REVIEW For reprint orders, please contact: [email protected]
Widespread pain in temporomandibular disorders
Practice Points
Pei Feng Lim†1, William Maixner1 & Asma A Khan1 It is important to recognize that many chronic pain conditions are comorbid and, therefore, result in a
state of chronic widespread pain in many patients. Temporomandibular disorders is one of the most extensively studied chronic pain conditions in terms of
its comorbidity with chronic widespread pain and fibromyalgia. These comorbid conditions share several common features including increased pain sensitivity, fatigue
and sleep difficulties. Failure to effectively diagnose and manage comorbid pain conditions will negatively impact the
treatment response. In the out-patient setting, self-administered questionnaires and quantitative sensory testing can aid in
the diagnosis of chronic widespread pain. Patients with chronic widespread pain can be effectively managed in multidisciplinary pain clinics.
SUMMARY
Chronic widespread pain (CWP) represents pain involving several regions of the body. Various psychological and social risk factors such as poor general health status, sleep disturbance, fatigue and high psychological distress have been identified for the development of CWP. Numerous chronic pain conditions are comorbid, resulting in the development of CWP in many of these patients. Temporomandibular disorder is one of the most extensively studied chronic musculoskeletal pain condition in terms of its comorbidity with CWP and fibromyalgia. It has been proposed that these comorbid pain disorders share common denominators, including exposure to certain environmental events, elevated psychological distress, pain amplification and genetic predisposition. Increased awareness of CWP is important for improved diagnoses and more effective pain management. Patients with CWP can be effectively managed in multidisciplinary pain clinics. Three distinct patterns of pain distribution, namely localized, regional and widespread pain, are generally recognized [1,2] . Chronic widespread pain (CWP) represents pain
involving several regions of the body [3] . The point prevalence of CWP in the general pop ulation is estimated to be 11.2% [4] . Various psychological and social risk factors have been
Center for Neurosensory Disorders, University of North Carolina at Chapel Hill, 2054 Old Dental Building, CB 7455, Chapel Hill, NC 27599, USA † Author for correspondence: Tel.: +1 919 966 0684; Fax: +1 919 966 3683; [email protected] 1
10.2217/PMT.11.3 © 2011 Future Medicine Ltd
Pain Manage. (2011) 1(2), 181–187
ISSN 1758-1869
181
Review Lim, Maixner & Khan identified as risk factors for the future develop ment of CWP. These include poor general health status, sleep disturbance, fatigue and high psychological distress [5] . A small pro portion of individuals with CWP reportedly have multiple symptoms since childhood [6] , and children with behavioral problems or other somatic symptoms may be at increased risk [7] . Both increased and decreased mortality have been reported in people with CWP [8,9] . The predictors of the development of CWP include the number of painful regions at baseline [10] , and psychosocial factors such as somatiza tion [11] , health-seeking behavior and poor sleep [12] . However, the most important clini cal risk factor for chronic pain at a specific site appears to be pain in itself [13] . Von Korff et al. reported that the presence of a pain condition at baseline was a more consistent predictor of subsequent risks of developing a new pain con dition than the severity or chronicity of depres sive symptoms [14] . Therefore, chronic pain is rarely present at a single body site [15] . Complex persistent pain conditions (CPPCs) [9] , also known as functional pain syndromes, share similarities in terms of clini cal pain complaints [16] . These comorbid con ditions include, but are not limited to, fibro myalgia (FM), irritable bowel syndrome (IBS), temporomandibular disorders (TMD), vulvar vestibulitis (formerly known as vulvodynia), chronic headache, interstitial cystitis and chronic tinnitus. Irrespective of the peripheral pain location, CPPCs are probably regulated in a similar fashion [17] . Diatchenko et al. pro posed that these idiopathic pain disorders share common denominators [18] , including exposure to certain environmental events [19] , elevated psychological distress [20] , pain amplification [21] and genetic predisposition [22] . These pathways of vulnerability are interactive and influence the risk of pain onset and persistence. In the light of current scientific knowledge, what were once ‘medically unexplained symptoms’ and ‘functional somatic syndromes’ have become ‘CPPCs’ and ‘central sensitivity syndromes’ [23] . CWP is a cardinal feature of CPPCs. Temporomandibular disorder is a musculo skeletal pain condition affecting the temporo mandibular joints, masticatory muscles and/or associated structures [24] . It is one of the most extensively studied CPPCs with respect to comorbidity, pain mechanisms and risk fac tors [9] . In the next section, we will elaborate on
182
Pain Manage. (2011) 1(2)
the comorbidity of TMD with CWP and FM to illustrate the link between pain in a localized bodily area and widespread body pain. TMD & CWP Various studies have reported that facial pain is comorbid with widespread bodily pain [2] , including FM [25] , vulvar vestibulitis [26] and lower back pain [27] . The presence of pain out side the masticatory system is a known risk fac tor for the development of TMD [14] . A prospec tive study reported that, after adjusting for age, gender, education and depression severity, peo ple with a pain condition at baseline were more likely to report the onset of TMD pain over a 3‑year follow-up period compared with those without a pain condition at baseline (adjusted odds ratios of 3.7) [14] . Another study demon strated that subjects who developed TMD more frequently reported experience of joint, back, chest and menstrual pain at baseline and at the onset of TMD as compared with those subjects who did not develop this disorder [28] . Over a 2‑year period, signs of TMD at baseline pre dicted the onset of spinal pain, and spinal pain at baseline predicted the onset of TMD [29] . In addition, Korszun et al. found that 67% of their cohort of TMD subjects reported an onset of generalized pain symptoms before the onset of facial pain [20] . Macfarlane et al. found that pain in parts of the body other than the head lead to a threefold increase in the risk of develop ing TMD [19] . Studies evaluating the relation ship between TMD and its comorbidities have also identified a correlation between the fre quency/severity of the comorbidity and TMD. Wiesinger et al. reported that the prevalence of TMD symptoms and headaches increased with an increase in the frequency or severity of spinal pain and vice versa [30] . These findings suggest that it would be inappropriate to con sider TMD in isolation; instead, regional and widespread chronic pain conditions represent ‘overlapping’ conditions and should be consid ered as part of a ‘continuum’ rather than dis tinct entities with distinct etiologies [1] . In fact, the presence of one pain condition at baseline has been demonstrated to be associated with a fourfold increased risk of developing TMD [14] , and one of the strongest predictors for the onset of chronic TMD was CWP [31] . Raphael et al. reported that the occurrence of TMD with widespread body pain may impact the manage ment of such patients, because patients with
future science group
Widespread pain in temporomandibular disorders CWP are more likely to have more persistent and debilitating facial pain than those with no history of widespread pain [32] . TMD & FM While the diagnosis of FM is commonly based on the American College of Rheumatology cri teria of widespread pain and tenderness in at least 11 out of 18 musculoskeletal sites (tender points) for at least 3 months [33] , it has been effectively argued that tender points are merely markers of distress and severity and that FM represents one end of the widespread chronic pain continuum [34] . This led to the recently revised and simplified American College of Rheumatology criteria for the diagnosis of FM, which are based on the presence of widespread pain and symptoms for at least 3 months [35] . While FM has been defined as a form of CWP with widespread allodynia to pressure pain [36] , the relationship between these two entities is not completely clear [1] . Many view FM as a clinically distinct syndrome; although current literature suggest that FM is at the severe end of the CWP spectrum. Studies evaluating the overlap between FM and TMD report that 35.4–97.0% of FM patients have signs and symptoms of TMD [37] , while the prevalence of FM in TMD patients was an estimated 52% [38] . Similarities reported in both conditions included comparable clinical pain reports [39] , common symptoms, such as sleep difficulty and fatigue [21] , and psychopathology, such as depression and anxiety disorder [21,40] , again suggesting that TMD pain in FM patients may be an extension of the CWP rather than a separate entity. CWP: underlying mechanisms Several lines of evidence indicate that altera tions in central pain signaling play an impor tant role in the onset and/or exacerbation of CWP [41] . Temporal summation and diffuse noxious inhibitory control (DNIC) are com monly used to investigate central nociceptive processing in chronic pain patients. Temporal summation refers to enhanced pain intensity in response to repetitive noxious stimulation [42] . Patients with FM demonstrate abnormal tempo ral summation [43] and, for TMD patients, this enhanced temporal summation is not usually limited to the area of clinical pain [44] . This led Wolfe et al. to suggest that jaw pain may be a marker for general pain increase and symptom
future science group
Review
