In this study, we investigated whether impaired endogenous pain modulation could be part of the mechanisms underlying BMS in women. We found no changes in CPM efficiency in BMS patients, no changes in TSP, while neither thermal nor mechanical extracephalic pain thresholds were altered. However, the sensory profile of BMS patients was characterized by enhanced extracephalic heat hyperalgesia.
CPM is a powerful endogenous analgesic mechanism whereby a nociceptive stimulation applied to a given body location reduces the percept and brain responses elicited by noxious (test) stimuli delivered at a remote body location [6, 8]. Dysfunction of CPM is assumed to shift the balance between pain facilitation and inhibition toward facilitation and the development of chronic pain [6]. Here, we tested the hypothesis that abnormal CPM may be part of the pain mechanisms in BMS. However, in contrast to a previous study [10], this was not the case, since BMS patients were able to normally recruit their endogenous pain inhibitory system in our experimental setting. A similar hypothesis has been raised regarding the pathophysiology of other chronic orofacial pain conditions, but CPM has not always been reported to be impaired [13, 14] and appeared normal in some studies [7, 15, 16, 17] Such contradictory results – due in part to differences in methods used to assess CPM [6] - and the lack of aggregate analysis of the literature prevent any solid conclusion about the function of endogenous pain modulation in patients with chronic orofacial pain [7].
TSP, when assessed in response to repetitive laser-evoked thermal stimuli [11], was similar in BMS patients and control subjects. Similarly, a previous study, using intradermal electrical stimulation of the chin, found no difference in TPS between BMS and controls [10]. This is consistent with previous findings in other chronic orofacial pain syndromes, such as TMD, where TSP was normal when assessed with thermal stimuli [18, 19, 20, 21, 22]. In such patients though, TSP could be found altered [17, 23], when assessed with mechanical stimuli, as it sometimes increased [20]. Since thermal TSP relies, at least in part, on the activation of N-methyl-D-aspartate (NMDA) receptors, and thermal TSP is not altered in BMS patients, it seems likely that NMDA receptors do not play a critical role in the pathophysiology of BMS. Similar mechanistic suggestions have been made about patients suffering from persistent post-endodontic pain [14].
Despite normal TSP, BMS patients showed greater extracephalic heat hyperalgesia than control subjects. An enhanced heat hyperalgesia seems common in patients with chronic, either cephalic [20, 21] or extracephalic [24], pain. In all these conditions, the presence of hyperalgesia suggests a facilitation of pain mechanisms in BMS patients. In addition, hyperalgesia has been shown to be predictive of poor outcomes in some chronic pain conditions [25], and this may also apply to BMS.
Although we cannot exclude the possibility that the enhanced heat hyperalgesia in BMS patients results from peripheral mechanisms, several observations rather suggest a central contribution. Indeed, neither heat pain thresholds nor MPTs were reduced in the BMS group, showing that thermal and mechanical nociceptors were not sensitized. Since CPM efficiency was similar in BMS patients and controls subjects, a reduction in CPM cannot explain the enhanced heat hyperalgesia that may rather relies on increased pain facilitating mechanisms.
Limitations
We are aware of the limitations that apply to the present study. First, our sample was limited to females and our results thus cannot be generalized to males. Second, we studied a peri-menopausal population in which CPM effect is known to weaken with age. Third, although the sample size was selected based on a previous study [12], the methodology in the present study did not exactly match that in the previous one, and consequently, the sample size might have been underestimated to detect between-group differences. Finally, we did not look for possible differences between body regions [26].