Genetic contributions to pain: a review of findings in humans

Pain represents the major motivating factor for which individuals seek healthcare, and pain responses are characterized by substantial inter‐individual differences. Increasing evidence suggests that genetic factors contribute significantly to individual differences in responses to both clinical and experimental pain. The purpose of this review article was to summarize the current literature regarding genetic contributions to pain, highlighting findings relevant to oral pain where available. A brief discussion of methodologic considerations is followed by a review of findings regarding genetic influences on clinical pain. Next, the literature examining genetic contributions to experimental pain responses is presented, emphasizing genetic associations that have been replicated in multiple cohorts. It is hoped that an enhanced understanding of genetic contributions to pain responses will ultimately improve diagnosis and treatment of clinical pain conditions.     

Chronic orofacial pain

The issues specific to trigeminal pain include the complexity of the region, the problematic impact on daily function and significant psychological impact (J Dent, 43 , 2015, 1203). By nature of the geography of the pain (affecting the face, eyes, scalp, nose, mouth), it may interfere with just about every social function we take for granted and enjoy (J Orofac Pain, 25 , 2011, 333). The trigeminal nerve is the largest sensory nerve in the body, protecting the essential organs that underpin our very existence (brain, eyes, nose, mouth). It is no wonder that pain within the trigeminal system in the face is often overwhelming and inescapable for the affected individual.     

Toothache with a multifactorial etiology: a case report

Abstract A case report of orofacial pain originating from both dental and nondental conditions is presented. The spontaneous throbbing pain initiated from the left maxillary second premolar and spread throughout the entire upper part of the lace to the frontoparietal area. Root canal treatment of the maxillary second premolar did not resolve the chief complaint. Magnetic resonance imaging examination revealed hypertrophy of the left inferior turbinate and soft tissue haziness in the left maxillary sinus floor. After antrostomy, submucosal turbinectomy; and endodontic treatment, the patient was free from pain. The final diagnosis of this case, in addition to pulpitis, was maxillary sinusitis with chronic rhinitis. The multiple factors associated with the etiology made the diagnosis difficult. The mechanism of referred pain from the maxillary sinus and paranasal nuicosa to the maxillary teeth and face is discussed.     

Relationship between specific temporomandibular disorders and impaired upper neck performance

Upper neck impairments are more prevalent in patients with temporomandibular disorders (TMDs) but the differences between specific types of TMDs are unclear. This study evaluated the distribution of such impairments among different forms of TMD. In total, 116 participants (86 women and 30 men, age range 21–75 yr) were investigated. Forty-two individuals had no TMDs and were assigned to the control group. The remaining 74 patients were assigned to one of three groups based on the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) findings: pain-related (n = 37); intra-articular (n = 17); or mixed (combined pain-related and intra-articular) (n = 20). Analyses of impairments included between-group comparisons of key parameters of upper neck performance (active/passive mobility and muscular capabilities) and pain (subjective neck disability and pain sensitivity). Patients in the pain-related and mixed TMD groups were found to have decreased upper neck mobility in the cervical flexion-rotation test compared with patients in intra-articular and control groups, as well as poorer capabilities of the deep neck flexor muscles in the cranio-cervical flexion test compared to the control group. It was concluded that patients with pain-related TMD diagnoses are more likely to experience significant upper-neck hypomobility and poor muscular capabilities than patients with intra-articular diagnoses of TMD.     

Clinical examination of patients with orofacial pain

Abstract A thorough clinical examination of patients with orofacial pain is of paramount importance. The examination is time-consuming, but is usually fully rewarding in that it may prevent unnecessary or incorrect and often irreversible treatment, and clarify to the clinician and hopefully to the patient the nature of the patient's problem. Only then may proper treatment be rendered. In this context it should be noted that a skillfully performed examination in these patients in itself provides valuable and effective treatment, especially when muscular dysfunction is the primary cause of the pain.     