sensitivity [37] . DNIC refers to a phenomenon of counter-irritation whereby pain perception from one nociceptive stimulus is significantly inhibited by a second nociceptive stimulus administered at a distant site. In a recent study comparing DNIC in patients diagnosed with IBS or TMD with healthy controls, a painful conditioning stimulus (foot immersion in a noxious cold water bath) was used to moder ate pain elicited by a focal thermal stimulus to the hand [45] . Unlike the healthy controls, patients with TMD or IBS did not experience a significant decrease in pain intensity. Reduced DNIC [46] and enhanced temporal summation [47] have also been demonstrated in patients with FM and chronic headaches. Taken together, these studies suggest generalized hyperexcitabil ity of the central nociceptive system in patients with CPPCs. In addition, centrally acting medi cations, such as antidepressants, exert an anal gesic effect independent of their antidepressant effect in chronic pain patients [48] , providing further evidence supporting dysfunctions in central nociceptive processing in CPPCs [49] . Alterations in the sympathetic nervous sys tem function have also been observed in patients with TMD, FM and IBS [50] . These alterations include increased sympathetic nervous system drive at rest and an attenuated sympathetic ner vous system-mediated response to challenges, such as postural changes and exercise [50] . Several studies have demonstrated that patients with FM and TMD have lower levels of nor epinephrine at rest and have a deficient norepi nephrine response to stress as compared with pain-free controls [51] . A recent double-blind, crossover, placebo-controlled trial reported that proponalol, a b‑adrenergic antagonist, reduced the total number of painful sites and pain rating in patients with TMD and FM [52] . Pregabalin, an anticonvulsant drug that reduces the synaptic release of neurotransmitters, such as norepineph rine, glutamate and substance P, had a signifi cant analgesic effect in FM and IBS patients [53] . These studies, among others, provide substantial evidence that abnormalities in the function of the hypothalamic–pituitary–adrenal axis is one of the hallmarks of CPPC [54] . Recently, reduc tion in levels of anti-inflammatory cytokines was reported in patients with CWP [55] . Human genetic studies have revealed associa tions between genetic polymorphisms and the development of chronic pain syndromes [22,56,57] . Genetic variants are known to influence the
www.futuremedicine.com
183
Review Lim, Maixner & Khan expression and function of local mediators as well as nociceptive signaling pathways, neuro plasticity and mechanisms influencing mood [58,59,60] . It has been proposed that common functional polymorphisms in genes known to influence the processing and perception of pain represent areas of genetic vulnerability that, when coupled to environmental triggers, con tribute to enhanced pain perception, psychologi cal dysfunction, risk of onset and persistence of TMD, and related idiopathic pain disorders [22] . Three genetic variants of the gene encoding cat echolamine-O-methyltransferase designated as low, average and high pain sensitivity haplotypes were recently identified [22] . The presence of even a single low pain sensitivity haplotype reduces the risk of developing TMD by 2.3‑fold. Future prospective studies are required to investigate the genetic vulnerability, and shared physical, psychological and social risk factors associated with the onset and maintenance of CWP. Clinical implications In a recent editorial published in Pain, Croft et al. cautioned readers that “anyone setting out to study a particular association between two pain syndromes can be both reassured (you will find it) and cautioned (there will be nothing spe cial about the result)” [61] . As discussed earlier, these comorbid conditions share several com mon features, including increased pain sensitiv ity, fatigue and sleep difficulties, which often result in missed diagnosis. Patients presenting with ‘unexplained’ syndromes are often treated symptomatically while coexisting comorbidi ties are ignored, thereby resulting in failure of treatment and perpetuation of the problem [62] . This probably explains the increased number of consultations for musculoskeletal and nonmusculoskeletal problems in people with CWP than in those with no pain, for example [63] . Restorative sleep has been demonstrated to pre dict the resolution of CWP [64] . Focusing on reducing pain symptoms in a particular body region without attention to comorbid condi tions, such as poor sleep quality, will invariably result in treatment failure. Therefore, increased awareness of the overlap between the various CPPCs is important for improved diagnoses and more effective pain management. Various simple self-administered question naires are available to aid in the assessment of possible comorbid pain conditions. An example is the Fibromyalgia Rapid Screening
184
Pain Manage. (2011) 1(2)
Tool (FiRST), which is a six-item inventory requiring ‘yes’/‘no’ responses with a sensitivity of 90.5% and a specificity of 85.7% in the detec tion of FM [65] . The ID Migraine™ screener is a three-item questionnaire requiring ‘yes’/‘no’ responses with a positive predictive value of 93% [66] . Assessment of associated symptoms such as depression and anxiety [67] , somatiza tion [68] , insomnia [69] , and fatigue [70] can also be assessed by various validated short question naires. Novel ‘markers’ of CWP include quanti tative sensory testing measures, such as assess ment of the pressure pain threshold, tender point counts [71] , thermal pain perception [72] and temporal summation [43] . Patients with CWP can be very satisfacto rily managed at a multidisciplinary pain clinic. Interdisciplinary consultations, which have become the rule rather than the exception, are invaluable owing to the complex nature of the biopsychosocial factors underlying CWP. Therefore, it is not surprising that a chronic pain patient may perhaps receive management simultaneously from a psychologist, an anes thesiologist, a physical therapist, a neurologist and a dental (orofacial) pain specialist. Various psychological interventions, such as cognitive behavioral therapy, have been repeatedly docu mented to be efficacious in the management of CWP [73] . Pharmacotherapeutics, rehabilita tion medicine and various regional analgesic techniques or procedures are often pursued a longside standard care. Pharmacotherapy for CWP often includes a combination of various analgesics with dif ferent mechanisms of action, complementary pharmacokinetics and multiple sites of action along the pain pathway. This results in a syner gistic analgesic effect along with a (hopefully) reduced adverse event profile [74] . Examples of commonly used pain medications include antidepressants, anticonvulsants and simple analgesics [75] . Recent investigations reported good efficacy of duloxetine and milnacip rain in CWP [76–78] . Other promising agents include sodium oxybate, dopamine agonists, synthetic cannabinoids and NMDA antago nists. A recent randomized controlled clinical trial investigating the pharmacogenetic effect of catecholamine-O-methyltransferase on treatment response to propranolol in patients with chronic musculoskeletal pain found that catecholamine-O-methyltransferase haplotypes may serve as genetic predictors of treatment
future science group
Widespread pain in temporomandibular disorders outcome, identifying the subgroup of patients who will or will not benefit from propranolol therapy [79] . Future studies need to address the impact of genetic modulation on the effects of analgesics used in chronic pain management [80] . In one study, baseline erythrocyte sedimen tation rate reportedly predicted over 80% of the variance in response to low-dose naltrexone in FM, indicating the possible usefulness of this test in identifying a subgroup of FM patients responsive to this therapy [81] . Another chal lenging area lies in the management of postop erative pain in patients with CWP due to the increased risk of postoperative acute and pro longed pain. Multimodal approaches that have been recommended include the use of phar macotherapeutics targeted at reducing central sensitization, regional analgesia techniques and psychological supportive measures [82] . Conclusion & future perspective Chronic widespread pain is a feature of CPPCs (i.e., TMD, IBS and FM), which are comorbid pain disorders that share numerous common pathways of vulnerability, including pain Bibliography
7
Papers of special note have been highlighted as: of interest of considerable interest n
amplification, elevated psychological distress and genetic predisposition. Failure to recognize these comorbid idiopathic pain disorders will negatively impact diagnosis and, thus, the treat ment response. Various validated self-admin istered questionnaires can assist in the ‘detec tion’ of the presence of such comorbidities. The m anagement of patients with CWP is best carried out at a multidisciplinary pain clinic. Future perspective studies are needed to investigate the genetic vulnerability, and shared physical, psychological and social risk factors associated with the onset and maintenance of CWP. Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.
Jones GT, Silman AJ, Macfarlane GJ: Predicting the onset of widespread body pain among children. Arthritis Rheum. 48, 2615–2621 (2003).
12 Gupta A, Silman AJ, Ray D et al.: The role of
psychosocial factors in predicting the onset of chronic widespread pain: results from a prospective population-based study. Rheumatology (Oxford) 46, 666–671 (2007).
n n
1
2
3
4
Macfarlane GJ: Generalized pain, fibromyalgia and regional pain: an epidemiological view. Baillieres Best Pract. Res. Clin. Rheumatol. 13, 403–414 (1999). Turp JC, Kowalski CJ, O’Leary N, Stohler CS: Pain maps from facial pain patients indicate a broad pain geography. J. Dent. Res. 77, 1465–1472 (1998). Cieza A, Stucki G, Weigl M et al.: ICF core sets for chronic widespread pain. J. Rehabil. Med. 63–68 (2004). Croft P, Rigby AS, Boswell R, Schollum J, Silman A: The prevalence of chronic widespread pain in the general population. J. Rheumatol. 20, 710–713 (1993).
