- Email: [email protected]
Idiopathic masticatory muscle pain
Commentary
Idiopathic Masticatory Muscle Pain A Convergence of Multiple Systems? Charles G. Widmer
nderstanding the pathophysiology of acute and chronic muscle pain requires an integration of new knowledge in the areas of muscle receptors, central pain processing, central sensitization or neuroplasticity, neuroendocrine function, and neuroimmunology. The timely Focus article by Svensson has incorporated recent advances in some of these areas to formulate a model of muscle pain associated with masticatory muscles. As a part of this model, he has proposed that acute and chronic pain conditions are associated with distinctly different etiologies. Acute pain is proposed to be associated with peripheral muscle trauma, local ischemia, and an increase in muscle tone, whereas chronic pain is attributed to central neural changes that are responsible for expanded receptor fields and hyperexcitability. Although these hypotheses do incorporate much of the new information on these general topics and raise pertinent questions that are testable, there are specific issues that need further consideration as alternative hypotheses. As part of his working model to explain the production and maintenance of peripheral muscle pain, Svensson references the vicious cycle theory and maintains it as the predominant feature of his model. This hypothesis has been described by many authors [2,4,14,18,21], but the essential features include the reciprocal link between masticatory muscle pain and spasm or dysfunction of the muscle that continues as a "vicious cycle."The original hypothesis reported by Travell et al. described a relationship between muscle pain and muscle spasm that was self-perpetuating, creating apain-spasm-pain cycle [21]; however, as was pointed out by Svensson,
U
From the Department of Oral and Maxillofacial Surgery and Diagnostic Sciences, College of Dentistry, University of Florida, Gainesville, FL. Reprint requests: Charles G. Widmer, DDS, Department of Oral and Maxillofacial Surgery and Diagnostic Sciences, Box 100416, JHMHSC, University of Florida, Gainesville, FL 32610-0416.
170
the lack of elevated electromyographic recordings at rest in patients with chronic muscle pain conditions has prompted many recent reviews to conclude that muscle hyperactivity is not associated with chronic muscle pain conditions [1,3,10,12,17]. In the light of this new evidence, Svensson referenced the modified vicious cycle theory by Mense [13] to incorporate electrically silent contractu res. These contractu res are hypothesized to be locally expressed within muscle and may occur secondary to increased activity of gamma motoneurons, focal ischemia, or direct muscle fiber trauma, resulting in release of vasoactive substances and edema. Although some aspects of these modifications are difficult to test experimentally, there already is evidence that does not support portions of this modified theory. For example, there is evidence that the monosynaptic (stretch) reflex amplitude is not different between patients and controls, refuting the presence of an increased drive to trigeminal gamma motoneurons in patients with masticatory muscle pain [8,11,16]. Therefore, an increased muscle tone via this system is probably not present and would not contribute to local ischemia within the muscle. A second issue involves the assumption that muscle trauma is involved in masticatory muscle pain. Only a small percentage of patients present with overt trauma to masticatory muscles, and it is questionable whether "microtrauma" to muscle fibers secondary to bruxism is a prominent feature in these patients. Magnetic resonance imaging of the masticatory muscles does not demonstrate edema within the muscle and does not show the high water content indicative of muscle fiber damage and edema similar to magnetic resonance imaging of limb muscles [19,20]. Additional evidence for the presence of damaged muscle fibers is required to support this theory whether the trauma is overt, associated with eccentric contractions, or occurs at very high levels of concentric contraction (Le., bruxism or a form of postexercise muscle soreness). Rather than requiring overt muscle fiber damage to initiate these muscle pain con-
Pain Forum 6(3): 170-172, 1997
COMMENTARY/widmer
