm statistically significant across all analyses. 306 Standard deviation (mm) 2.4 2.2 Normal plantar fascia thickness measured at 307 Median thickness 9 mm 6.8 mm the calcaneus is 4mm.12 In patients with plantar 308 A numerical decrease (benefit) 14 (82%) An increase in thickness 3 (18%) fasciitis, the plantar fascia becomes thicker although 309 Roles & Maudsley Score .101 the mechanism for this process is unknown. Studies 310 (scale 1- 4) show correlation between pain and increased 311 A decrease in score (benefit) 7 (41%) thickness.13,14 The reduction of 2mm seen in the 312 No change 9 (53%) An increase in score 1 (6%) treatment group is consistent with other studies of 313 Physician assessed pain .006 effective treatment correlating reduction of 314 (scale 1-4) thickness with pain relief.15 There is a lack of 315 A decrease in score (benefit) 9 (53%) No change 8 (47%) consensus regarding the mechanism resulting in the 316 An increase in score 0 thickening of the plantar fascia in people suffering 317 Wilcoxon-signed rank test with 95% confidence level from plantar fasciitis. As this biological process is 270 318 unclear, it is difficult to postulate a mechanism by 271 319 Discussion: which Lyftogt perineural injection therapy® resulted 272 320 An exhaustive literature review was in decreasing the plantar fascia thickness. The 273 321 performed and there are no other studies that have indication for the original study investigating the use 274 322 investigated the use of Lyftogt perineural injection of this therapy was Achilles tendinopathy. As with 275 323 therapy® as a treatment for plantar fasciitis. In plantar fasciitis, Achilles tendonitis/tendinopathy 276 324 addition to Achilles tendonitis it has been studied in was originally though to be an inflammatory process 277 325 knee, shoulder, lateral elbow,9 and .10 but now no longer considered so. Perhaps the 278 326 Although Lyftogt perineural injection therapy® is an underlying mechanism of these non-inflammatory 279 327 injection of dextrose, it is not the same technique as processes are similar given their response to the 280 328 prolotherapy. Prolotherapy injections typically are same therapy. 281 329 either intra-articular or at an enthesis. Lyftogt The postulated mechanism of Lyftogt 282 330 perineural injection therapy® pain relief is agonism 331 8 Lyftogt perineural injection therapy® for plantar fasciitis ISSN: 2689-7644 Volume 1 Issue 1 Pages: 4 - 10 DOI:10.32778/SPVS.71366.2020.2 of the TRPV1, or capsaicin, receptor. The TRPV1 higher powered investigation of this treatment 332 381 receptor is most heavily concentrated on sensory protocol. 333 382 neurons and is implicated in chronic neuropathic 334 383 pain.15,16 The proposed action of dextrose on the Author Contributions: 335 384 TRPV1 receptor is based on its structural similarly All below authors provided substantial 336 385 to mannitol which has been shown to decrease pain contributions to conception and design, acquisition 337 386 due to capsaicin-induced burning pain.17 Dextrose of data, or analysis and interpretation of data. 338 387 has also been shown to improve pain better than 339 388 when compared in trigger point Funding Sources: 340 389 injections.18 An in vitro study to demonstrate This study was funded by a one-time grant 341 390 Downloaded from http://meridian.allenpress.com/scholar/article-pdf/1/1/4/2409945/i2689-7644-1-1-4.pdf by guest on 25 September 2021 agonism of the TRPV1 receptor would be beneficial from Lake Erie College of Osteopathic Medicine. 