5
Bergman S: Psychosocial aspects of chronic widespread pain and fibromyalgia. Disabil. Rehabil. 27, 675–683 (2005).
6
Jones GT, Silman AJ, Power C, Macfarlane GJ: Are common symptoms in childhood associated with chronic widespread body pain in adulthood? Results from the 1958 British Birth Cohort Study. Arthritis Rheum. 56, 1669–1675 (2007).
future science group
8
9
n n
10
11
Review
Macfarlane GJ, McBeth J, Silman AJ: Widespread body pain and mortality: prospective population based study. BMJ 323, 662–665 (2001). Maixner W: Temporomandibular joint disorders. In: Functional Pain Syndromes: Presentation and Pathophysiology. Mayer EA, Bushnell MC (Eds). IASP Press, Seattle, WA, USA (2009).
13 Smith BH, Macfarlane GJ, Torrance N:
Epidemiology of chronic pain, from the laboratory to the bus stop: time to add understanding of biological mechanisms to the study of risk factors in population-based research? Pain 127, 5–10 (2007). 14
Highlights temporomandibular disorder as a complex persistent pain condition. A summary of current research on the pathophysiology of temporomandibular disorders is presented.
Von Korff M, LeResche L, Dworkin S: First onset of common pain symptoms: a prospective study of depression as a risk factor. Pain 55, 251–258 (1993).
15
Bergman S, Herrstrom P, Jacobsson LT, Petersson IF: Chronic widespread pain: a three year followup of pain distribution and risk factors. J. Rheumatol. 29, 818–825 (2002).
Carnes D, Parsons S, Ashby D et al.: Chronic musculoskeletal pain rarely presents in a single body site: results from a UK population study. Rheumatology (Oxford) 46, 1168–1170 (2007).
16
Von Korff M, Dworkin SF, Le Resche L, Kruger A: An epidemiologic comparison of pain complaints. Pain 32, 173–183 (1988).
17
Grossi ML, Goldberg MB, Locker D, Tenenbaum HC: Irritable bowel syndrome patients versus responding and nonresponding temporomandibular disorder patients: a neuropsychologic profile comparative study. Int. J. Prosthodont. 21, 201–209 (2008).
McBeth J, Macfarlane GJ, Benjamin S, Silman AJ: Features of somatization predict the onset of chronic widespread pain: results of a large population-based study. Arthritis Rheum. 44, 940–946 (2001).
www.futuremedicine.com
185
Review Lim, Maixner & Khan 18
n n
19
Diatchenko L, Nackley AG, Slade GD, Fillingim RB, Maixner W: Idiopathic pain disorders – pathways of vulnerability. Pain 123, 226–230 (2006). Review of idiopathic pain disorders that presents a proposed model for pathways of vulnerability for the development of chronic pain. Macfarlane TV, Gray RJM, Kincey J, Worthington HV: Factors associated with the temporomandibular disorder, pain dysfunction syndrome (PDS): Manchester case-control study. Oral Dis. 7, 321–330 (2001).
20 Korszun A, Papadopoulos E, Demitrack M,
21
28 Lim PF, Smith S, Bhalang K, Slade GD,
Maixner W: Development of temporomandibular disorders is associated with greater bodily pain experience. Clin. J. Pain 26, 116–120 (2010). Reciprocal influence on the incidence of symptoms in trigeminally and spinally innervated areas. Eur. J. Pain 14, 366–371 (2010). Wanman A: Does a dose–response relation exist between spinal pain and temporomandibular disorders? BMC Musculoskelet. Disord. 10, 28 (2009).
32 Raphael KG, Marbach JJ, Klausner J:
Myofascial face pain. Clinical characteristics of those with regional vs. widespread pain. J. Am. Dent. Assoc. 131, 161–171 (2000). American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum. 33, 160–172 (1990).
Genetic basis for individual variations in pain perception and the development of a chronic pain condition. Hum. Mol. Genet. 14, 135–143 (2005).
34 Wolfe F: The relation between tender points
and fibromyalgia symptom variables: evidence that fibromyalgia is not a discrete disorder in the clinic. Ann. Rheum. Dis. 56, 268–271 (1997).
a new paradigm and group nosology for fibromyalgia and overlapping conditions, and the related issue of disease versus illness. Semin. Arthritis Rheum. 37, 339–352 (2008).
25 Balasubramaniam R, de Leeuw R, Zhu H,
Nickerson RB, Okeson JP, Carlson CR: Prevalence of temporomandibular disorders in fibromyalgia and failed back syndrome patients: a blinded prospective comparison study. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 104, 204–216 (2007). 26 Zolnoun DA, Rohl J, Moore CG,
Perinetti-Liebert C, Lamvu GM, Maixner W: Overlap between orofacial pain and vulvar vestibulitis syndrome. Clin. J. Pain 24, 187–191 (2008). 27 Wiesinger B, Malker H, Englund E,
Wanman A: Back pain in relation to musculoskeletal disorders in the jaw-face: a matched case-control study. Pain 131, 311–319 (2007).
Major psychological disorders in acute and chronic TMD: an initial examination. J. Am. Dent. Assoc. 127, 1365–1370 (1996). 41 Vierck CJ Jr: Mechanisms underlying
development of spatially distributed chronic pain (fibromyalgia). Pain 124, 242–263 (2006). 42 Vierck CJ Jr, Cannon RL, Fry G, Maixner W,
Whitsel BL: Characteristics of temporal summation of second pain sensations elicited by brief contact of glabrous skin by a preheated thermode. J. Neurophysiol. 78, 992–1002 (1997). 43 Staud R, Robinson ME, Price DD: Temporal
summation of second pain and its maintenance are useful for characterizing widespread central sensitization of fibromyalgia patients. J. Pain 8, 893–901 (2007). 44 Sarlani E, Greenspan JD: Why look in the
33 Wolfe F, Smythe HA, Yunus MB et al.: The
22 Diatchenko L, Slade GD, Nackley AG et al.:
186
Aggarwal VR, Macfarlane GJ, Farragher TM, McBeth J: Risk factors for onset of chronic oro-facial pain – results of the North Cheshire oro-facial pain prospective population study. Pain 149, 354–359 (2010).
Aaron LA, Burke MM, Buchwald D: Overlapping conditions among patients with chronic fatigue syndrome, fibromyalgia, and temporomandibular disorder. Arch. Intern. Med. 160, 221–227 (2000).
Orofacial Pain. Guidelines for Assessment, Diagnosis, and Management. de Leeuw R (Ed.). Quintessence Publishing Co. Inc., Hanover Park, IL, USA (2008).
40 Gatchel RJ, Garofalo JP, Ellis E, Holt C:
30 Wiesinger B, Malker H, Englund E,
31
24 The American Academy of Orofacial Pain:
The incidence of pain in the muscles of mastication in patients with fibromyalgia. J. Mass Dent. Soc. 47, 8–12 (1998).
29 Marklund S, Wiesinger B, Wanman A:
Engleberg C, Crofford L: The relationship between temporomandibular disorders and stress-associated syndromes. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 86, 416–420 (1998).
23 Yunus MB: Central sensitivity syndromes:
39 Pennacchio EA, Borg-Stein J, Keith DA:
35
Wolfe F, Clauw DJ, Fitzcharles MA et al.: The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res. (Hoboken) 62, 600–610 (2010).
36 Coster L, Kendall S, Gerdle B, Henriksson C,
Henriksson KG, Bengtsson A: Chronic widespread musculoskeletal pain – a comparison of those who meet criteria for fibromyalgia and those who do not. Eur. J. Pain 12, 600–610 (2008). 37 Wolfe F, Katz RS, Michaud K: Jaw pain: its
prevalence and meaning in patients with rheumatoid arthritis, osteoarthritis, and fibromyalgia. J. Rheumatol. 32, 2421–2428 (2005) 38 Leblebici B, Pektas ZO, Ortancil O,
Hurcan EC, Bagis S, Akman MN: Coexistence of fibromyalgia, temporomandibular disorder, and masticatory myofascial pain syndromes. Rheumatol. Int. 27, 541–544 (2007).
Pain Manage. (2011) 1(2)
brain for answers to temporomandibular disorder pain? Cells Tissues Organs 180, 69–75 (2005). 45
King CD, Wong F, Currie T, Mauderli AP, Fillingim RB, Riley JL 3rd: Deficiency in endogenous modulation of prolonged heat pain in patients with irritable bowel syndrome and temporomandibular disorder. Pain 143, 172–178 (2009).