ditions, alternative hypotheses might be considered that incorporate new findings in neuroendocrinology and neuroimmunology. Very little information is available to assess systemic/local factors involved in masticatory muscle pain conditions. More is known, however, about another chronic and more generalized muscle pain condition termed fibromyalgia that has many characteristics similar to those of masticatory muscle pain conditions [24]. Common characteristics include a predominantly female patient population (2:1 ratio in fibromyalgia, 2-3:1 ratio in TMD), localized sites of muscle/tendon tenderness, sleep disturbances, association with higher anxiety or stress levels, and normal routine laboratory tests [6,22,25]. Differences involve the chronicity of the muscle pain (> 3 months in fibromyalgia, intermittent for myalgia associated with TMD) and the widespread involvement of tender palpation sites in fibromyalgia (upper and lower extremities). Although it is possible that these two groups may represent different pathophysiologic conditions, the similarity of the physical characteristics, psychosocial traits, and systemic/local findings suggests that these conditions may involve common mechanisms of muscle pain with different durations. Therefore, the results of fibromyalgia patient-eontrol studies may provide the basis for initiating hypothesis formation for the etiology or pathogenesis of masticatory muscle pain. Fibromyalgia patients, when compared with age and sex-matched control groups, have shown differences in the reactivity of the hypothalamic-pituitary-adrenal (HPA) axis with high pituitary adrenocorticotropic hormone release and adrenal hyporesponsiveness [5,7]. In addition, lower levels of somatomedin C and hyperprolactemia have been reported for fibromyalgia patients. Such changes in the HPA axis could be related to high anxiety and stress as these emotional factors can directly affect the hypothalamus. Stress and anxiety are correlated with increases in adrenocorticotropic hormone release and the production of corticosteroids by the adrenal glands. The chronic stimulation of the adrenals to maintain corticosteroid production could lead to the observed adrenal hyporesponsiveness. The observation that women are found to be preferentially affected with fibromyalgia and masticatory muscle pain conditions indicates a potential role for gonadal steroids in these conditions. Evidence exists that estrogen may increase pain responses and lower pain thresholds, as well as modify the effects of cortisol and insulin [15]. It is important to assay the endocrine function in muscle pain patients to determine if alterations in sex hormone levels exist and if changes in the HPA axis in masticatory muscle pain parallel changes in these factors in the more generalized fibromyalgia pain condition; however, androgen and estrogen levels have not been compared
171
in a study of appropriately age and sex-matched control subjects. In addition, if there is a hyporesponsiveness of the adrenal cortex in affected women, the available circulating androgen levels would be significantly reduced because, in women, approximately one half of androgen production occurs in the adrenal glands. Androgens have a protective role in antagonizing glucocorticoid-induced muscle atrophy and may also be involved in muscle repair/synthesis. Alterations in the immune system of fibromyalgia patients have also been documented. In one cross-sectional study, circulating lymphocyte types were reported to be increased in a subset of fibromyalgia patients. CD4+ cell numbers and CD4+/CD8+ cell ratios were found to be higher than control values in 60% of the patients [23]. This study also showed that circulating cytokine levels of interleukin-2 were elevated in 53% of patients compared with control subjects. These specific T-cell elevations may be related to neurogenic effects, such as increased beta-endorphin levels, that would increase interleukin-2 production by CD4+ cells; however, another study lacking control subjects documented a decrease of in interleukin-2 production by CD4+ cells compared with normal values [9]. The possible role of circulating inflammatory cytokines produced by lymphocytes in muscle pain has not been investigated to date. Interestingly, recent evidence suggests that increased interleukin-10 levels during pregnancy may inhibit pain in rheumatoid arthritis patients. This finding parallels the clinical observations of decreased muscle pain in pregnant patients with masticatory muscle disorders. These studies suggest that a systemic evaluation of CD4+ cell activity and inflammatory cytokine production should be pursued as these may be important parameters to measure in masticatory muscle pain patients. Taken together, these data suggest that multiple systems may be involved in the initiation or propagation of muscle pain conditions including the masticatory muscles. It is important to recognize all of these pertinent systems, in addition to potential peripheral muscle fiber injury and central nervous system alterations, to develop hypotheses that accurately reflect the signs and symptoms presented by these patients.
