Exertional Muscle Soreness / Myalgia in ME/CFS: Mechanism vs DOMS and Management

1 Armstrong 1984 — Mechanisms of Exercise-Induced Delayed Onset Muscular Soreness

Full Citation:: Armstrong RB. Mechanisms of exercise-induced delayed onset muscular soreness: a brief review. Medicine and Science in Sports and Exercise. 1984;16(6):529–538. (Armstrong 1984) PMID:: 6392811 Study Design:: Narrative review of DOMS mechanisms (healthy population) Key Findings::

- DOMS peaks 24–72 h after unaccustomed (especially eccentric) exercise and reflects ultrastructural muscle damage plus a subsequent inflammatory response.
- Lactic acid is cleared within ~1 h of exercise and cannot account for the delayed pain — the explicit correction of the lactate-myth.

Conclusion: Supplies the healthy-person DOMS physiology that is the false comparator patients and clinicians invoke when framing ME/CFS post-exertional muscle pain. Limitations: 1984 narrative review; no ME/CFS data. Certainty Assessment: 0.55 raw × 0.75 (general population) = discounted 0.41

2 Cheung et al. 2003 — DOMS: Treatment Strategies and Performance Factors

Full Citation:: Cheung K, Hume P, Maxwell L. Delayed onset muscle soreness: treatment strategies and performance factors. Sports Medicine. 2003;33(2):145–164. (Cheung, Hume, and Maxwell 2003) DOI:: 10.2165/00007256-200333020-00005 PMID:: 12617692 Study Design:: Seminal review of DOMS mechanism and treatment (healthy/athletic population) Key Findings::

- DOMS arises from mechanical microtrauma and an inflammatory cascade following unaccustomed eccentric load, not lactate accumulation.
- Treatment options (NSAIDs, massage, cryotherapy, stretching, compression) confer only modest/equivocal benefit.

Conclusion: The canonical DOMS mechanism + treatment reference; the false comparator for ME/CFS post-exertional muscle pain. Limitations: General-athletic population; 2003. Certainty Assessment: 0.60 raw × 0.75 (general population) = discounted 0.45

3 Hotfiel et al. 2018 — Advances in DOMS Part I: Pathogenesis and Diagnostics

Full Citation:: Hotfiel T, Freiwald J, Hoppe MW, Lutter C, Forst R, Grim C, Bloch W, Hüttel M, Heiss R. Advances in Delayed-Onset Muscle Soreness (DOMS): Part I: Pathogenesis and Diagnostics. Sportverletzung Sportschaden. 2018;32(4):243–250. (Hotfiel et al. 2018) DOI:: 10.1055/a-0753-1884 PMID:: 30537791 Study Design:: Modern consensus review of DOMS pathogenesis and diagnostics Key Findings::

- DOMS is ultrastructural (sarcomere/cytoskeletal) muscle injury from eccentric/unfamiliar load followed by local inflammation.
- Explicitly decouples soreness from lactate and metabolic acidosis.

Conclusion: The current healthy-person mechanistic baseline against which ME/CFS post-exertional muscle pain must be compared. Limitations: Athletic/healthy focus; no ME/CFS. Certainty Assessment: 0.60 raw × 0.75 (general population) = discounted 0.45

4 Miles & Clarkson 1994 — Exercise-Induced Muscle Pain, Soreness, and Cramps

Full Citation:: Miles MP, Clarkson PM. Exercise-induced muscle pain, soreness, and cramps. Journal of Sports Medicine and Physical Fitness. 1994;34(3):203–216. (Miles and Clarkson 1994) PMID:: 7830383 Study Design:: Classic taxonomy review of exercise-related muscle pain (general population) Key Findings::

- Three entities with distinct etiologies/time courses: (1) pain during/immediately after exercise, (2) DOMS, (3) cramp.
- Separates acute (metabolite/acid-related) from delayed (structural/inflammatory) pain, correcting the lactate misattribution.

Conclusion: Scaffold for asking whether ME/CFS post-exertional myalgia is acute-type, DOMS-type, or a distinct third entity. Limitations: General population; 1994; no ME/CFS. Certainty Assessment: 0.55 raw × 0.75 (general population) = discounted 0.41

5 Ugawa et al. 2002 — ASICs Are Leading Acid Sensors in Human Nociceptors

Full Citation:: Ugawa S, Ueda T, Ishida Y, Nishigaki M, Shibata Y, Shimada S. Amiloride-blockable acid-sensing ion channels are leading acid sensors expressed in human nociceptors. Journal of Clinical Investigation. 2002;110(8):1185–1190. (Ugawa et al. 2002) DOI:: 10.1172/JCI15709 PMID:: 12393854 Study Design:: Human dorsal-root-ganglion nociceptor electrophysiology (in vitro) Key Findings::

- ASICs are the dominant proton (H+) sensors on human primary afferent nociceptors, gated directly by tissue acidosis.