46 de Souza JB, Potvin S, Goffaux P, Charest J,
Marchand S: The deficit of pain inhibition in fibromyalgia is more pronounced in patients with comorbid depressive symptoms. Clin. J. Pain 25, 123–127 (2009). 47 Desmeules JA, Cedraschi C, Rapiti E et al.:
Neurophysiologic evidence for a central sensitization in patients with fibromyalgia. Arthritis Rheum. 48, 1420–1429 (2003). 48 Perrot S, Javier RM, Marty M, Le Jeunne C,
Laroche F: Is there any evidence to support the use of anti-depressants in painful rheumatological conditions? Systematic review of pharmacological and clinical studies. Rheumatology (Oxford) 47, 1117–1123 (2008). 49 McQuay HJ, Carroll D, Glynn CJ:
Dose-response for analgesic effect of amitriptyline in chronic pain. Anaesthesia 48, 281–285 (1993). 50 Giske L, Vollestad NK, Mengshoel AM,
Jensen J, Knardahl S, Roe C: Attenuated adrenergic responses to exercise in women with fibromyalgia – a controlled study. Eur. J. Pain 12, 351–360 (2008).
future science group
Widespread pain in temporomandibular disorders 51
Martinez-Lavin M: Biology and therapy of fibromyalgia. Stress, the stress response system, and fibromyalgia. Arthritis Res. Ther. 9(4), 216 (2007).
52
Light KC, Bragdon EE, Grewen KM, Brownley KA, Girdler SS, Maixner W: Adrenergic dysregulation and pain with and without acute b‑blockade in women with fibromyalgia and temporomandibular disorder. J. Pain 10, 542–552 (2009).
unexplained: do they have common associated factors? Int. J. Epidemiol. 35, 468–476 (2006). 63 Kadam UT, Thomas E, Croft PR: Is chronic
widespread pain a predictor of all-cause morbidity? A 3 year prospective population based study in family practice. J. Rheumatol. 32, 1341–1348 (2005).
54 McBeth J, Chiu YH, Silman AJ et al.:
55
66 Lipton RB, Dodick D, Sadovsky R et al.:
Uceyler N, Valenza R, Stock M, Schedel R, Sprotte G, Sommer C: Reduced levels of antiinflammatory cytokines in patients with chronic widespread pain. Arthritis Rheum. 54, 2656–2664 (2006).
67 Lowe B, Wahl I, Rose M et al.: A 4-item
Three major haplotypes of the b2 adrenergic receptor define psychological profile, blood pressure, and the risk for development of a common musculoskeletal pain disorder. Am. J. Med. Genet. B Neuropsychiatr. Genet. 141B(5), 449–462 (2006). 57 Hocking LJ, Smith BH, Jones GT, Reid DM,
Strachan DP, Macfarlane GJ: Genetic variation in the b2-adrenergic receptor but not catecholamine-O-methyltransferase predisposes to chronic pain: results from the 1958 British Birth Cohort Study. Pain 149(1), 143–151 (2010), Erratum in 150(1), 210 (2010). 58 Diatchenko L, Nackley AG, Tchivileva IE,
Shabalina SA, Maixner W: Genetic architecture of human pain perception. Trends Genet. 23(12), 605–613 (2007). 59 Foulkes T, Wood JN: Pain genes. PLoS Genet.
4(7), e1000086 (2008). 60 Tremblay J, Hamet P: Genetics of pain,
opioids, and opioid responsiveness. Metabolism 59(Suppl. 1). S5–S8 (2010). 61
Perrot S, Bouhassira D, Fermanian J: Development and validation of the Fibromyalgia Rapid Screening Tool (FiRST). Pain 150, 250–256 (2010).
Croft P, Dunn KM, Von Korff M: Chronic pain syndromes: you can’t have one without another. Pain 131, 237–238 (2007).
62 Aggarwal VR, McBeth J, Zakrzewska JM,
Lunt M, Macfarlane GJ: The epidemiology of chronic syndromes that are frequently
future science group
Ozaki N, Kurita K: Effectiveness of milnacipran for the treatment of chronic pain in the orofacial region. Clin. Neuropharmacol. 33, 79–83 (2010). 77 Kyle JA, Dugan BD, Testerman KK:
Milnacipran for treatment of fibromyalgia. Ann Pharmacother. 44, 1422–1429 (2010). 78 Wright CL, Mist SD, Ross RL, Jones KD:
Duloxetine for the treatment of fibromyalgia. Expert Rev. Clin. Immunol. 6, 745–756 (2010).
68 Kroenke K, Spitzer RL, Williams JB:
The PHQ‑15: validity of a new measure for evaluating the severity of somatic symptoms. Psychosom. Med. 64, 258–266 (2002).
79 Tchivileva IE, Lim PF, Smith SB et al.:
Effect of catechol-O-methyltransferase polymorphism on response to propranolol therapy in chronic musculoskeletal pain: a randomized, double-blind, placebocontrolled, crossover pilot study. Pharmacogenet. Genomics 20, 239–248 (2010).
69 Violani C, Devoto A, Lucidi F, Lombardo C,
Russo PM: Validity of a short insomnia questionnaire: the SDQ. Brain Res. Bull. 63, 415–421 (2004). 70 Hadzi-Pavlovic D, Hickie IB, Wilson AJ,
Davenport TA, Lloyd AR, Wakefield D: Screening for prolonged fatigue syndromes: validation of the SOFA scale. Soc. Psychiatry Psychiatr. Epidemiol. 35, 471–479 (2000). 71 Gupta A, McBeth J, Macfarlane GJ et al.:
Pressure pain thresholds and tender point counts as predictors of new chronic widespread pain in somatising subjects. Ann. Rheum. Dis. 66, 517–521 (2007).
80 Lotsch J, Geisslinger G, Tegeder I:
Genetic modulation of the pharmacological treatment of pain. Pharmacol. Ther. 124, 168–184 (2009). n n
81
72 Fernandez-de-las-Penas C, Galan-del-Rio F,
Ortega-Santiago R, Jimenez-Garcia R, Arendt-Nielsen L, Svensson P: Bilateral thermal hyperalgesia in trigeminal and extra-trigeminal regions in patients with myofascial temporomandibular disorders. Exp. Brain Res. 202, 171–179 (2010). 73 Kroner-Herwig B: Chronic pain syndromes
and their treatment by psychological interventions. Curr. Opin. Psychiatry 22, 200–204 (2009).
Presents a summary of meta-analyses and systematic reviews published since 2005 examining pharmacotherapy for chronic pain management.
76 Ito M, Kimura H, Yoshida K, Kimura Y,
A self-administered screener for migraine in primary care: the ID Migraine validation study. Neurology 61, 375–382 (2003). measure of depression and anxiety: validation and standardization of the Patient Health Questionnaire-4 (PHQ-4) in the general population. J. Affect Disord. 122, 86–95 (2010).
Raffa RB: Pharmacology of oral combination analgesics: rational therapy for pain. J. Clin. Pharm. Ther. 26, 257–264 (2001). Pharmacotherapy of chronic pain: a synthesis of recommendations from systematic reviews. Gen. Hosp. Psychiatry 31, 206–219 (2009).
n n
65
Presents the various types of psychological interventions for the management of chronic pain.
75 Kroenke K, Krebs EE, Bair MJ:
Restorative sleep predicts the resolution of chronic widespread pain: results from the EPIFUND study. Rheumatology (Oxford) 47, 1809–1813 (2008).
Hypothalamic–pituitary–adrenal stress axis function and the relationship with chronic widespread pain and its antecedents. Arthritis Res. Ther. 7, R992–R1000 (2005).
56 Diatchenko L, Anderson AD, Slade GD et al.:
74
64 Davies KA, Macfarlane GJ, Nicholl BI et al.:
53 Houghton LA, Fell C, Whorwell PJ, Jones I,
Sudworth DP, Gale JD: Effect of a secondgeneration a2d ligand (pregabalin) on visceral sensation in hypersensitive patients with irritable bowel syndrome. Gut 56, 1218–1225 (2007).
n
Review
Discusses the various aspects of genetic modulation of pain and analgesics. Younger J, Mackey S: Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study. Pain Med. 10, 663–672 (2009).