References 1. Ahern OK, Follick MJ, Council JR, Laser-Wolston N, Litchman H: Comparison of lumbar paravertebral EMG patterns in chronic low back pain patients and nonpatient controls. Pain 34: 153-160, 1988 2. Blasberg B, Chalmers A: Temporomandibular pain and dysfunction syndrome associated with generalized musculoskeletal pain: a retrospective study. Int J Rheumatol 16:87-90,1989
172
COMMENTARv/widmer
3. Chapman SL: A review and clinical perspective on the use of EMG and thermal biofeedback for chronic headaches. Pain 27:1-43, 1986 4. Cobb CR, deVries HA, Urban RT, Luekens CA, Bagg RJ: Electrical activity in muscle pain. Am J Phys Med 54: 80-87, 1975 5. Denderen JC, Boersma JW, Zeinstra P, Hollander Ap, Van Neerbos BR: Physiological effects of exhaustive exercise in primary fibromyalgia syndrome (PFS): is PFS a disorder of neuroendocrine reactivity? Scand J Rheumatol 21:35-37, 1992 6. Dworkin SF, Huggins KH, Le Resche L, Von Korff MR, Howard J, Truelove E, Sommers E: Epidemiology of signs and symptoms in temporomandibular disorders: clinical signs in cases and controls. J Am Dent Assoc 120: 273-281,1990 7. Ferraccioli GF, Cavalieri F, Salaffi F, Fontana S, Scita F, Nolli M, Maestri 0: Neuroendocrinologic findings in primary fibromyalgia (soft tissue chronic pain syndrome) and in other chronic rheumatic conditions (rheumatoid arthritis, low back pain). J RheumatoI17:869-873, 1990 8. Griffin CJ, Munro RR: Electromyography of the masseter and anterior temporalis muscles in patients with temporomandibular dysfunction. Arch Oral Bioi 16:929-949, 1971 9. Hader N, Rimon 0, Kinarty A, Lahat N: Altered interleukin-2 secretion in patients with primary fibromyalgia syndrome. Arthritis Rheum 34:866-872, 1991 10. Henriksson KG, Bengtsson A: Fibromyalgia: a clinical entity? Can J Physiol PharmacoI69:672-677, 1991 11. Lobbezoo F, Van Der Glas HW, Van Der Bilt A, Buchner R, Bosman F: Sensitivity of the jaw-jerk reflex in patients with myogenous temporomandibular disorders. Arch Oral Bioi 41:553-563, 1996 12. Lund Jp, Donga R, Widmer CG, Stohler CS: The painadaptation model: a discussion of the relationship between chronic musculoskeletal pain and motor activity. Can J Physiol Pharmacol 69:683-694, 1991 13. Mense S: Nociception from skeletal muscle in relation to clinical muscle pain. Pain 54:241-289,1993
14. Michler L, Bakke M, Moller E: Graphic assessment of natural mandibular movement. J Craniomand Disord Fac Oral Pain 2:97-114,1987 15. Mogil JS, Sternberg WF, Kest B, Marek P, Liebeskind JC: Sex differences in the antagonism of swim stress-induced analgesia: effects of gonadectomy and estrogen replacement. Pain 53:17-25,1993 16. Murray GM, Klineberg IJ: Electromyographic recordings of human jaw-jerk reflex characteristics evoked under standardized condition. Arch Oral Bioi 29:537-549, 1984 17. Nouwen A, Bush C: The relationship between paraspinal EMG and chronic low back pain. Pain 20:109-123,1984 18. Parker MW: A dynamic model of etiology in temporomandibular disorders. J Am Dent Assoc 120:283-290, 1990 19. Schellhas KP: MR imaging of muscles of mastication. AJR 153:847-855, 1989 20. Shellock FG, Fukunaga T, Mink JH, Edgerton VR: Exertional muscle injury: evaluationof concentric versus eccentric actions with serial MR imaging. Radiology 179: 659-664,1991 21. Travell J, Rinzler S, Herman M: Pain and disability of the shoulder and arm: treatment by intramuscular infiltration with procaine hydrochloride. JAMA 120:417-422,1942 22. Von Korff MR, Dworkin SF, Le Resche L, Kruger A: Epidemiology of temporomandibular disorders: II. TMD pain compared to other common pain sites. p. 506. In Dubner R, Gebhart GF, Bonds MR (eds): Proceedings of the Vth World Congress on Pain. Elsevier, Amsterdam, 1988 23. Wallace OJ, Bowman RL, Wormsley SB, Peter JB: Cytokines and immune regulation in patients with fibrositis. Arthritis Rheum 32:1334-1335, 1989 24. Widmer CG: Introduction: III. Chronic muscle pain syndromes: an overview. Can J Physiol Pharmacol 69: 659-661,1991 25. Wolfe F, Ross K, Anderson J, Russell IJ, Hebert L: The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum 38:19-28,1995
Idiopathic Masticatory Muscle Pain A Convergence of Multiple Systems? Charles G. Widmer