Conclusion: Molecular basis for the proton/acidosis-to-nociceptor arm of exertional muscle pain — the H+ signal ME/CFS muscle hypoperfusion/ischemia would generate, independent of lactate. Limitations: In vitro human DRG; no behavioral/case data. Certainty Assessment: 0.60 raw × 0.40 (in vitro human) = discounted 0.24

6 Chen et al. 2014 — ASIC3, TRPV1, and NaV1.8 in Acute-to-Chronic Muscle Pain

Full Citation:: Chen WN, Lee CH, Lin SH, Wong CW, Sun WH, Wood JN, Chen CC. Roles of ASIC3, TRPV1, and NaV1.8 in the transition from acute to chronic pain in a mouse model of fibromyalgia. Molecular Pain. 2014;10:40. (Chen et al. 2014) DOI:: 10.1186/1744-8069-10-40 PMID:: 24957987 Study Design:: Mouse model of intramuscular acid-induced muscle hyperalgesia Key Findings::

- A single intramuscular acid injection primes muscle nociceptors; a second acid challenge converts acute into long-lasting chronic hyperalgesia, gated by ASIC3, TRPV1, and NaV1.8.

Conclusion: Demonstrates how repeated muscle acidosis — the candidate ME/CFS exertional signal — transitions into chronic myalgia, bridging the Light2009 ASIC3/P2X finding in CFS. Limitations: Animal model; acid injection not physiological exercise. Certainty Assessment: 0.55 raw × 0.50 (animal) = discounted 0.28

7 Lee & Chen 2023 — Myalgia! Where Does It Come From?

Full Citation:: Lee HH, Chen CC. Myalgia! Where does it come from? Acta Neurologica Taiwanica. 2023;32(4):230–239. (Lee and Chen 2023) PMID:: 37967833 Study Design:: Review of myalgia origin and mechanisms (general/fibromyalgia) Key Findings::

- Myalgia (lifetime prevalence ~60–85%) is framed through muscle nociceptor sensitization, acid-sensing (ASIC3/TRPV1) signaling, and peripheral-vs-central contributions.

Conclusion: Mechanistically grounded “where does myalgia come from” scaffold for the ME/CFS muscle-pain-dominant phenotype. Limitations: General review; no dedicated ME/CFS cohort; no DOI. Certainty Assessment: 0.45 raw × 0.75 (general review) = discounted 0.34

8 Goldenberg 2025 — Central Sensitization in Long COVID, FM and ME/CFS

Full Citation:: Goldenberg DL. The pivotal role of central sensitization in long COVID, fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome. Expert Review of Neurotherapeutics. 2025;25(8):973–989. (Goldenberg 2025) DOI:: 10.1080/14737175.2025.2516097 PMID:: 40512228 Study Design:: Authoritative narrative review (long COVID, fibromyalgia, ME/CFS) Key Findings::

- Central sensitization (nociplastic pain) is argued as the unifying pathophysiology across long COVID, fibromyalgia, and ME/CFS, motivating shared management.

Conclusion: Supports a central/nociplastic contribution to ME/CFS myalgia — the mechanism distinguishing it from healthy DOMS (a peripheral, self-limited phenomenon). Limitations: Single-author narrative review; overlap conditions, not pure ME/CFS cohort. Certainty Assessment: 0.50 raw × 0.80 (FM/LC/ME/CFS) = discounted 0.40

9 Wiecha et al. 2025 — Physical Therapies for DOMS: Umbrella Review

Full Citation:: Wiecha S, Cieśliński I, Wiśniowski P, Cieśliński M, Pawliczek W, Posadzki P, Prill R, Zając J, Płaszewski M. Physical therapies for delayed-onset muscle soreness: an umbrella and mapping systematic review with meta-meta-analysis. Sports Medicine. 2025;55(5):1183–1212. (Wiecha et al. 2025) DOI:: 10.1007/s40279-025-02187-5 PMID:: 40120073 Study Design:: Umbrella + mapping systematic review of physical therapies for DOMS Key Findings::

- Consolidates prior (often conflicting) SRs on massage, heat/cold, stretching, compression, and other recovery modalities with effect sizes and confidence.

Conclusion: The best current “what actually helps DOMS” reference to transfer to ME/CFS muscle-soreness management — with the caveat that DOMS is self-limited, not PEM. Limitations: Healthy/athletic population; no ME/CFS. Certainty Assessment: 0.65 raw × 0.75 (general population) = discounted 0.49

10 Davis et al. 2020 — Sports Massage for Performance and Recovery (Meta-analysis)

Full Citation:: Davis HL, Alabed S, Chico TJA. Effect of sports massage on performance and recovery: a systematic review and meta-analysis. BMJ Open Sport & Exercise Medicine. 2020;6(1):e000614. (Davis, Alabed, and Chico 2020) DOI:: 10.1136/bmjsem-2019-000614 PMID:: 32426160 Study Design:: Systematic review + meta-analysis of randomized massage trials Key Findings::

- Massage yields small but significant improvements in DOMS and recovery-related outcomes (flexibility, perceived soreness) with negligible performance effect.