342 391 in confirming this theoretical mechanism. The purchase of the musculoskeletal ultrasound 343 392 The Roles and Maudsley score was selected machine used in the study was funded by the 344 393 for the subjective patient measurement because it Osteopathic Foundation of East Orlando. 345 394 correlated pain with disability and the investigators 346 395 thought this would lead to more a more meaningful Potential Conflicts of Interest Disclosures: 347 396 measurement than a traditional 1-10 pain scale. In The authors declare no conflict of interest. 348 397 retrospect the small 1-4 scale made it more difficult 349 398 to achieve statistical significance due to the minimal Acknowledgements: 350 399 numeric change between ratings. Additionally, some Authors acknowledge additional investigators: Brian 351 400 subjects commented that although their pain was Browning, DO, Steven Gallas, DO, and Robyn 352 401 improved from baseline, they continued to avoid Young, DO 353 402 activities that had caused pain previously due to fear 354 403 that their pain would return. All subjects in the References: 355 404 treatment group were encouraged to engage in their 1. Thomas JL, Christensen, JC, Kravitz SR, Mendicino 356 405 regular activities, unless limited by actual pain. RW, Schuberth JM, Vanore JV, et al. The diagnosis 357 406 and treatment of heel pain: a clinical practice 407 Furthermore, the sample size was not achieved guideline – revision 2010. J Foot Ankle Surg. 358 408 therefore statistical tests are underpowered 2010;49(3 Suppl):S1-19. DOI: 359 409 therefore, statistical testing was changed to classical 10.1053/j.jfas.2010.01.001. 360 410 detection of clinical differences. 2. Lyftogt, J. Subcutaneous prolotherapy for Achilles 361 411 The injection therapy in this study focused tendinopathy: the best solution? Australasian 362 412 Musculoskeletal Medicine [Internet]. 2007 [cited 2019 413 on the peripheral nerves involved in the pain Aug 16]; 12(2). Available from: 363 414 pattern: the deep tibial and the saphenous nerves. http://www.lyftogtmed.com/assets/Uploads/Subcut 364 415 Recent pain research suggests that the sensitized aneous-prolotherapy-for Achilles-tendinopathy-John- 365 416 spinal segment(s) implicated in a pain pattern must Lyftogt-AMM-Nov-2007-pp-107-09.pdf 366 417 also be addressed for there to be good pain 3. Yelland MJ, Sweeting KR, Lyftogt JA, Ng SK, 367 418 18,19 Scuffham PA, Evans KA. Prolotherapy injections and 419 resolution. Future studies could include applying eccentric loading exercises for painful Achilles 368 420 this idea to Lyftogt perineural injection therapy® for tendinosis: a randomised trial. Br J Sports Med. 2011 369 421 plantar fasciitis and performing additional perineural Apr;45(5):421-428. DOI: 10.1136/bjsm.2009.057968 370 422 injections at relevant dorsal rami of spinal segments 4. Lyftogt J. Chicago neural prolotherapy conference & 371 423 L5-S2. workshop. Title of the conference: 2014 Sep 26-28; 372 424 Chicago, IL. 425 5. Cui M, Honore P, Zhong C, Gauvin D, Mikusa J, 373 426 Conclusion: Hernandez G, et al. TRPVA receptors in the CNS 374 427 Lyftogt perineural injection therapy® for the play a key role in broad-spectrum analgesia of TRPV1 375 428 treatment of plantar fasciitis when compared to antagonists. J Neurosci. 2006 Sep;26(37):9385- 376 429 usual care is non-inferior with regards to subject 9395.DOI: 10.1523/JNEUROSCI.1246-06.2006 377 430 6. Aquil A, Siddiqui MR, Solan M, Redfern DJ, Gulati 431 perceived and physician assessed pain. It may be V, Cobb JP. Extracorporeal shock wave therapy is 378 432 superior in reduction of plantar fascia thickness. A effective in treating chronic plantar fasciitis: A meta- 379 433 larger randomized-controlled trial would allow for a analysis of RTCs. Clin Orthop Relat Res. 2013 380 434 9 Lyftogt perineural injection therapy® for plantar fasciitis ISSN: 2689-7644 Volume 1 Issue 1 Pages: 4 - 10 DOI:10.32778/SPVS.71366.2020.2

