**5. General considerations about clinical and epidemiological aspects of sleep-pain interaction**

Clinical evidence on sleep-general pain interaction comes essentially from insomnia patients. The severity of the insomnia is associated with pain sensitivity. In a recent study, we showed that prevalence of insomnia in orofacial pain patients was almost 40%; in more than 600 clinical patients, approximately 1 in 6 suffered from relevant insomnia corroborating this important relationship between pain and sleep disturbance [57]. In a review on comorbidities of chronic facial pain and obstructive sleep apnea, Olmos also stated that sleep disturbances may impact orofacial pain in a bidirectional way [58]. Patients with obstructive sleep apnea (OSA) or with other respiratory problems during sleep, one of the most common causes of disturbed and insufficient sleep, may actually present with more pain-related complaints and we have recently showed that in a large sample of patients with temporomandibular disorders and chronic orofacial pain 22% of patients presented with snoring which

is the most common sign of sleep apnea. Furthermore, when snoring and insomnia complaints are considered together, 6% of those patients presented with both symptoms increasing the likelihood of suffering from OSA [59]. The reasons for the higher prevalence of pain in patients with sleep disturbances were discussed previously in the pathophysiological section and could be related with either peripheral (e.g., release of proinflammatory cytokines and decrease in pain tolerance) or central mechanisms. Often medication, commonly prescribed for pain management, affects breathing during sleep and can even interfere with other common sleeprelated disturbances. For instance, mechanical management for pain control may affect normal respiration predisposing to sleep related breathing disorders [60].

Sleep impairment and chronic pain are also independently related with increased depressive symptoms. It has been speculated that pain, sleep, and depression could share some neurobiological matrix. Anxiety, mood changes, and depressive symptoms are however a common feature in the sleep disturbed patient, chronic pain patient, and patient with comorbidly sleep-pain-related complaints. Therefore, in patients with these complaints, it is important to adequately address these three main aspects: *Sleep*, *Pain*, and *Psychology*.
