TABLE 2.
Summary of novel treatments for TMD.
| Ref and trails | Novel molecule | Intervention | Efficacy | Mechanism |
|---|---|---|---|---|
| Clemente-Napimoga et al. (2019) | Dioclea violacea lectin | Intravenously injection | Carrageenan/mustard oil induced: anti-inflammatory | 1) Suppressing ICAM-1 2) Blocking the ligands on leukocyte |
| Alves et al. (2018) | Abelmoschus esculentus lectin | Intravenously injection | Zymosan-induced: antinociceptive and anti-inflammatory; Formalin-induced: central antinociceptive |
1) Depending on HO-1 pathway 2) Inhibiting TNF-α and IL-1β 3) Activation of δ and κ opioid receptors but not of μ opioid receptors |
| da Conceição Rivanor et al. (2014) | Caulerpa cupressoides lectin | Intravenous injection | Zymosan-induced: antinociceptive and anti-inflammatory | Inhibiting TNF-α and IL-1β |
| Damasceno et al. (2016) | Lectin of seeds of Artocarpus incisa L./Frutalin | Intraperitoneally injection | Formalin/glutamate/capsaicin induced: antinociceptive | Modulating TRPA1, TRPV1, and TRPM8 receptors |
| Dos Santos et al. (2018),Borgonovo et al. (2020) | Moringa oleifera Lam | Per os | Formalin-induced: antinociceptive and anti-inflammatory (MC-D7, MC-D9, and MC-H) Serotonin-induced: antinociceptive (only MC-H) |
1) Mediation on the inflammatory factors 2) Agonist of TRPA1 |
| Coura et al. (2017) | Gracilaria cornea | Subcutaneous injection | Formalin-induced: antinociceptive Serotonin (5-HT)-induced: No effect |
1) Activating opioid receptor 2) Depending on NO/cgmp/PKG/K + ATP pathway and the HO/CO/cgmp/PKG pathway 3) Inhibiting TNF-α and IL-1β and increasing IL-10 |
| Ribeiro et al. (2020) | Caulerpa racemosa | Intravenous injection | Formalin/capsaicin/serotonin-induced: antinociceptive and anti-inflammatory | 1) Depending on HO-1 pathway 2) Inhibiting TNF-α and IL-1β |
| Araújo et al. (2017) | Solieria filiformis | Subcutaneous injection | Formalin/serotonin-induced: antinociceptive and anti-inflammatory | 1) Activating 3 opioid receptors in the subnucleus caudalis 2) Inhibiting the release of inflammatory mediators in the periarticular tissue |
| do Val et al. (2014); Martinez et al. (2013) | Tephrosia toxicaria Pers | Injection | Zymosan-induced: antinociceptive and anti-inflammatory | 1) Depending on HO-1 pathway 2) Inhibiting TNF-α and IL-1β 3) NO-dependent inhibition of leukocyte recruitment |
| Basu et al. (2019); Barreto et al. (2016); Amora‐Silva et al. (2019); Melo et al. (2019) | Euphorbia bicolor (Euphorbiaceae) latex | Injection into the inflamed vibrissal pad. | CFA-induced: antinociceptive and anti-inflammation | 1) Down-regulating AOPP, ROS, Nox4, 2) Inactivating TRPV1 |
| (−)-α-bisabolol (BISA) | Oral administration | Formalin-induced: antinociceptive and anti-inflammation | 1) Antagonist of TRPA1 2) Inhibiting TNF-α but not IL - 1β |
|
| Melo Júnior et al. (2017) | Eucalyptol | Oral administration | Formalin/mustard oil-induced: antinociceptive | Antagonist of TRPA1 |
| Cady and Durham (2010) | Cocoa | Cocoa-enhanced diet for two weeks | Capsaicin/CFA-induced: antinociceptive and anti-inflammation | 1) Elevating the basal level of MKP-1 and MKP-3 in neurons 2) Inhibiting CGRP 3) Decreasing iNOS |
| Cady et al. (2010) | Grape seed extract | Grape seed extract-enhanced diet for 2 weeks | CFA-induced: antinociceptive | 1) Elevating the basal level of MKP-1 in trigeminal nerve 2) Elevating the basal level of GLAST and decreasing that of CGRP in spinal 3) Suppressing expressions of P-p38, OX-42, and GFAP under CFA-induced pain |
| Magni et al. (2018) | Purple corn extract | Drink purple corn extract for 2 weeks | CFA-induced: antinociceptive | 1) Reducing trigeminal macrophage infiltration 2) Shift of microglia cell polarization to a neuroprotective phenotype |
| Ma et al. (2020) | Resveratrol | Intraperitoneally injection for 4 days | CFA-induced: anti-inflammation | 1) Reversing CFA-caused reduction of SCFAs and recovering CFA-decreased Bacteroidetes and Lachnospiraceae in the gut 2) Rescuing CFA-caused BBB leakage 3) Blocking CFA-enhanced microglial activation and expression of TNF-α in the Sp5C |
|
Dehghan (2015)
NCT02794922 |
Vitamin B complex | Oral administration | Stronger analgesic property than vitamin E and diclofenac | 1) Protecting cell membrane against peroxidation 2) Enhancing norepinephrine and 5-ht 3) Interacting with opioids receptors 4) Regulating the release of NO |
|
Light et al. (2009); Tchivileva et al. (2010)
NCT02437383 |
Propranolol | Oral administration | Suppress alveolar bone loss and osteoclast hyperactivities | Blockage of β-ARs signal pathway |
| Ivković et al. (2018) | Estrogen | Oral administration | Reduce hormonal fluctuation related TMD pain | Inhibiting effects caused by abrupt hormonal changes as following: 1) Fibrocartilage degenerative changes 2) Psychophysical symptoms 3) Abnormal Telper 1 and Telper 2 -mediated response |
|
Kızılcık et al. (2017); Zeng et al. (2016)
NCT03675659 |
Magnesium sulfate | Intra-articular injection | Pain relieving | 1) Blocking NMDA-depended nerve system activities 2) Suppressing calcium entrance 3) Regulating SOX9 expression 4) Immune modulatory effects |
|
Zotti et al. (2019)
NCT03655275 |
Platelet-rich plasma | Intra-articular injection; Combined with arthrocentesis |
Better performance than arthrocentesis alone or combined with HA | 1) Promotes cell proliferation and inhibits nuclear factor-κB ligand (RANKL)–induced osteoclast differentiation 2) Promote cartilage matrix production 3) Increasing HA concentration 4) Stabilizing angiogenesis 5) Anti-inflammatory and regenerative effects |
|
Rahimi-Movaghar and Eslami (2012); Daif (2012); Celakil et al. (2019)
NCT02997410 |
Ozone | Ozonized oil/gas injection Noninvasive form |
Pain relieving | 1) Boosting joint-repairing abilities of fibroblasts 2) Anti-inflammation 3) Chondrogenesis |
|
Christidis et al. (2014); Christidis et al. (2015)
NCT02230371 |
Granisetron | Intramuscular tender-point injections | Pain relieving | 5HT-3 selective serotonin receptor antagonist |
| Thambar et al. (2020) | Botulinum toxin | Intramuscular injections | Controversial | 1) Reducing parafunctional motions 2) Analgesic effect for antagonizing the release of substance P, glutamate, and calcitonin gene regulated peptide |
|
Toth et al. (2010); Giacoppo et al. (2015)
NCT03994640 |
Cannabidiol | Transdermal delivery | Pain relieving | 1) Acting on the CB2 receptors 2) Binding TRPV1, GPR55 and 5-HT-1A 3) Lowering oxidative and nitrosative stress |