Comparison of pain thresholds and pain tolerance levels between Middle Easterners and Swedes and between genders

Summary  Objective: This study evaluates the presence of culture and gender differences in pain thresholds and pain tolerance levels between Middle Easterners and Swedes. Methods: Sixty-four healthy individuals, 32 Middle Easterners (16 men and 16 women, mean age: 24·6 ± 3·4 years) and 32 Swedes (16 men and 16 women, mean age: 24 ± 3·5 years) participated in the study. Three experimental pain tests were conducted in each participant. Pain thresholds and pain tolerance levels were measured using an algometer (mechanical stimulus), the PainMatcher^® (electric stimulus) and cold pressor test (thermal stimulus). Results: While no significant differences in pain thresholds were observed between Middle Easterners and Swedes in algometer and cold pressor tests, differences in pain tolerance levels were significant ( P  < 0·01 for both tests). All between-culture differences in pain perception, pain threshold and pain tolerance level were non-significant when measured with the PainMatcher. Significant between-gender differences were observed only in pain threshold with the PainMatcher ( P  <   0·05) and in pain tolerance level with the algometer ( P  <   0·01) and the PainMatcher ( P  <0·001). Conclusion: This study found significant differences in two out of three pain tolerance level tests – but not pain threshold tests – between the Middle Eastern and Swedish cultures and between genders. These differences were more pronounced between Middle Eastern and Swedish men than between Middle Eastern and Swedish women. Gender differences were more pronounced within the Swedish than the Middle Eastern culture. These findings indicate that culture and gender influence pain experience.     

Orofacial pain assessment and management for patients with dementia: A meta‐ethnography

Delivering dental treatment for patients with dementia can be challenging, and the complexity of treatment provision can increase as dementia progresses. Treatment at the later stages of dementia can be associated with ethical challenges and procedural risk meaning that a comprehensive patient assessment is crucial; the presence of orofacial pain is a key indication for active intervention from dental teams. To explore the process of oro‐facial pain assessment and management, a comprehensive review of qualitative literature was undertaken by searching six electronic databases. No literature specific to orofacial pain assessment was identified. The inclusion criteria were widened to explore assessment and management of pain in general for patients with dementia. Meta‐ethnography with reciprocal translation was used to identify key concepts and themes and synthesise information applicable to the dental setting. Three major themes arose as follows: challenges with pain assessment, challenges with pain management and logistics and education. Healthcare teams struggle with pain identification in patients with dementia though many signs were identified which may suggest a patient is experiencing pain. The long‐term knowledge of individual patients held by family members and care teams can allow identification of deviation from patients’ normal states; this knowledge can assist healthcare professionals in determining whether to provide specific treatments or interventions. Pain assessment tools were found to be problematic and are unlikely to be a practical solution to use for complex patients in dental settings. Education for dental and wider care teams on orofacial pain would be highly valuable; yet, this needs to be based on suitable evidence.     

Influence of Preoperative Mechanical Allodynia on Predicting Postoperative Pain after Root Canal Treatment: A Prospective Clinical Study

IntroductionOdontogenic pain can manifest as pulpal pain, periapical pain (mechanical allodynia), or both. This study aimed to assess the changes in the intensity of mechanical allodynia (MA) and to identify predictors of postoperative pain after root canal treatment (RCT).MethodsIn total, 579 consecutive patients who required RCT were enrolled; we included patients with asymptomatic pulpal diagnoses to avoid any effects of preoperative spontaneous pain on postoperative pain and to evaluate MA independently. Using a visual analog scale (VAS), patients separately indicated the intensity of spontaneous pain, tenderness to percussion, and pain on biting; these measurements were performed before treatment (preoperative pain), at the beginning of each visit (postpreparation pain), and daily for 1 week after RCT (postobturation pain). For analytical purposes, patients were subdivided into 2 groups based on the intensity of preoperative MA (none to mild [VAS <4] or moderate to severe [VAS ≥4]) to evaluate changes in MA and predictive factors of moderate to severe postoperative pain. A generalized estimating equation, repeated-measures analysis of variance, and logistic regression analysis were used.ResultsAlthough the intensity of MA was significantly higher in the moderate to severe group after the initiation of RCT (P < .05), 93% of them experienced alleviation in MA, and 30% of patients in the none to mild group experienced an increase in MA. After adjusting for clinical variables, moderate to severe preoperative MA and the presence of necrotic pulp were significantly correlated with moderate to severe postoperative pain with an odds ratio of 4.107 and 0.286, respectively.ConclusionsModerate to severe preoperative MA was a predictive factor of postoperative pain in patients undergoing RCT.     