nderstanding the pathophysiology of acute and chronic muscle pain requires an integration of new knowledge in the areas of muscle receptors, central pain processing, central sensitization or neuroplasticity, neuroendocrine function, and neuroimmunology. The timely Focus article by Svensson has incorporated recent advances in some of these areas to formulate a model of muscle pain associated with masticatory muscles. As a part of this model, he has proposed that acute and chronic pain conditions are associated with distinctly different etiologies. Acute pain is proposed to be associated with peripheral muscle trauma, local ischemia, and an increase in muscle tone, whereas chronic pain is attributed to central neural changes that are responsible for expanded receptor fields and hyperexcitability. Although these hypotheses do incorporate much of the new information on these general topics and raise pertinent questions that are testable, there are specific issues that need further consideration as alternative hypotheses. As part of his working model to explain the production and maintenance of peripheral muscle pain, Svensson references the vicious cycle theory and maintains it as the predominant feature of his model. This hypothesis has been described by many authors [2,4,14,18,21], but the essential features include the reciprocal link between masticatory muscle pain and spasm or dysfunction of the muscle that continues as a "vicious cycle."The original hypothesis reported by Travell et al. described a relationship between muscle pain and muscle spasm that was self-perpetuating, creating apain-spasm-pain cycle [21]; however, as was pointed out by Svensson,
U
From the Department of Oral and Maxillofacial Surgery and Diagnostic Sciences, College of Dentistry, University of Florida, Gainesville, FL. Reprint requests: Charles G. Widmer, DDS, Department of Oral and Maxillofacial Surgery and Diagnostic Sciences, Box 100416, JHMHSC, University of Florida, Gainesville, FL 32610-0416.
170
the lack of elevated electromyographic recordings at rest in patients with chronic muscle pain conditions has prompted many recent reviews to conclude that muscle hyperactivity is not associated with chronic muscle pain conditions [1,3,10,12,17]. In the light of this new evidence, Svensson referenced the modified vicious cycle theory by Mense [13] to incorporate electrically silent contractu res. These contractu res are hypothesized to be locally expressed within muscle and may occur secondary to increased activity of gamma motoneurons, focal ischemia, or direct muscle fiber trauma, resulting in release of vasoactive substances and edema. Although some aspects of these modifications are difficult to test experimentally, there already is evidence that does not support portions of this modified theory. For example, there is evidence that the monosynaptic (stretch) reflex amplitude is not different between patients and controls, refuting the presence of an increased drive to trigeminal gamma motoneurons in patients with masticatory muscle pain [8,11,16]. Therefore, an increased muscle tone via this system is probably not present and would not contribute to local ischemia within the muscle. A second issue involves the assumption that muscle trauma is involved in masticatory muscle pain. Only a small percentage of patients present with overt trauma to masticatory muscles, and it is questionable whether "microtrauma" to muscle fibers secondary to bruxism is a prominent feature in these patients. Magnetic resonance imaging of the masticatory muscles does not demonstrate edema within the muscle and does not show the high water content indicative of muscle fiber damage and edema similar to magnetic resonance imaging of limb muscles [19,20]. Additional evidence for the presence of damaged muscle fibers is required to support this theory whether the trauma is overt, associated with eccentric contractions, or occurs at very high levels of concentric contraction (Le., bruxism or a form of postexercise muscle soreness). Rather than requiring overt muscle fiber damage to initiate these muscle pain con-
Pain Forum 6(3): 170-172, 1997
COMMENTARY/widmer