Conclusion: The massage lever for DOMS-relevant muscle-soreness management; in ME/CFS intensity must respect PEM sensitivity. Limitations: Healthy/athletic; heterogeneity; no ME/CFS. Certainty Assessment: 0.65 raw × 0.75 (general population) = discounted 0.49

11 Wang et al. 2021 — Heat and Cold Therapy for DOMS Pain (Meta-analysis)

Full Citation:: Wang Y, Li S, Zhang Y, Chen Y, Yan F, Han L, Ma Y. Heat and cold therapy reduce pain in patients with delayed onset muscle soreness: a systematic review and meta-analysis of 32 randomized controlled trials. Physical Therapy in Sport. 2021;48:177–187. (Wang et al. 2021) DOI:: 10.1016/j.ptsp.2021.01.004 PMID:: 33493991 Study Design:: SR + meta-analysis of RCTs (PROSPERO CRD42020170632) Key Findings::

- Heat and cold both reduce DOMS pain; heat favored for stiffness/blood-flow, cold for acute inflammatory control.

Conclusion: The heat/gentle-thermal-recovery lever most relevant to ME/CFS muscle soreness (low-intensity, non-pharmacologic). Limitations: DOMS (healthy); moderate heterogeneity; no ME/CFS. Certainty Assessment: 0.60 raw × 0.75 (general population) = discounted 0.45

12 Tanabe et al. 2022 — Dietary Supplementation for Muscle Damage and DOMS

Full Citation:: Tanabe Y, Fujii N, Suzuki K. Dietary supplementation for attenuating exercise-induced muscle damage and delayed-onset muscle soreness in humans. Nutrients. 2022;14(1):70. (Tanabe, Fujii, and Suzuki 2022) DOI:: 10.3390/nu14010070 PMID:: 35010943 Study Design:: Review of dietary supplements (tart cherry, polyphenols/antioxidants, curcumin, omega-3) Key Findings::

- Tart cherry (anthocyanin antioxidant/anti-inflammatory) has the most consistent small-to-moderate effect on soreness and strength recovery.

Conclusion: The antioxidant/tart-cherry lever; in ME/CFS the oxidative-stress substrate differs and no ME/CFS tart-cherry trial exists. Limitations: Healthy/athletic; modest effect sizes. Certainty Assessment: 0.55 raw × 0.75 (general population) = discounted 0.41

13 Reno et al. 2022 — Magnesium Supplementation on Muscle Soreness (RCT)

Full Citation:: Reno AM, Green M, Killen LG, O’Neal EK, Pritchett K, Hanson Z. Effects of magnesium supplementation on muscle soreness and performance. Journal of Strength and Conditioning Research. 2022;36(8):2198–2203. (Reno et al. 2022) DOI:: 10.1519/JSC.0000000000003827 PMID:: 33009349 Study Design:: Double-blind between-group RCT (n=22; Mg 350 mg/d for 10 days) Key Findings::

- Magnesium attenuated perceived muscle soreness and some recovery markers vs placebo; performance effects equivocal.

Conclusion: The magnesium lever for DOMS-relevant soreness; ME/CFS magnesium deficiency is separately reported but no ME/CFS soreness RCT exists. Limitations: Small n; athletic population; single study, not independently replicated. Certainty Assessment: 0.55 raw × 0.75 (general population) = discounted 0.41

14 Hill et al. 2017 — Compression-Garment Pressure and Recovery

Full Citation:: Hill J, Howatson G, van Someren K, Gaze D, Legg H, Lineham J, Pedlar C. The effects of compression-garment pressure on recovery after strenuous exercise. International Journal of Sports Physiology and Performance. 2017;12(8):1078–1084. (Hill et al. 2017) DOI:: 10.1123/ijspp.2016-0380 PMID:: 28051341 Study Design:: RCT (n=45) comparing two compression pressures after 100 eccentric drop jumps Key Findings::

- Compression reduced perceived muscle soreness and some muscle-damage markers (CK) during recovery, with little pressure-dependence.

Conclusion: The compression lever for DOMS-relevant soreness — mechanistically most plausible in ME/CFS via the microvascular/capillary-hypoperfusion axis, though untested. Limitations: Healthy active population; short follow-up. Certainty Assessment: 0.55 raw × 0.75 (general population) = discounted 0.41

References

Armstrong, R. B. 1984. “Mechanisms of Exercise-Induced Delayed Onset Muscular Soreness: A Brief Review.” Medicine and Science in Sports and Exercise 16 (6): 529–38.