82 Pogatzki-Zahn EM, Englbrecht JS,
Schug SA: Acute pain management in patients with fibromyalgia and other diffuse chronic pain syndromes. Curr. Opin. Anaesthesiol. 22, 627–633 (2009). n
Discusses the various strategies for acute postoperative pain management in patients with chronic pain.
www.futuremedicine.com
187
Widespread pain in temporomandibular disorders
Practice Points
Pei Feng Lim†1, William Maixner1 & Asma A Khan1 It is important to recognize that many chronic pain conditions are comorbid and, therefore, result in a
state of chronic widespread pain in many patients. Temporomandibular disorders is one of the most extensively studied chronic pain conditions in terms of
its comorbidity with chronic widespread pain and fibromyalgia. These comorbid conditions share several common features including increased pain sensitivity, fatigue
and sleep difficulties. Failure to effectively diagnose and manage comorbid pain conditions will negatively impact the
treatment response. In the out-patient setting, self-administered questionnaires and quantitative sensory testing can aid in
the diagnosis of chronic widespread pain. Patients with chronic widespread pain can be effectively managed in multidisciplinary pain clinics.
SUMMARY
Chronic widespread pain (CWP) represents pain involving several regions of the body. Various psychological and social risk factors such as poor general health status, sleep disturbance, fatigue and high psychological distress have been identified for the development of CWP. Numerous chronic pain conditions are comorbid, resulting in the development of CWP in many of these patients. Temporomandibular disorder is one of the most extensively studied chronic musculoskeletal pain condition in terms of its comorbidity with CWP and fibromyalgia. It has been proposed that these comorbid pain disorders share common denominators, including exposure to certain environmental events, elevated psychological distress, pain amplification and genetic predisposition. Increased awareness of CWP is important for improved diagnoses and more effective pain management. Patients with CWP can be effectively managed in multidisciplinary pain clinics. Three distinct patterns of pain distribution, namely localized, regional and widespread pain, are generally recognized [1,2] . Chronic widespread pain (CWP) represents pain
involving several regions of the body [3] . The point prevalence of CWP in the general pop ulation is estimated to be 11.2% [4] . Various psychological and social risk factors have been
Center for Neurosensory Disorders, University of North Carolina at Chapel Hill, 2054 Old Dental Building, CB 7455, Chapel Hill, NC 27599, USA † Author for correspondence: Tel.: +1 919 966 0684; Fax: +1 919 966 3683; [email protected] 1
10.2217/PMT.11.3 © 2011 Future Medicine Ltd
Pain Manage. (2011) 1(2), 181–187
ISSN 1758-1869
181
Review Lim, Maixner & Khan identified as risk factors for the future develop ment of CWP. These include poor general health status, sleep disturbance, fatigue and high psychological distress [5] . A small pro portion of individuals with CWP reportedly have multiple symptoms since childhood [6] , and children with behavioral problems or other somatic symptoms may be at increased risk [7] . Both increased and decreased mortality have been reported in people with CWP [8,9] . The predictors of the development of CWP include the number of painful regions at baseline [10] , and psychosocial factors such as somatiza tion [11] , health-seeking behavior and poor sleep [12] . However, the most important clini cal risk factor for chronic pain at a specific site appears to be pain in itself [13] . Von Korff et al. reported that the presence of a pain condition at baseline was a more consistent predictor of subsequent risks of developing a new pain con dition than the severity or chronicity of depres sive symptoms [14] . Therefore, chronic pain is rarely present at a single body site [15] . Complex persistent pain conditions (CPPCs) [9] , also known as functional pain syndromes, share similarities in terms of clini cal pain complaints [16] . These comorbid con ditions include, but are not limited to, fibro myalgia (FM), irritable bowel syndrome (IBS), temporomandibular disorders (TMD), vulvar vestibulitis (formerly known as vulvodynia), chronic headache, interstitial cystitis and chronic tinnitus. Irrespective of the peripheral pain location, CPPCs are probably regulated in a similar fashion [17] . Diatchenko et al. pro posed that these idiopathic pain disorders share common denominators [18] , including exposure to certain environmental events [19] , elevated psychological distress [20] , pain amplification [21] and genetic predisposition [22] . These pathways of vulnerability are interactive and influence the risk of pain onset and persistence. In the light of current scientific knowledge, what were once ‘medically unexplained symptoms’ and ‘functional somatic syndromes’ have become ‘CPPCs’ and ‘central sensitivity syndromes’ [23] . CWP is a cardinal feature of CPPCs. Temporomandibular disorder is a musculo skeletal pain condition affecting the temporo mandibular joints, masticatory muscles and/or associated structures [24] . It is one of the most extensively studied CPPCs with respect to comorbidity, pain mechanisms and risk fac tors [9] . In the next section, we will elaborate on
182
Pain Manage. (2011) 1(2)
the comorbidity of TMD with CWP and FM to illustrate the link between pain in a localized bodily area and widespread body pain. TMD & CWP Various studies have reported that facial pain is comorbid with widespread bodily pain [2] , including FM [25] , vulvar vestibulitis [26] and lower back pain [27] . The presence of pain out side the masticatory system is a known risk fac tor for the development of TMD [14] . A prospec tive study reported that, after adjusting for age, gender, education and depression severity, peo ple with a pain condition at baseline were more likely to report the onset of TMD pain over a 3‑year follow-up period compared with those without a pain condition at baseline (adjusted odds ratios of 3.7) [14] . Another study demon strated that subjects who developed TMD more frequently reported experience of joint, back, chest and menstrual pain at baseline and at the onset of TMD as compared with those subjects who did not develop this disorder [28] . Over a 2‑year period, signs of TMD at baseline pre dicted the onset of spinal pain, and spinal pain at baseline predicted the onset of TMD [29] . In addition, Korszun et al. found that 67% of their cohort of TMD subjects reported an onset of generalized pain symptoms before the onset of facial pain [20] . Macfarlane et al. found that pain in parts of the body other than the head lead to a threefold increase in the risk of develop ing TMD [19] . Studies evaluating the relation ship between TMD and its comorbidities have also identified a correlation between the fre quency/severity of the comorbidity and TMD. Wiesinger et al. reported that the prevalence of TMD symptoms and headaches increased with an increase in the frequency or severity of spinal pain and vice versa [30] . These findings suggest that it would be inappropriate to con sider TMD in isolation; instead, regional and widespread chronic pain conditions represent ‘overlapping’ conditions and should be consid ered as part of a ‘continuum’ rather than dis tinct entities with distinct etiologies [1] . In fact, the presence of one pain condition at baseline has been demonstrated to be associated with a fourfold increased risk of developing TMD [14] , and one of the strongest predictors for the onset of chronic TMD was CWP [31] . Raphael et al. reported that the occurrence of TMD with widespread body pain may impact the manage ment of such patients, because patients with
future science group
Widespread pain in temporomandibular disorders CWP are more likely to have more persistent and debilitating facial pain than those with no history of widespread pain [32] . TMD & FM While the diagnosis of FM is commonly based on the American College of Rheumatology cri teria of widespread pain and tenderness in at least 11 out of 18 musculoskeletal sites (tender points) for at least 3 months [33] , it has been effectively argued that tender points are merely markers of distress and severity and that FM represents one end of the widespread chronic pain continuum [34] . This led to the recently revised and simplified American College of Rheumatology criteria for the diagnosis of FM, which are based on the presence of widespread pain and symptoms for at least 3 months [35] . While FM has been defined as a form of CWP with widespread allodynia to pressure pain [36] , the relationship between these two entities is not completely clear [1] . Many view FM as a clinically distinct syndrome; although current literature suggest that FM is at the severe end of the CWP spectrum. Studies evaluating the overlap between FM and TMD report that 35.4–97.0% of FM patients have signs and symptoms of TMD [37] , while the prevalence of FM in TMD patients was an estimated 52% [38] . Similarities reported in both conditions included comparable clinical pain reports [39] , common symptoms, such as sleep difficulty and fatigue [21] , and psychopathology, such as depression and anxiety disorder [21,40] , again suggesting that TMD pain in FM patients may be an extension of the CWP rather than a separate entity. CWP: underlying mechanisms Several lines of evidence indicate that altera tions in central pain signaling play an impor tant role in the onset and/or exacerbation of CWP [41] . Temporal summation and diffuse noxious inhibitory control (DNIC) are com monly used to investigate central nociceptive processing in chronic pain patients. Temporal summation refers to enhanced pain intensity in response to repetitive noxious stimulation [42] . Patients with FM demonstrate abnormal tempo ral summation [43] and, for TMD patients, this enhanced temporal summation is not usually limited to the area of clinical pain [44] . This led Wolfe et al. to suggest that jaw pain may be a marker for general pain increase and symptom
future science group
Review