ditions, alternative hypotheses might be considered that incorporate new findings in neuroendocrinology and neuroimmunology. Very little information is available to assess systemic/local factors involved in masticatory muscle pain conditions. More is known, however, about another chronic and more generalized muscle pain condition termed fibromyalgia that has many characteristics similar to those of masticatory muscle pain conditions [24]. Common characteristics include a predominantly female patient population (2:1 ratio in fibromyalgia, 2-3:1 ratio in TMD), localized sites of muscle/tendon tenderness, sleep disturbances, association with higher anxiety or stress levels, and normal routine laboratory tests [6,22,25]. Differences involve the chronicity of the muscle pain (> 3 months in fibromyalgia, intermittent for myalgia associated with TMD) and the widespread involvement of tender palpation sites in fibromyalgia (upper and lower extremities). Although it is possible that these two groups may represent different pathophysiologic conditions, the similarity of the physical characteristics, psychosocial traits, and systemic/local findings suggests that these conditions may involve common mechanisms of muscle pain with different durations. Therefore, the results of fibromyalgia patient-eontrol studies may provide the basis for initiating hypothesis formation for the etiology or pathogenesis of masticatory muscle pain. Fibromyalgia patients, when compared with age and sex-matched control groups, have shown differences in the reactivity of the hypothalamic-pituitary-adrenal (HPA) axis with high pituitary adrenocorticotropic hormone release and adrenal hyporesponsiveness [5,7]. In addition, lower levels of somatomedin C and hyperprolactemia have been reported for fibromyalgia patients. Such changes in the HPA axis could be related to high anxiety and stress as these emotional factors can directly affect the hypothalamus. Stress and anxiety are correlated with increases in adrenocorticotropic hormone release and the production of corticosteroids by the adrenal glands. The chronic stimulation of the adrenals to maintain corticosteroid production could lead to the observed adrenal hyporesponsiveness. The observation that women are found to be preferentially affected with fibromyalgia and masticatory muscle pain conditions indicates a potential role for gonadal steroids in these conditions. Evidence exists that estrogen may increase pain responses and lower pain thresholds, as well as modify the effects of cortisol and insulin [15]. It is important to assay the endocrine function in muscle pain patients to determine if alterations in sex hormone levels exist and if changes in the HPA axis in masticatory muscle pain parallel changes in these factors in the more generalized fibromyalgia pain condition; however, androgen and estrogen levels have not been compared
171
in a study of appropriately age and sex-matched control subjects. In addition, if there is a hyporesponsiveness of the adrenal cortex in affected women, the available circulating androgen levels would be significantly reduced because, in women, approximately one half of androgen production occurs in the adrenal glands. Androgens have a protective role in antagonizing glucocorticoid-induced muscle atrophy and may also be involved in muscle repair/synthesis. Alterations in the immune system of fibromyalgia patients have also been documented. In one cross-sectional study, circulating lymphocyte types were reported to be increased in a subset of fibromyalgia patients. CD4+ cell numbers and CD4+/CD8+ cell ratios were found to be higher than control values in 60% of the patients [23]. This study also showed that circulating cytokine levels of interleukin-2 were elevated in 53% of patients compared with control subjects. These specific T-cell elevations may be related to neurogenic effects, such as increased beta-endorphin levels, that would increase interleukin-2 production by CD4+ cells; however, another study lacking control subjects documented a decrease of in interleukin-2 production by CD4+ cells compared with normal values [9]. The possible role of circulating inflammatory cytokines produced by lymphocytes in muscle pain has not been investigated to date. Interestingly, recent evidence suggests that increased interleukin-10 levels during pregnancy may inhibit pain in rheumatoid arthritis patients. This finding parallels the clinical observations of decreased muscle pain in pregnant patients with masticatory muscle disorders. These studies suggest that a systemic evaluation of CD4+ cell activity and inflammatory cytokine production should be pursued as these may be important parameters to measure in masticatory muscle pain patients. Taken together, these data suggest that multiple systems may be involved in the initiation or propagation of muscle pain conditions including the masticatory muscles. It is important to recognize all of these pertinent systems, in addition to potential peripheral muscle fiber injury and central nervous system alterations, to develop hypotheses that accurately reflect the signs and symptoms presented by these patients.