Nov;471:3645-3652. DOI: 10.1007/s11999-013- Cell Neurosci. 2015;65:1–10. DOI: 435 492 3132-2 10.1016/j.mcn.2015.02.001 436 493 7. Ahn JH, Lee CW, Kim YC. Ultrasonographic 17. Kim MY, Na YM, Moon JH. Comparison on 437 494 examination of plantar fasciitis: a comparison of treatment effects of dextrose water, saline, and 438 495 patient positions during examination. J Foot Ankle lidocaine for trigger point injection. J Korean Acad 439 496 Res. 2016 Sep;9:38. DOI: 10.1186/s13047-016-0171- Rehabil Med. 1997;21(5):967–73. 440 497 4 18. Shah JP, Thaker N, Heimur J, Aredo JV, Sikdar S, 441 498 8. RelayHealth. Plantar fasciitis exercises. Summit Gerber LH. Myofascial trigger points then and now: 442 499 Medical Group Adult Health Advisor [Internet]. A historical and scientific perspective. PM&R : the 443 500 RelayHealth; 2014 [cited 2019 Aug 16]. Available journal of injury, function, and rehabilitation. 444 501 from: 2015;7(7):746-761. DOI:10.1016/j.pmrj.2015.01.024. 445 502 https://www.summitmedicalgroup.com/library/adult 19. Shah JP. Chronic myofascial pain, spinal segmental 446 503 Downloaded from http://meridian.allenpress.com/scholar/article-pdf/1/1/4/2409945/i2689-7644-1-1-4.pdf by guest on 25 September 2021 _health/sma_plantar_fasciitis_exercises/ sensitization and needling strategies. AAO 447 504 9. Lyftogt J. Subcutaneous prolotherapy treatment of Convocation. 2017 Mar 25. Colorado Springs, CO. 448 505 refractory knee, shoulder and lateral elbow pain. 449 506 Australasian Musculoskeletal Medicine [Internet]. 450 2007 Nov [cited 2019 Aug 16];110-112. Available 451 from: 452 http://www.lyftogtmed.com/assets/Uploads/Subcut 453 aneous-prolotherapy-for-refractory-kneeshoulder- 454 LE-pain-John-Lyftogt-AMM-Nov-2007-pp-110- 455 12.pdf 456 10. Lyftogt J. Prolotherapy for recalcitrant lumbago. 457 Australasian Musculoskeletal Medicine [Internet]. 458 2008 [cited 2019 Aug 16]; 18-20. Available from: 459 http://www.lyftogtmed.com/assets/Uploads/Prolot 460 herapy-for-recalcitrant-lumbago-John-Lyftogt-AMM- 461 May-2008-pp-18-20.pdf 462 11. Van der Linden S. How the illusion of being 463 observed can make you a better person. Scientific 464 American [Internet]. 2011 May [cited 2019 Aug 16]; 465 Available from: 466 https://www.scientificamerican.com/article/how- 467 the-illusion-of-being-observed-can-make-you-better- 468 person/ 469 12. Abul K, Ozer D, Sakizlioglu SS, Buyuk AF, Kaygusuz 470 M. Detection of normal plantar fascia thickness in 471 adults via the ultrasonographic method. J Am Podiatr 472 Med Assoc. 2015;105(1):8-13. DOI: 10.7547/8750- 473 7315-105.1.8. 474 13. Wearing SC, Smeathers JE, Sullivan PM, Yates B, 475 Urry SR, Dubois P. Plantar fasciitis: Are pain and 476 fascial thickness associated with arch shape and 477 loading? Phys Ther [Internet]. 2007 Aug [cited 2019 478 Aug 16];87(8):1002-8. Available from: 479 https://www.ncbi.nlm.nih.gov/pubmed/17553919 480 DOI: 10.2522/ptj.20060136 481 14. Mahowald S, Legge BS, Grady JF. The correlation 482 between plantar fascia thickness and symptoms of 483 plantar fasciitis. J Am Podiatr Med Assoc. 484 2011;101(5):385-9. 485 15. Levine D, Alessandri-Haber N. TRP channels: 486 Targets for the relief of pain. Biochim Biophys Acta. 487 2007;1772(8):989-1003. 488 16. Malek N, Pajak A, Kolosowska N, Kucharczyk M, 489 Starowicz K. The importance of TRPV1-sensitisation 490 factors for the development of neuropathic pain. Mol 491

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