Altered pain modulation in patients with persistent postendodontic pain

Cibele Nasri-Heir, Junad Khan, Rafael Benoliel, Changyong Feng, David Yarnitsky, Fengshen Kuo, Craig Hirschberg, Gary Hartwell, Ching-Yu Huang, Gary Heir, Olga Korczeniewska, Scott R Diehl, Eli Eliav, Cibele Nasri-Heir, Junad Khan, Rafael Benoliel, Changyong Feng, David Yarnitsky, Fengshen Kuo, Craig Hirschberg, Gary Hartwell, Ching-Yu Huang, Gary Heir, Olga Korczeniewska, Scott R Diehl, Eli Eliav

Abstract

Persistent pain may follow nerve injuries associated with invasive therapeutic interventions. About 3% to 7% of the patients remain with chronic pain after endodontic treatment, and these are described as suffering from painful posttraumatic trigeminal neuropathy (PTTN). Unfortunately, we are unable to identify which patients undergoing such procedures are at increased risk of developing PTTN. Recent findings suggest that impaired endogenous analgesia may be associated with the development of postsurgical chronic pain. We hypothesized that patients with PTTN display pronociceptive pain modulation, in line with other chronic pain disorders. Dynamic (conditioned pain modulation, temporal summation) and static (response to mechanical and cold stimulation) psychophysical tests were performed intraorally and in the forearm of 27 patients with PTTN and 27 sex- and age-matched controls. The dynamic sensory testing demonstrated less efficient conditioned pain modulation, suggesting reduced function of the inhibitory endogenous pain-modulatory system, in patients with PTTN, mainly in those suffering from the condition for more than a year. The static sensory testing of patients with PTTN demonstrated forearm hyperalgesia to mechanical stimulation mainly in patients suffering from the condition for less than a year and prolonged painful sensation after intraoral cold stimulus mainly in patients suffering from the condition for more than a year. These findings suggest that PTTN is associated more with the inhibitory rather than the facilitatory arm of pain modulation and that the central nervous system has a role in PTTN pathophysiology, possibly in a time-dependent fashion.

Conflict of interest statement

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Figures

Figure 1
Figure 1
Conditioned pain modulation in 27 patients suffering from painful posttraumatic trigeminal neuropathy (PTTN) and 27 healthy controls. Results show intraoral evaluations in the subjects' affected (injured) and contralateral trigeminal sites and on the dominant forearm. Data are presented as mean ± SD. Nonparametric analysis was used to compare the difference between study groups. The exact Wilcoxon rank sum test was used to compare the medians of 2 groups (PTTN and control), and the exact Kruskal–Wallis test was used to compare the medians across multiple groups (PTTN > 1 year, PTTN

Figure 2

The raw data used to…

Figure 2

The raw data used to calculate temporal summation and conditioned pain modulation (presented…

Figure 2
The raw data used to calculate temporal summation and conditioned pain modulation (presented in Fig. 1) of patients with PTTN and healthy control subjects are presented. Resulting sensations on a numerical pain scale of 0 to 20 in response to 26g of force stimulation were recorded after the first and then at the end of every 10 stimuli out of a train of 30 successive stimuli. The stimuli were applied intraorally to the affected (injured) and contralateral sites and to the dominant forearm of the subjects. The data were recorded with and without conditioning pain stimulus (panel A) and presented in patients suffering from the condition for more or less than a year (panel B).