sensitivity [37] . DNIC refers to a phenomenon of counter-irritation whereby pain perception from one nociceptive stimulus is significantly inhibited by a second nociceptive stimulus administered at a distant site. In a recent study comparing DNIC in patients diagnosed with IBS or TMD with healthy controls, a painful conditioning stimulus (foot immersion in a noxious cold water bath) was used to moder ate pain elicited by a focal thermal stimulus to the hand [45] . Unlike the healthy controls, patients with TMD or IBS did not experience a significant decrease in pain intensity. Reduced DNIC [46] and enhanced temporal summation [47] have also been demonstrated in patients with FM and chronic headaches. Taken together, these studies suggest generalized hyperexcitabil ity of the central nociceptive system in patients with CPPCs. In addition, centrally acting medi cations, such as antidepressants, exert an anal gesic effect independent of their antidepressant effect in chronic pain patients [48] , providing further evidence supporting dysfunctions in central nociceptive processing in CPPCs [49] . Alterations in the sympathetic nervous sys tem function have also been observed in patients with TMD, FM and IBS [50] . These alterations include increased sympathetic nervous system drive at rest and an attenuated sympathetic ner vous system-mediated response to challenges, such as postural changes and exercise [50] . Several studies have demonstrated that patients with FM and TMD have lower levels of nor epinephrine at rest and have a deficient norepi nephrine response to stress as compared with pain-free controls [51] . A recent double-blind, crossover, placebo-controlled trial reported that proponalol, a b‑adrenergic antagonist, reduced the total number of painful sites and pain rating in patients with TMD and FM [52] . Pregabalin, an anticonvulsant drug that reduces the synaptic release of neurotransmitters, such as norepineph rine, glutamate and substance P, had a signifi cant analgesic effect in FM and IBS patients [53] . These studies, among others, provide substantial evidence that abnormalities in the function of the hypothalamic–pituitary–adrenal axis is one of the hallmarks of CPPC [54] . Recently, reduc tion in levels of anti-inflammatory cytokines was reported in patients with CWP [55] . Human genetic studies have revealed associa tions between genetic polymorphisms and the development of chronic pain syndromes [22,56,57] . Genetic variants are known to influence the
www.futuremedicine.com
183
Review Lim, Maixner & Khan expression and function of local mediators as well as nociceptive signaling pathways, neuro plasticity and mechanisms influencing mood [58,59,60] . It has been proposed that common functional polymorphisms in genes known to influence the processing and perception of pain represent areas of genetic vulnerability that, when coupled to environmental triggers, con tribute to enhanced pain perception, psychologi cal dysfunction, risk of onset and persistence of TMD, and related idiopathic pain disorders [22] . Three genetic variants of the gene encoding cat echolamine-O-methyltransferase designated as low, average and high pain sensitivity haplotypes were recently identified [22] . The presence of even a single low pain sensitivity haplotype reduces the risk of developing TMD by 2.3‑fold. Future prospective studies are required to investigate the genetic vulnerability, and shared physical, psychological and social risk factors associated with the onset and maintenance of CWP. Clinical implications In a recent editorial published in Pain, Croft et al. cautioned readers that “anyone setting out to study a particular association between two pain syndromes can be both reassured (you will find it) and cautioned (there will be nothing spe cial about the result)” [61] . As discussed earlier, these comorbid conditions share several com mon features, including increased pain sensitiv ity, fatigue and sleep difficulties, which often result in missed diagnosis. Patients presenting with ‘unexplained’ syndromes are often treated symptomatically while coexisting comorbidi ties are ignored, thereby resulting in failure of treatment and perpetuation of the problem [62] . This probably explains the increased number of consultations for musculoskeletal and nonmusculoskeletal problems in people with CWP than in those with no pain, for example [63] . Restorative sleep has been demonstrated to pre dict the resolution of CWP [64] . Focusing on reducing pain symptoms in a particular body region without attention to comorbid condi tions, such as poor sleep quality, will invariably result in treatment failure. Therefore, increased awareness of the overlap between the various CPPCs is important for improved diagnoses and more effective pain management. Various simple self-administered question naires are available to aid in the assessment of possible comorbid pain conditions. An example is the Fibromyalgia Rapid Screening
184
Pain Manage. (2011) 1(2)
Tool (FiRST), which is a six-item inventory requiring ‘yes’/‘no’ responses with a sensitivity of 90.5% and a specificity of 85.7% in the detec tion of FM [65] . The ID Migraine™ screener is a three-item questionnaire requiring ‘yes’/‘no’ responses with a positive predictive value of 93% [66] . Assessment of associated symptoms such as depression and anxiety [67] , somatiza tion [68] , insomnia [69] , and fatigue [70] can also be assessed by various validated short question naires. Novel ‘markers’ of CWP include quanti tative sensory testing measures, such as assess ment of the pressure pain threshold, tender point counts [71] , thermal pain perception [72] and temporal summation [43] . Patients with CWP can be very satisfacto rily managed at a multidisciplinary pain clinic. Interdisciplinary consultations, which have become the rule rather than the exception, are invaluable owing to the complex nature of the biopsychosocial factors underlying CWP. Therefore, it is not surprising that a chronic pain patient may perhaps receive management simultaneously from a psychologist, an anes thesiologist, a physical therapist, a neurologist and a dental (orofacial) pain specialist. Various psychological interventions, such as cognitive behavioral therapy, have been repeatedly docu mented to be efficacious in the management of CWP [73] . Pharmacotherapeutics, rehabilita tion medicine and various regional analgesic techniques or procedures are often pursued a longside standard care. Pharmacotherapy for CWP often includes a combination of various analgesics with dif ferent mechanisms of action, complementary pharmacokinetics and multiple sites of action along the pain pathway. This results in a syner gistic analgesic effect along with a (hopefully) reduced adverse event profile [74] . Examples of commonly used pain medications include antidepressants, anticonvulsants and simple analgesics [75] . Recent investigations reported good efficacy of duloxetine and milnacip rain in CWP [76–78] . Other promising agents include sodium oxybate, dopamine agonists, synthetic cannabinoids and NMDA antago nists. A recent randomized controlled clinical trial investigating the pharmacogenetic effect of catecholamine-O-methyltransferase on treatment response to propranolol in patients with chronic musculoskeletal pain found that catecholamine-O-methyltransferase haplotypes may serve as genetic predictors of treatment
future science group
Widespread pain in temporomandibular disorders outcome, identifying the subgroup of patients who will or will not benefit from propranolol therapy [79] . Future studies need to address the impact of genetic modulation on the effects of analgesics used in chronic pain management [80] . In one study, baseline erythrocyte sedimen tation rate reportedly predicted over 80% of the variance in response to low-dose naltrexone in FM, indicating the possible usefulness of this test in identifying a subgroup of FM patients responsive to this therapy [81] . Another chal lenging area lies in the management of postop erative pain in patients with CWP due to the increased risk of postoperative acute and pro longed pain. Multimodal approaches that have been recommended include the use of phar macotherapeutics targeted at reducing central sensitization, regional analgesia techniques and psychological supportive measures [82] . Conclusion & future perspective Chronic widespread pain is a feature of CPPCs (i.e., TMD, IBS and FM), which are comorbid pain disorders that share numerous common pathways of vulnerability, including pain Bibliography
7
Papers of special note have been highlighted as: of interest of considerable interest n
amplification, elevated psychological distress and genetic predisposition. Failure to recognize these comorbid idiopathic pain disorders will negatively impact diagnosis and, thus, the treat ment response. Various validated self-admin istered questionnaires can assist in the ‘detec tion’ of the presence of such comorbidities. The m anagement of patients with CWP is best carried out at a multidisciplinary pain clinic. Future perspective studies are needed to investigate the genetic vulnerability, and shared physical, psychological and social risk factors associated with the onset and maintenance of CWP. Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.
Jones GT, Silman AJ, Macfarlane GJ: Predicting the onset of widespread body pain among children. Arthritis Rheum. 48, 2615–2621 (2003).
12 Gupta A, Silman AJ, Ray D et al.: The role of
psychosocial factors in predicting the onset of chronic widespread pain: results from a prospective population-based study. Rheumatology (Oxford) 46, 666–671 (2007).
n n
1
2
3
4
Macfarlane GJ: Generalized pain, fibromyalgia and regional pain: an epidemiological view. Baillieres Best Pract. Res. Clin. Rheumatol. 13, 403–414 (1999). Turp JC, Kowalski CJ, O’Leary N, Stohler CS: Pain maps from facial pain patients indicate a broad pain geography. J. Dent. Res. 77, 1465–1472 (1998). Cieza A, Stucki G, Weigl M et al.: ICF core sets for chronic widespread pain. J. Rehabil. Med. 63–68 (2004). Croft P, Rigby AS, Boswell R, Schollum J, Silman A: The prevalence of chronic widespread pain in the general population. J. Rheumatol. 20, 710–713 (1993).
