This systematic review identified 10 prospective studies (3,343 enrolled teeth) and estimated the frequency of non-odontogenic pain at 6 months or more after root canal treatment to be 3.4% (95% CI: 1.4 to 5.5%). At this rate, with more than 16.4 million root canal treatments performed annually in the United States (21
), each year over half a million endodontic patients would be at risk for non-odontogenic pain.
Non-odontogenic dentolalveolar pain is often difficult to diagnose (5
) because it is poorly understood (22
). Even defining and categorizing such persistent pain is challenging, but conceptually non-odontogenic pain in the dentoalveolar region can arise from 4 potential processes: 1) referred musculoskeletal pain disorder, 2) neuropathic pain disorder, 3) headache disorders presenting in the dentoalveolar region, and 4) a pathological process outside the immediate dentoalveolar region that refers pain to that area, such as sinus disease, salivary gland disorders, brain tumors, angina, throat cancer, and craniofacial vascular disorders (1
In theory, our non-odontogenic pain frequency estimate is an estimate of the incidence of this condition. In practice, because the condition is challenging to diagnose, misclassification at baseline by failing to identify a non-odontogenic reason for pain results in the inclusion of such cases in the reported studies. Misclassified neuropathic pain cases at baseline would be expected to continue to be painful following endodontic treatment (9
), or become more recalcitrant (23
), while non-odontogenic cases of referred pain from distant tissues, such as musculoskeletal, pathological and headache disorders, would likely not be adequately addressed with endodontic treatment. The amount of misclassification is not known, since to our knowledge such research results have not been reported. Furthermore, since patients undergoing endodontic treatment commonly exhibit pre-existing dentoalveolar pain of inflammatory origin (24
), this study cannot differentiate between patients whose non-odontogenic pain arose from pre-existing pathosis and patients whose pain arose from the procedure. Therefore, our estimate represents a mixture of truly incident and remissive cases, as well as maintenance of the condition in patients misclassified at baseline. For this reason we call this estimate a frequency of occurrence, which quantifies the burden of non-odontogenic pain – a condition with many clinical challenges.
The meta-analytical approach allows aggregation of data to produce a robust estimate (11
), but has known limitations based on the quality of the studies included (25
). Therefore, we restricted our meta-analysis to prospective studies, which are thought to produce more accurate results in general (27
) and to endodontic outcome studies in particular (12
). Seven out of the 10 studies identified were published in the last decade, suggesting an increased interest in reporting patient-oriented outcomes and more design rigor in recent endodontic studies. Only one study assessed non-odontogenic pain as its primary outcome. This study found an incidence of 12% (21/175) (15
), a number substantially higher than our meta-analysis summary, which may therefore suggest that our meta-analytic summary estimate is low.
In exploratory analyses, studies with shorter follow-up (6–12 months) had greater frequency of persistent non-odontogenic pain than those with longer follow up, which is an important finding (28
) and may suggest that such persistent pain improves with time. Reduced frequency of persistent post-procedural pain over time has been observed by other studies investigating non-dental surgical models of human pain, such as Caesarean sections (29
) and has been suggested to occur with orofacial pains (23
), but has not been explored in relation to endodontic procedures.
A methodological problem of our review was that the reporting unit was the tooth, whereas the outcome of persistent dentoalveolar pain is a patient-based measure. Teeth within the same individual do not represent statistically independent observations, because they share the same environment, so confidence intervals for our point estimates should be larger than presented. However, we believe that this is not likely a major problem because even though 6 studies reported multiple observations per patient, the difference between the number of patients and the total number of teeth was low (12%; 386/3,343). Another important issue in this review was the large proportion of patients that were not followed (67%; 2,218/3,343), which allows ample opportunity for missing cases of non-odontogenic pain. This is potentially troubling because endodontic patients have been found not to inform their endodontist when persistent pain is present (30
). This is not supported by our meta-regression, which found that studies with <50% follow-up rates had higher pain frequencies than those with ≥50% follow-up rates. This finding, though not statistically significant, is contrary to the common view. Caution needs to be used when interpreting such results since these assessments are exploratory and do not take into account that of the 6 studies having >50% follow-up rate, 4 had the lowest STROBE scores and the above-median STROBE criteria studies had higher frequencies compared to the below-median half.
Our meta-analysis provides some insight about the proportion of persistent pain after endodontic procedures that is non-odontogenic in nature. Combining the present study’s finding with our previous study that estimated the frequency of “all-cause” tooth pain to be 5.3% (12
), non-odontogenic cases may account for 64% (3.4/5.3) of these teeth with pain. When comparing the proportion of patients exhibiting non-odontogenic pain among those determined to have all-cause pain in the 9 studies with available data, the proportion was 56% (44/78). When we use the best single study to assess this proportion, i.e
., the study that used non-odontogenic pain as its primary outcome (15
), this fraction was 57% (21/37). This suggests that at least half of all persistent tooth pain is of non-odontogenic nature, so these cases would best be managed without further endodontic therapy. This is contrary to current opinion (31
) and practice (9
) in dentistry, which advocates retreatment. Regardless of the recommended approach to pain after endodontic treatment, the large proportion of non-odontogenic pain has substantial implications for diagnoses and further treatment of these pain conditions.
In conclusion, 3.4% of patients experienced persistent pain of non-odontogenic origin following root canal therapy – a number that likely represents about half of all persistent “tooth” pains. Therefore, the outcome of non-odontogenic tooth pain is not as rare as commonly assumed. Given that non-odontogenic pain has diverse etiologies and successful treatment is often difficult, further research is needed to diagnose non-odontogenic pain subtypes, quantify the burden on the individual experiencing it, provide adequate treatment, and assess long-term outcomes. Also needed is research that differentiates cases of non-odontogenic pain from those of a local etiology, since tooth-based pathology is amenable to endodontic retreatment and non-odontogenic pain would be best treated if recognized.