Referred Orofacial Pain as an Initial Symptom of Distant,Nonmetastatic Cancer: Report of a Case and Review of the Literature

Referred orofacial pain as the first symptom of an otherwise silent distant, nonmetastatic cancer has been reported, but there is sparse literature on the subject. Referred pain may not be considered in the orofacial pain differential diagnosis because of its rarity; however, this may delay a cancer diagnosis. The authors present a case report and a review of the English literature. Peer-reviewed publications were identified through a systematic search of MEDLINE, Embase, and Cochrane CENTRAL. Historic cases were reviewed, and available data regarding demographics, pain characteristics, treatment, cancer diagnosis, and outcome were extracted. Thirty-seven cases were identified. All cancers were intrathoracic. The average age was 54.1 years with a slight female predominance (3:2). Common pain characteristics were (1) diffuse location affecting the ear (76%), jaw (46%), and temple (30%); (2) constant duration (65%); (3) aching quality (74%); (4) severe intensity (94%); and (5) associated systemic symptoms (68%) such as weight loss and digital clubbing. The average time from the onset of facial pain to seeking medical attention was 9 months, and the average time from seeking medication attention to cancer diagnosis was 8 months. Orofacial pain was often attributed to odontogenic (35%) or neuropathic (25%) causes, and treatments for these conditions were also common. The impact of referred orofacial pain on the cancer prognosis was not possible because of the nature of the reviewed studies (case reports with no comparison group). Cancer-associated referred orofacial pain as a first symptom is rare but should be considered in cases with intractable pain and associated systemic symptoms.     

Factors associated with pain induced by orthodontic separators

Pain resulting from the application of orthodontic forces varies markedly across individuals. The reasons of this variability are still largely unknown. To investigate factors that may be associated with orthodontic pain following the application of orthodontic separators. One hundred and seven participants were screened for pain response over 48 h following placement of orthodontic elastomeric separators. The highest (n = 10) and lowest (n = 10) pain responders were identified, and data collected on tooth pain sensitivity to electrical stimulation in conjunction with using the Pain Catastrophising Scale (PCS), Dental Anxiety Scale (DAS) and cold pressor test (CPT). There were statistically significant differences between high‐ and low‐pain responders in catastrophising score (P ≤ 0·023). For every PCS magnification score of 1 unit higher, the relative risk of being a high‐pain responder was 1·6 (P = 0·002); those scoring higher on helplessness had a lower risk of being so. DAS scores of high‐pain responders were twice as high as those of low‐pain responder (P = 0·043). During the first 2 min of CPT, the high‐pain responders experienced more pain than the low‐pain responders (P ≤ 0·029). Tooth pain thresholds did not differ between the two different pain responder groups. Pain catastrophising, dental anxiety and cold sensitivity appear to modify the pain experienced following placement of orthodontic separators. Further research is needed to determine the validity of screening questions to identify at‐risk patients prior to commencing orthodontic treatment.     

The analgesic efficacy of ibuprofen in periodontal surgery: A multicentre study

The efficacy of a non-steroidal anti-inflammatory agent, ibuprofen, was evaluated in pain control following periodotal surgery. This type of agent acts peripherally by inhibiting the release of prostaglandins and minimizing the local inflammatory response. Thus there may be an advantage in pre-treatment administration of the drug so as to delay or even prevent postoperative pain.
The study was multicentre, involving a Public Hospital Periodontal Unit, two specialist periodontal practices in Sydney, NSW, ad two in Canberra, ACT. One hundred and twenty-seven pateints who were to undergo periodontal surgery were randomly given either two 200 mg tablets of ibuprofen or two matching placebo tablets at least 30 minutes before administration of local anaesthesia. The procedure was double blind: neither the patient nor the colinical was aware of the tablet identity.
Postoperatively, all patients were given labelled ibuprofen for pain relief, but were randomly divided into two groups: As directed who were instructed to take the drug regularly for two days postoperatively, and As required , who were to take the drug only if needed for pain relief. All patients completed a diary recording quantity and time of medication, and regular assessment of pain experience utilizing a viaual analogue scale.
The As directed group showed no significant difference in pain experience between pre-operative and post-operative only medication, but the As required group experienced significantly less pain and requirement for medication if the ibuprofen was administered pre-operatively.     

