Neuropeptides like Substance P and CGRP released during orthodontic tooth movement cause pain but also drive the bone remodeling needed for teeth to move, creating a dilemma where painkillers may slow treatment.
Painkillers may slow orthodontic treatmentNSAIDs reduce orthodontic pain but also suppress the neuropeptide-driven neurogenic inflammation that is essential for bone remodeling and tooth movement, potentially delaying treatment.
What the researchers found
Orthodontic tooth movement activates peripheral sensory nerve endings in the periodontium, which transmit pain signals to the trigeminal spinal nucleus, triggering c-Fos gene expression and concurrent inflammation involving astrocytes, microglia, and neurons.
Activated periodontal sensory fibers release the neuropeptides Substance P and CGRP locally, which induce an inflammatory cascade that is essential for alveolar bone turnover and tooth movement. NSAIDs and other painkillers effectively reduce pain but also suppress this neurogenic inflammatory component, slowing bone turnover and consequently delaying orthodontic treatment progression.
Why it matters
Pain is the most disliked aspect of orthodontic treatment and affects nearly all patients. Understanding that neuropeptides serve a dual role — causing pain while also facilitating the bone remodeling needed for tooth movement — is crucial for developing pain management strategies that don't compromise treatment. This knowledge could guide the development of targeted approaches that control pain without affecting bone turnover.
How the study worked
Narrative review of published research on neurological mechanisms in orthodontic tooth movement, including nerve activation, neuropeptide release (Substance P, CGRP), nerve growth factor and TrkA receptor signaling, trigeminal spinal nucleus processing, neurogenic inflammation, and the effects of pain management on treatment outcomes.
What this study cannot tell us
This is a narrative review that synthesizes existing research without presenting new experimental data. The specific quantitative impact of painkillers on orthodontic treatment duration is not well-established in controlled clinical trials. The review focuses on the neurogenic component of tooth movement without fully addressing other mechanical and cellular factors. Individual patient variation in neuropeptide responses is not discussed.
How to read the evidence
This is a narrative review synthesizing published research on neurogenic mechanisms in tooth movement. It provides a useful conceptual framework but does not present new data, and the clinical impact of painkillers on treatment timing needs more controlled trials.
When this study was published
Published in 2016, this review provides foundational understanding of neurogenic inflammation in orthodontics. The neuropeptide mechanisms described remain relevant and continue to inform current research.
The bigger picture
This review illustrates a broader principle in neuropeptide biology: pain-signaling peptides often have important non-pain functions. Substance P and CGRP are best known as pain mediators, but here they serve as critical regulators of bone remodeling. This dual role is relevant beyond orthodontics — it applies to fracture healing, joint disease, and any condition where neurogenic inflammation influences tissue remodeling.
Questions still open
- Could targeted neuropeptide modulation provide pain relief during orthodontic treatment without slowing tooth movement?
- Are there pain management alternatives to NSAIDs that preserve neurogenic inflammation needed for bone remodeling?
- How much does NSAID use actually delay orthodontic treatment in clinical practice?
Common questions
Why does orthodontic treatment cause pain?
Can taking painkillers during orthodontic treatment actually slow it down?
Read the original research
Neurologic Regulation and Orthodontic Tooth Movement.
Frontiers of oral biology, 18, 64-74
Citation
Kyrkanides, Stephanos; Huang, Hechang; Faber, Richard D. (2016). Neurologic Regulation and Orthodontic Tooth Movement.. Frontiers of oral biology, 18, 64-74. https://doi.org/10.1159/000351900