Figure 3

Responses to 2 g and…

Figure 3

Responses to 2 g and 26 g stimulation on a 0 to 20…

Figure 3
Responses to 2g and 26g stimulation on a 0 to 20 numerical pain scale were recorded from painful posttraumatic trigeminal neuropathy (PTTN) patients and healthy control subjects. Results show evaluations in the subjects' affected (injured) and contralateral intraoral sites and on the dominant forearm. Data are presented as mean ± SD. Nonparametric analysis was used to compare the difference between study groups. The exact Wilcoxon rank sum test was used to compare the medians of 2 groups (PTTN and control), and the exact Kruskal–Wallis test was used to compare the medians across multiple groups (PTTN > 1 year, PTTN < 1 year, and controls). (A) The arm response rating to 26g and 2g stimuli was significantly (*) elevated in the PTTN group compared with the control group. In the affected and contralateral sides, no significant differences were found between the PTTN and control groups. (B) Patients with PTTN for less than a year had a significantly (*) elevated response to 26g and 2g stimuli in the affected side compared with patients with PTTN who suffer from the condition for more than a year and controls. In the arm, patients with PTTN for less than a year had a significantly (*) elevated response to 26g and 2g stimuli compared with controls but not compared with patients with PTTN who suffer from the condition for more than a year.

Figure 4

Responses to cold application in…

Figure 4

Responses to cold application in patients with painful posttraumatic trigeminal neuropathy (PTTN) and…

Figure 4
Responses to cold application in patients with painful posttraumatic trigeminal neuropathy (PTTN) and healthy controls. Results show evaluations in the subjects' affected (injured) and contralateral trigeminal sites. Data are presented as mean ± SD. Nonparametric analysis was used to compare the difference between study groups. The exact Wilcoxon rank sum test was used to compare the medians of 2 groups (PTTN and control), and the exact Kruskal–Wallis test was used to compare the medians across multiple groups (PTTN > 1 year, PTTN
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    1. Baad-Hansen L. Atypical odontalgia—pathophysiology and clinical management. J Oral Rehabil 2008;35:1–11. - PubMed
    1. Baad-Hansen L, Juhl GI, Jensen TS, Brandsborg B, Svensson P. Differential effect of intravenous S-ketamine and fentanyl on atypical odontalgia and capsaicin-evoked pain. PAIN 2007;129:46–54. - PubMed
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Figure 2
Figure 2
The raw data used to calculate temporal summation and conditioned pain modulation (presented in Fig. 1) of patients with PTTN and healthy control subjects are presented. Resulting sensations on a numerical pain scale of 0 to 20 in response to 26g of force stimulation were recorded after the first and then at the end of every 10 stimuli out of a train of 30 successive stimuli. The stimuli were applied intraorally to the affected (injured) and contralateral sites and to the dominant forearm of the subjects. The data were recorded with and without conditioning pain stimulus (panel A) and presented in patients suffering from the condition for more or less than a year (panel B).
Figure 3
Figure 3
Responses to 2g and 26g stimulation on a 0 to 20 numerical pain scale were recorded from painful posttraumatic trigeminal neuropathy (PTTN) patients and healthy control subjects. Results show evaluations in the subjects' affected (injured) and contralateral intraoral sites and on the dominant forearm. Data are presented as mean ± SD. Nonparametric analysis was used to compare the difference between study groups. The exact Wilcoxon rank sum test was used to compare the medians of 2 groups (PTTN and control), and the exact Kruskal–Wallis test was used to compare the medians across multiple groups (PTTN > 1 year, PTTN < 1 year, and controls). (A) The arm response rating to 26g and 2g stimuli was significantly (*) elevated in the PTTN group compared with the control group. In the affected and contralateral sides, no significant differences were found between the PTTN and control groups. (B) Patients with PTTN for less than a year had a significantly (*) elevated response to 26g and 2g stimuli in the affected side compared with patients with PTTN who suffer from the condition for more than a year and controls. In the arm, patients with PTTN for less than a year had a significantly (*) elevated response to 26g and 2g stimuli compared with controls but not compared with patients with PTTN who suffer from the condition for more than a year.
Figure 4
Figure 4
Responses to cold application in patients with painful posttraumatic trigeminal neuropathy (PTTN) and healthy controls. Results show evaluations in the subjects' affected (injured) and contralateral trigeminal sites. Data are presented as mean ± SD. Nonparametric analysis was used to compare the difference between study groups. The exact Wilcoxon rank sum test was used to compare the medians of 2 groups (PTTN and control), and the exact Kruskal–Wallis test was used to compare the medians across multiple groups (PTTN > 1 year, PTTN

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