Comparison of Pain-Generated Functional Outcomes in Experimental Models of Delayed-Onset Muscle Soreness and Nerve Growth Factor Injection of the Masticatory Muscles

Zhang, Yuanxiu; Exposto, Fernando G.; Grigoriadis, Anastasios; Lobbezoo, Frank; Koutris, Michail; Zhang, Jinglu; Wang, Lin; Svensson, Peter

doi:10.11607/ofph.2623

Cited by 5 publications

(4 citation statements)

References 39 publications

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“…Using eccentric muscle training (lengthening muscle contractions) will typically induce hyperalgesia and low to moderate pain during function with a maximum pain intensity appearing 1 to 2 days after the exercise. 53,73,153,193,222,269 Animal studies have found that intramuscular endogenous NGF may be fundamental for the delayed-onset muscle soreness induced by eccentric training. 166,247 Intramuscular NGF injections do not excite dorsal horn neurons but rather subthreshold excitatory potentials and sensitisation after 1 day, which is opposite to the effects of intramuscular injections of hypertonic saline, 97,237 and hyperexcitability of dorsal horn neurons is more pronounced after 2 NGF injections.…”

Section: Localised Hyperalgesiamentioning

confidence: 99%

“…5). 4,5,7,28,36,45,46,59,68,90,122,152,153,170,199,209,213,229,230,234,235,257,262,269 Similarly, injection of NGF into the infrapatellar fat did not evoke pain at injection but rather hyperalgesia after 1 day. 165 More intense NGF-induced muscle pain and hyperalgesia have been reported in women compared with men, and expression of N-methyl-D-aspartate receptors on peripheral nerve fibres may partly explain the long-term hyperalgesia and pain, particularly in women.…”

Section: Introductionmentioning

confidence: 96%

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Mechanisms and manifestations in musculoskeletal pain: from experimental to clinical pain settings

Graven‐Nielsen

2022

Pain

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Section: Localised Hyperalgesiamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Mechanisms and manifestations in musculoskeletal pain: from experimental to clinical pain settings

Graven‐Nielsen

2022

Pain

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“…CFA causes severe inflammation, which is similar to myositis leading to such signs as edema, erythema or rubor. The prevailing evidence show that TMDM is seldomly accompanied by myositis 13 , 14 . Hence, CFA intra-muscular injection does not optimally represent TMDM.…”

Section: Introductionmentioning

confidence: 99%

Associations of tissue damage induced inflammatory plasticity in masseter muscle with the resolution of chronic myalgia

Lindquist,

Shein,

Hovhannisyan

et al. 2023

Sci Rep

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Gene plasticity during myogenous temporomandibular disorder (TMDM) development is largely unknown. TMDM could be modeled by intramuscular inflammation or tissue damage. To model inflammation induced TMDM we injected complete Freund’s adjuvant (CFA) into masseter muscle (MM). To model tissue damage induced TMDM we injected extracellular matrix degrading collagenase type 2 (Col). CFA and Col produced distinct myalgia development trajectories. We performed bulk RNA-seq of MM to generate gene plasticity time course. CFA initiated TMDM (1d post-injection) was mainly linked to chemo-tacticity of monocytes and neutrophils. At CFA-induced hypersensitivity post-resolution (5d post-injection), tissue repair processes were pronounced, while inflammation was absent. Col (0.2U) produced acute hypersensitivity linked to tissue repair without inflammatory processes. Col (10U) generated prolonged hypersensitivity with inflammatory processes dominating initiation phase (1d). Pre-resolution phase (6d) was accompanied with acceleration of expressions for tissue repair and pro-inflammatory genes. Flow cytometry showed that immune processes in MM was associated with accumulations of macrophages, natural killer, dendritic and T-cells, further confirming our RNA-seq findings. Altogether, CFA and Col treatments induced different immune processes in MM. Importantly, TMDM resolution was preceded with muscle cell and extracellular matrix repairs, an elevation in immune system gene expressions and distinct immune cell accumulations in MM.

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“…Several studies have used intramuscular injection of NGF into the masseter muscle to mimic pain and dysfunction associated with TMD in otherwise healthy humans, showing the development of mechanical allodynia, hyperalgesia, pain on function and functional limitation [10][11][12][13][14][15] . However, these studies have included relatively small numbers of participants (ranging from n=14-30).…”

Section: Introductionmentioning

confidence: 99%

Intramuscular injection of nerve growth factor as a model of temporomandibular disorder: nature, time-course, and sex differences characterising the pain experience

Schabrun

Millard

et al. 2022

Preprint

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Background: Temporomandibular disorder (TMD) is a common condition that frequently transitions to chronic symptoms. Experimental pain models that mimic the symptoms of clinical TMD may be useful in understanding the mechanisms, and sex differences, present in this disorder. Here we aimed to comprehensively characterise the nature and time-course of pain, functional impairment and hyperalgesia induced by repeated intramuscular injection of nerve growth factor (NGF) into the masseter muscle, and to investigate sex differences in the NGF-induced pain experience. Methods: 94 healthy individuals participated in a longitudinal observational study with 30-day follow-up. NGF was injected into the right masseter muscle on Day 0 and Day 2. Participants attended laboratory sessions to assess pain (Numerical Rating Scale; NRS), functional limitation (mouth opening distance, Jaw Functional Limitation Scale; JFLS) and mechanical sensitization (pressure pain thresholds; PPTs) on Days 0, 2 and 5 and completed twice daily electronic pain dairies from Day 0 to day 30. Results: Peak pain averaged 2.0/10 (95 % CI: 1.6-2.4) at rest and 4.3/10 (95 % CI: 3.9-4.8) on chewing. Pain-free mouth opening distance reduced from 5.0 cm (95 % CI: 4.8-5.1 cm) on Day 0 to 3.7 cm (95 % CI: 3.5-3.9 cm) on Day 5. The greatest reduction in PPTs was observed over the masseter muscle. Females experienced higher pain, greater functional impairment, and greater sensitivity to mechanical stimuli than males. Conclusion: Intramuscular injection of NGF is a useful model with which to explore the mechanisms, and sex differences, present in clinical TMD.

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Comparison of Pain-Generated Functional Outcomes in Experimental Models of Delayed-Onset Muscle Soreness and Nerve Growth Factor Injection of the Masticatory Muscles

Cited by 5 publications

References 39 publications

Mechanisms and manifestations in musculoskeletal pain: from experimental to clinical pain settings

Mechanisms and manifestations in musculoskeletal pain: from experimental to clinical pain settings

Associations of tissue damage induced inflammatory plasticity in masseter muscle with the resolution of chronic myalgia

Intramuscular injection of nerve growth factor as a model of temporomandibular disorder: nature, time-course, and sex differences characterising the pain experience

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