Chen, Wei-Nan, Cheng-Han Lee, Shing-Hong Lin, Chia-Wen Wong, Wei-Hsin Sun, John N. Wood, and Chih-Cheng Chen. 2014. “Roles of ASIC3, TRPV1, and NaV1.8 in the Transition from Acute to Chronic Pain in a Mouse Model of Fibromyalgia.” Molecular Pain 10: 40. https://doi.org/10.1186/1744-8069-10-40.

Cheung, Karoline, Patria Hume, and Linda Maxwell. 2003. “Delayed Onset Muscle Soreness: Treatment Strategies and Performance Factors.” Sports Medicine 33 (2): 145–64. https://doi.org/10.2165/00007256-200333020-00005.

Davis, Holly Louisa, Samer Alabed, and Timothy James Ainsley Chico. 2020. “Effect of Sports Massage on Performance and Recovery: A Systematic Review and Meta-Analysis.” BMJ Open Sport & Exercise Medicine 6 (1): e000614. https://doi.org/10.1136/bmjsem-2019-000614.

Goldenberg, Don L. 2025. “The Pivotal Role of Central Sensitization in Long COVID, Fibromyalgia and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.” Expert Review of Neurotherapeutics 25 (8): 973–89. https://doi.org/10.1080/14737175.2025.2516097.

Hill, Jessica, Glyn Howatson, Ken van Someren, David Gaze, Hayley Legg, Jack Lineham, and Charles Pedlar. 2017. “The Effects of Compression-Garment Pressure on Recovery After Strenuous Exercise.” International Journal of Sports Physiology and Performance 12 (8): 1078–84. https://doi.org/10.1123/ijspp.2016-0380.

Hotfiel, Thilo, Jürgen Freiwald, Matthias Wilhelm Hoppe, Christoph Lutter, Raimund Forst, Casper Grim, Wilhelm Bloch, Moritz Hüttel, and Rafael Heiss. 2018. “Advances in Delayed-Onset Muscle Soreness (DOMS): Part I: Pathogenesis and Diagnostics.” Sportverletzung Sportschaden 32 (4): 243–50. https://doi.org/10.1055/a-0753-1884.

Lee, Hsun-Hua, and Chih-Cheng Chen. 2023. “Myalgia! Where Does It Come from?” Acta Neurologica Taiwanica 32 (4): 230–39.

Miles, M. P., and P. M. Clarkson. 1994. “Exercise-Induced Muscle Pain, Soreness, and Cramps.” Journal of Sports Medicine and Physical Fitness 34 (3): 203–16.

Reno, Alyssum M., Matt Green, Lauren G. Killen, Eric K. O’Neal, Kelly Pritchett, and Zella Hanson. 2022. “Effects of Magnesium Supplementation on Muscle Soreness and Performance.” Journal of Strength and Conditioning Research 36 (8): 2198–2203. https://doi.org/10.1519/JSC.0000000000003827.

Tanabe, Yoko, Naoto Fujii, and Katsuhiko Suzuki. 2022. “Dietary Supplementation for Attenuating Exercise-Induced Muscle Damage and Delayed-Onset Muscle Soreness in Humans.” Nutrients 14 (1): 70. https://doi.org/10.3390/nu14010070.

Ugawa, Shinya, Takashi Ueda, Yusuke Ishida, Makoto Nishigaki, Yasuhiro Shibata, and Shoichi Shimada. 2002. “Amiloride-Blockable Acid-Sensing Ion Channels Are Leading Acid Sensors Expressed in Human Nociceptors.” Journal of Clinical Investigation 110 (8): 1185–90. https://doi.org/10.1172/JCI15709.

Wang, Yutan, Sijun Li, Yuanyuan Zhang, Yanru Chen, Fanghong Yan, Lin Han, and Yuxia Ma. 2021. “Heat and Cold Therapy Reduce Pain in Patients with Delayed Onset Muscle Soreness: A Systematic Review and Meta-Analysis of 32 Randomized Controlled Trials.” Physical Therapy in Sport 48: 177–87. https://doi.org/10.1016/j.ptsp.2021.01.004.

Wiecha, Szczepan, Igor Cieśliński, Paweł Wiśniowski, Maciej Cieśliński, Wojciech Pawliczek, Paweł Posadzki, Robert Prill, Joanna Zając, and Maciej Płaszewski. 2025. “Physical Therapies for Delayed-Onset Muscle Soreness: An Umbrella and Mapping Systematic Review with Meta-Meta-Analysis.” Sports Medicine 55 (5): 1183–1212. https://doi.org/10.1007/s40279-025-02187-5.