Self-reported severity of taste disturbances correlates with dysfunctional grade of TMD pain

Summary  Altered central neural processing of sensory information may be associated with temporomandibular disorders (TMD) pain. The objectives of this study were to compare the prevalence of self-reported taste disturbances in TMD pain patients and in a control population, and to determine whether frequency of taste disturbances was correlated with dysfunctional grade of TMD pain. Subjects were 2026 people within a German population sample and 301 consecutive TMD patients diagnosed using the Research Diagnostic Criteria. Taste disturbances were measured using two questions from the Oral Health Impact Profile. Dysfunctional grade of TMD pain was measured with the Graded Chronic Pain Scale. A two-sample test of proportions revealed that TMD patients reported a greater frequency of taste disturbances, 6%, than did the general population subjects, 2% ( P  < 0·001). Moreover, the frequency of taste disturbances correlated with the dysfunctional grade of TMD pain. For each 1 unit increase in taste disturbance, the odds of observing a higher grade of TMD pain increased by 29% (95% CI: 3–63%, P  = 0·03). Analysis by individual taste question and adjustment for age and gender did not substantially affect the results. These findings are consistent with a central neural dysfunction in TMD pain and suggest that a common neural substrate may underlie sensory disturbances of multiple modalities in chronic pain patients. Further research regarding taste disturbances and trigeminally mediated pains such as in TMD is warranted.     

Response Trends and Nonresponse Bias in a Mail Survey of Oral and Facial Pain

While mail surveys offer a low-cost method for collecting health data, they have been unpopular because of concerns about low response rates and nonresponse bias. This paper examines the response to a mail survey concerning oral and facial pain and uses regression techniques to assess the degree and direction of nonresponse bias on estimated prevalence rates. The analysis shows that early and late responders to the survey differed in terms of sociodemographic variables and responses to items concerning pain. The regression analysis suggests that the rather high prevalence rates revealed by the survey are not a product of bias induced by nonresponse and deserve further investigation.     

Chronic idiopathic orofacial pain. A long‐term follow‐up study

Patients suffering facial pain that does not fit with the traditional diagnostic criteria and which does not respond to dental treatment constitute a clinical problem. These patients lack a proper diagnosis and are frequently exposed to excessive and inadequate invasive treatment. The aim of this investigation was to study the long‐term development of pain and the result of treatment in a cohort of patients suffering chronic idiopathic facial pain. The 74 patients referred to the Facial Pain Diagnostic Group at the Karolinska Institute School of Dentistry between 1981 and 1992 were invited to take part in a follow‐up study. As 16 subjects were unwilling or unable to take part in the study and 13 had died, the remaining 45 were interviewed either in accordance with a standard protocol or by filling out a questionnaire mailed to them. The interview revealed that 10 were free of orofacial pain, but only 2 were totally free of pain. Over the 9–19 years' follow‐up period the relationship between facial pain and pain in the rest of the body had changed substantially. Of 14 patients and more than 100 extractions, permanent pain relief was felt by only 3 patients. It is concluded that a diagnosis was given in only 2 cases. The distribution of the pain has changed dramatically. The low success rate of invasive treatments suggests that such therapeutic methods are to be considered contraindicated in patients suffering from idiopathic orofacial pain.     

Orofacial pain – troll and control: five topics on clinical problems

Abstract Pain is etymologically combined with penalty, emotionally with anxiety and depression, and physiologically with inflammatory processes and other kinds of pressure augmentation in the tissues. Pain is a subjective experience that cannot be measured or “objectively” verified by other individuals. Reactions to pain, however, can be registered by others. Pain in the orofacial area may have several etiological explanations. Since the functional pattern of the area is multi-faceted, persisting pain in the area most likely has a multi-factorial background, and also a variety of effects. Treatment should be made considering delicate diagnostical distinctions. A thorough clinical examination contains lots of treatment components. This paper discusses some psychological factors in the diagnosis and treatment of orofacial pain.