5
Bergman S: Psychosocial aspects of chronic widespread pain and fibromyalgia. Disabil. Rehabil. 27, 675–683 (2005).
6
Jones GT, Silman AJ, Power C, Macfarlane GJ: Are common symptoms in childhood associated with chronic widespread body pain in adulthood? Results from the 1958 British Birth Cohort Study. Arthritis Rheum. 56, 1669–1675 (2007).
future science group
8
9
n n
10
11
Review
Macfarlane GJ, McBeth J, Silman AJ: Widespread body pain and mortality: prospective population based study. BMJ 323, 662–665 (2001). Maixner W: Temporomandibular joint disorders. In: Functional Pain Syndromes: Presentation and Pathophysiology. Mayer EA, Bushnell MC (Eds). IASP Press, Seattle, WA, USA (2009).
13 Smith BH, Macfarlane GJ, Torrance N:
Epidemiology of chronic pain, from the laboratory to the bus stop: time to add understanding of biological mechanisms to the study of risk factors in population-based research? Pain 127, 5–10 (2007). 14
Highlights temporomandibular disorder as a complex persistent pain condition. A summary of current research on the pathophysiology of temporomandibular disorders is presented.
Von Korff M, LeResche L, Dworkin S: First onset of common pain symptoms: a prospective study of depression as a risk factor. Pain 55, 251–258 (1993).
15
Bergman S, Herrstrom P, Jacobsson LT, Petersson IF: Chronic widespread pain: a three year followup of pain distribution and risk factors. J. Rheumatol. 29, 818–825 (2002).
Carnes D, Parsons S, Ashby D et al.: Chronic musculoskeletal pain rarely presents in a single body site: results from a UK population study. Rheumatology (Oxford) 46, 1168–1170 (2007).
16
Von Korff M, Dworkin SF, Le Resche L, Kruger A: An epidemiologic comparison of pain complaints. Pain 32, 173–183 (1988).
17
Grossi ML, Goldberg MB, Locker D, Tenenbaum HC: Irritable bowel syndrome patients versus responding and nonresponding temporomandibular disorder patients: a neuropsychologic profile comparative study. Int. J. Prosthodont. 21, 201–209 (2008).
McBeth J, Macfarlane GJ, Benjamin S, Silman AJ: Features of somatization predict the onset of chronic widespread pain: results of a large population-based study. Arthritis Rheum. 44, 940–946 (2001).
www.futuremedicine.com
185
Review Lim, Maixner & Khan 18
n n
19
Diatchenko L, Nackley AG, Slade GD, Fillingim RB, Maixner W: Idiopathic pain disorders – pathways of vulnerability. Pain 123, 226–230 (2006). Review of idiopathic pain disorders that presents a proposed model for pathways of vulnerability for the development of chronic pain. Macfarlane TV, Gray RJM, Kincey J, Worthington HV: Factors associated with the temporomandibular disorder, pain dysfunction syndrome (PDS): Manchester case-control study. Oral Dis. 7, 321–330 (2001).
20 Korszun A, Papadopoulos E, Demitrack M,
21
28 Lim PF, Smith S, Bhalang K, Slade GD,
Maixner W: Development of temporomandibular disorders is associated with greater bodily pain experience. Clin. J. Pain 26, 116–120 (2010). Reciprocal influence on the incidence of symptoms in trigeminally and spinally innervated areas. Eur. J. Pain 14, 366–371 (2010). Wanman A: Does a dose–response relation exist between spinal pain and temporomandibular disorders? BMC Musculoskelet. Disord. 10, 28 (2009).
32 Raphael KG, Marbach JJ, Klausner J:
Myofascial face pain. Clinical characteristics of those with regional vs. widespread pain. J. Am. Dent. Assoc. 131, 161–171 (2000). American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum. 33, 160–172 (1990).
Genetic basis for individual variations in pain perception and the development of a chronic pain condition. Hum. Mol. Genet. 14, 135–143 (2005).
34 Wolfe F: The relation between tender points
and fibromyalgia symptom variables: evidence that fibromyalgia is not a discrete disorder in the clinic. Ann. Rheum. Dis. 56, 268–271 (1997).
a new paradigm and group nosology for fibromyalgia and overlapping conditions, and the related issue of disease versus illness. Semin. Arthritis Rheum. 37, 339–352 (2008).
25 Balasubramaniam R, de Leeuw R, Zhu H,
Nickerson RB, Okeson JP, Carlson CR: Prevalence of temporomandibular disorders in fibromyalgia and failed back syndrome patients: a blinded prospective comparison study. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 104, 204–216 (2007). 26 Zolnoun DA, Rohl J, Moore CG,
Perinetti-Liebert C, Lamvu GM, Maixner W: Overlap between orofacial pain and vulvar vestibulitis syndrome. Clin. J. Pain 24, 187–191 (2008). 27 Wiesinger B, Malker H, Englund E,
Wanman A: Back pain in relation to musculoskeletal disorders in the jaw-face: a matched case-control study. Pain 131, 311–319 (2007).
Major psychological disorders in acute and chronic TMD: an initial examination. J. Am. Dent. Assoc. 127, 1365–1370 (1996). 41 Vierck CJ Jr: Mechanisms underlying
development of spatially distributed chronic pain (fibromyalgia). Pain 124, 242–263 (2006). 42 Vierck CJ Jr, Cannon RL, Fry G, Maixner W,
Whitsel BL: Characteristics of temporal summation of second pain sensations elicited by brief contact of glabrous skin by a preheated thermode. J. Neurophysiol. 78, 992–1002 (1997). 43 Staud R, Robinson ME, Price DD: Temporal
summation of second pain and its maintenance are useful for characterizing widespread central sensitization of fibromyalgia patients. J. Pain 8, 893–901 (2007). 44 Sarlani E, Greenspan JD: Why look in the
33 Wolfe F, Smythe HA, Yunus MB et al.: The
22 Diatchenko L, Slade GD, Nackley AG et al.:
186
Aggarwal VR, Macfarlane GJ, Farragher TM, McBeth J: Risk factors for onset of chronic oro-facial pain – results of the North Cheshire oro-facial pain prospective population study. Pain 149, 354–359 (2010).
Aaron LA, Burke MM, Buchwald D: Overlapping conditions among patients with chronic fatigue syndrome, fibromyalgia, and temporomandibular disorder. Arch. Intern. Med. 160, 221–227 (2000).
Orofacial Pain. Guidelines for Assessment, Diagnosis, and Management. de Leeuw R (Ed.). Quintessence Publishing Co. Inc., Hanover Park, IL, USA (2008).
40 Gatchel RJ, Garofalo JP, Ellis E, Holt C:
30 Wiesinger B, Malker H, Englund E,
31
24 The American Academy of Orofacial Pain:
The incidence of pain in the muscles of mastication in patients with fibromyalgia. J. Mass Dent. Soc. 47, 8–12 (1998).
29 Marklund S, Wiesinger B, Wanman A:
Engleberg C, Crofford L: The relationship between temporomandibular disorders and stress-associated syndromes. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 86, 416–420 (1998).
23 Yunus MB: Central sensitivity syndromes:
39 Pennacchio EA, Borg-Stein J, Keith DA:
35
Wolfe F, Clauw DJ, Fitzcharles MA et al.: The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res. (Hoboken) 62, 600–610 (2010).
36 Coster L, Kendall S, Gerdle B, Henriksson C,
Henriksson KG, Bengtsson A: Chronic widespread musculoskeletal pain – a comparison of those who meet criteria for fibromyalgia and those who do not. Eur. J. Pain 12, 600–610 (2008). 37 Wolfe F, Katz RS, Michaud K: Jaw pain: its
prevalence and meaning in patients with rheumatoid arthritis, osteoarthritis, and fibromyalgia. J. Rheumatol. 32, 2421–2428 (2005) 38 Leblebici B, Pektas ZO, Ortancil O,
Hurcan EC, Bagis S, Akman MN: Coexistence of fibromyalgia, temporomandibular disorder, and masticatory myofascial pain syndromes. Rheumatol. Int. 27, 541–544 (2007).
Pain Manage. (2011) 1(2)
brain for answers to temporomandibular disorder pain? Cells Tissues Organs 180, 69–75 (2005). 45
King CD, Wong F, Currie T, Mauderli AP, Fillingim RB, Riley JL 3rd: Deficiency in endogenous modulation of prolonged heat pain in patients with irritable bowel syndrome and temporomandibular disorder. Pain 143, 172–178 (2009).
46 de Souza JB, Potvin S, Goffaux P, Charest J,
Marchand S: The deficit of pain inhibition in fibromyalgia is more pronounced in patients with comorbid depressive symptoms. Clin. J. Pain 25, 123–127 (2009). 47 Desmeules JA, Cedraschi C, Rapiti E et al.:
Neurophysiologic evidence for a central sensitization in patients with fibromyalgia. Arthritis Rheum. 48, 1420–1429 (2003). 48 Perrot S, Javier RM, Marty M, Le Jeunne C,
Laroche F: Is there any evidence to support the use of anti-depressants in painful rheumatological conditions? Systematic review of pharmacological and clinical studies. Rheumatology (Oxford) 47, 1117–1123 (2008). 49 McQuay HJ, Carroll D, Glynn CJ:
Dose-response for analgesic effect of amitriptyline in chronic pain. Anaesthesia 48, 281–285 (1993). 50 Giske L, Vollestad NK, Mengshoel AM,
Jensen J, Knardahl S, Roe C: Attenuated adrenergic responses to exercise in women with fibromyalgia – a controlled study. Eur. J. Pain 12, 351–360 (2008).
future science group
Widespread pain in temporomandibular disorders 51
Martinez-Lavin M: Biology and therapy of fibromyalgia. Stress, the stress response system, and fibromyalgia. Arthritis Res. Ther. 9(4), 216 (2007).
52
Light KC, Bragdon EE, Grewen KM, Brownley KA, Girdler SS, Maixner W: Adrenergic dysregulation and pain with and without acute b‑blockade in women with fibromyalgia and temporomandibular disorder. J. Pain 10, 542–552 (2009).
unexplained: do they have common associated factors? Int. J. Epidemiol. 35, 468–476 (2006). 63 Kadam UT, Thomas E, Croft PR: Is chronic
widespread pain a predictor of all-cause morbidity? A 3 year prospective population based study in family practice. J. Rheumatol. 32, 1341–1348 (2005).
54 McBeth J, Chiu YH, Silman AJ et al.:
55
66 Lipton RB, Dodick D, Sadovsky R et al.:
Uceyler N, Valenza R, Stock M, Schedel R, Sprotte G, Sommer C: Reduced levels of antiinflammatory cytokines in patients with chronic widespread pain. Arthritis Rheum. 54, 2656–2664 (2006).
67 Lowe B, Wahl I, Rose M et al.: A 4-item
Three major haplotypes of the b2 adrenergic receptor define psychological profile, blood pressure, and the risk for development of a common musculoskeletal pain disorder. Am. J. Med. Genet. B Neuropsychiatr. Genet. 141B(5), 449–462 (2006). 57 Hocking LJ, Smith BH, Jones GT, Reid DM,
Strachan DP, Macfarlane GJ: Genetic variation in the b2-adrenergic receptor but not catecholamine-O-methyltransferase predisposes to chronic pain: results from the 1958 British Birth Cohort Study. Pain 149(1), 143–151 (2010), Erratum in 150(1), 210 (2010). 58 Diatchenko L, Nackley AG, Tchivileva IE,
Shabalina SA, Maixner W: Genetic architecture of human pain perception. Trends Genet. 23(12), 605–613 (2007). 59 Foulkes T, Wood JN: Pain genes. PLoS Genet.
4(7), e1000086 (2008). 60 Tremblay J, Hamet P: Genetics of pain,
opioids, and opioid responsiveness. Metabolism 59(Suppl. 1). S5–S8 (2010). 61
Perrot S, Bouhassira D, Fermanian J: Development and validation of the Fibromyalgia Rapid Screening Tool (FiRST). Pain 150, 250–256 (2010).
Croft P, Dunn KM, Von Korff M: Chronic pain syndromes: you can’t have one without another. Pain 131, 237–238 (2007).
62 Aggarwal VR, McBeth J, Zakrzewska JM,
Lunt M, Macfarlane GJ: The epidemiology of chronic syndromes that are frequently
future science group
Ozaki N, Kurita K: Effectiveness of milnacipran for the treatment of chronic pain in the orofacial region. Clin. Neuropharmacol. 33, 79–83 (2010). 77 Kyle JA, Dugan BD, Testerman KK:
Milnacipran for treatment of fibromyalgia. Ann Pharmacother. 44, 1422–1429 (2010). 78 Wright CL, Mist SD, Ross RL, Jones KD:
Duloxetine for the treatment of fibromyalgia. Expert Rev. Clin. Immunol. 6, 745–756 (2010).
68 Kroenke K, Spitzer RL, Williams JB:
The PHQ‑15: validity of a new measure for evaluating the severity of somatic symptoms. Psychosom. Med. 64, 258–266 (2002).
79 Tchivileva IE, Lim PF, Smith SB et al.:
Effect of catechol-O-methyltransferase polymorphism on response to propranolol therapy in chronic musculoskeletal pain: a randomized, double-blind, placebocontrolled, crossover pilot study. Pharmacogenet. Genomics 20, 239–248 (2010).
69 Violani C, Devoto A, Lucidi F, Lombardo C,
Russo PM: Validity of a short insomnia questionnaire: the SDQ. Brain Res. Bull. 63, 415–421 (2004). 70 Hadzi-Pavlovic D, Hickie IB, Wilson AJ,
Davenport TA, Lloyd AR, Wakefield D: Screening for prolonged fatigue syndromes: validation of the SOFA scale. Soc. Psychiatry Psychiatr. Epidemiol. 35, 471–479 (2000). 71 Gupta A, McBeth J, Macfarlane GJ et al.:
Pressure pain thresholds and tender point counts as predictors of new chronic widespread pain in somatising subjects. Ann. Rheum. Dis. 66, 517–521 (2007).
80 Lotsch J, Geisslinger G, Tegeder I:
Genetic modulation of the pharmacological treatment of pain. Pharmacol. Ther. 124, 168–184 (2009). n n
81
72 Fernandez-de-las-Penas C, Galan-del-Rio F,
Ortega-Santiago R, Jimenez-Garcia R, Arendt-Nielsen L, Svensson P: Bilateral thermal hyperalgesia in trigeminal and extra-trigeminal regions in patients with myofascial temporomandibular disorders. Exp. Brain Res. 202, 171–179 (2010). 73 Kroner-Herwig B: Chronic pain syndromes
and their treatment by psychological interventions. Curr. Opin. Psychiatry 22, 200–204 (2009).
Presents a summary of meta-analyses and systematic reviews published since 2005 examining pharmacotherapy for chronic pain management.
76 Ito M, Kimura H, Yoshida K, Kimura Y,
A self-administered screener for migraine in primary care: the ID Migraine validation study. Neurology 61, 375–382 (2003). measure of depression and anxiety: validation and standardization of the Patient Health Questionnaire-4 (PHQ-4) in the general population. J. Affect Disord. 122, 86–95 (2010).
Raffa RB: Pharmacology of oral combination analgesics: rational therapy for pain. J. Clin. Pharm. Ther. 26, 257–264 (2001). Pharmacotherapy of chronic pain: a synthesis of recommendations from systematic reviews. Gen. Hosp. Psychiatry 31, 206–219 (2009).
n n
65
Presents the various types of psychological interventions for the management of chronic pain.
75 Kroenke K, Krebs EE, Bair MJ:
Restorative sleep predicts the resolution of chronic widespread pain: results from the EPIFUND study. Rheumatology (Oxford) 47, 1809–1813 (2008).
Hypothalamic–pituitary–adrenal stress axis function and the relationship with chronic widespread pain and its antecedents. Arthritis Res. Ther. 7, R992–R1000 (2005).
56 Diatchenko L, Anderson AD, Slade GD et al.:
74
64 Davies KA, Macfarlane GJ, Nicholl BI et al.:
53 Houghton LA, Fell C, Whorwell PJ, Jones I,
Sudworth DP, Gale JD: Effect of a secondgeneration a2d ligand (pregabalin) on visceral sensation in hypersensitive patients with irritable bowel syndrome. Gut 56, 1218–1225 (2007).
n
Review
Discusses the various aspects of genetic modulation of pain and analgesics. Younger J, Mackey S: Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study. Pain Med. 10, 663–672 (2009).
82 Pogatzki-Zahn EM, Englbrecht JS,
Schug SA: Acute pain management in patients with fibromyalgia and other diffuse chronic pain syndromes. Curr. Opin. Anaesthesiol. 22, 627–633 (2009). n
Discusses the various strategies for acute postoperative pain management in patients with chronic pain.
www.futuremedicine.com
187