References 1. Ahern OK, Follick MJ, Council JR, Laser-Wolston N, Litchman H: Comparison of lumbar paravertebral EMG patterns in chronic low back pain patients and nonpatient controls. Pain 34: 153-160, 1988 2. Blasberg B, Chalmers A: Temporomandibular pain and dysfunction syndrome associated with generalized musculoskeletal pain: a retrospective study. Int J Rheumatol 16:87-90,1989
172
COMMENTARv/widmer
3. Chapman SL: A review and clinical perspective on the use of EMG and thermal biofeedback for chronic headaches. Pain 27:1-43, 1986 4. Cobb CR, deVries HA, Urban RT, Luekens CA, Bagg RJ: Electrical activity in muscle pain. Am J Phys Med 54: 80-87, 1975 5. Denderen JC, Boersma JW, Zeinstra P, Hollander Ap, Van Neerbos BR: Physiological effects of exhaustive exercise in primary fibromyalgia syndrome (PFS): is PFS a disorder of neuroendocrine reactivity? Scand J Rheumatol 21:35-37, 1992 6. Dworkin SF, Huggins KH, Le Resche L, Von Korff MR, Howard J, Truelove E, Sommers E: Epidemiology of signs and symptoms in temporomandibular disorders: clinical signs in cases and controls. J Am Dent Assoc 120: 273-281,1990 7. Ferraccioli GF, Cavalieri F, Salaffi F, Fontana S, Scita F, Nolli M, Maestri 0: Neuroendocrinologic findings in primary fibromyalgia (soft tissue chronic pain syndrome) and in other chronic rheumatic conditions (rheumatoid arthritis, low back pain). J RheumatoI17:869-873, 1990 8. Griffin CJ, Munro RR: Electromyography of the masseter and anterior temporalis muscles in patients with temporomandibular dysfunction. Arch Oral Bioi 16:929-949, 1971 9. Hader N, Rimon 0, Kinarty A, Lahat N: Altered interleukin-2 secretion in patients with primary fibromyalgia syndrome. Arthritis Rheum 34:866-872, 1991 10. Henriksson KG, Bengtsson A: Fibromyalgia: a clinical entity? Can J Physiol PharmacoI69:672-677, 1991 11. Lobbezoo F, Van Der Glas HW, Van Der Bilt A, Buchner R, Bosman F: Sensitivity of the jaw-jerk reflex in patients with myogenous temporomandibular disorders. Arch Oral Bioi 41:553-563, 1996 12. Lund Jp, Donga R, Widmer CG, Stohler CS: The painadaptation model: a discussion of the relationship between chronic musculoskeletal pain and motor activity. Can J Physiol Pharmacol 69:683-694, 1991 13. Mense S: Nociception from skeletal muscle in relation to clinical muscle pain. Pain 54:241-289,1993
14. Michler L, Bakke M, Moller E: Graphic assessment of natural mandibular movement. J Craniomand Disord Fac Oral Pain 2:97-114,1987 15. Mogil JS, Sternberg WF, Kest B, Marek P, Liebeskind JC: Sex differences in the antagonism of swim stress-induced analgesia: effects of gonadectomy and estrogen replacement. Pain 53:17-25,1993 16. Murray GM, Klineberg IJ: Electromyographic recordings of human jaw-jerk reflex characteristics evoked under standardized condition. Arch Oral Bioi 29:537-549, 1984 17. Nouwen A, Bush C: The relationship between paraspinal EMG and chronic low back pain. Pain 20:109-123,1984 18. Parker MW: A dynamic model of etiology in temporomandibular disorders. J Am Dent Assoc 120:283-290, 1990 19. Schellhas KP: MR imaging of muscles of mastication. AJR 153:847-855, 1989 20. Shellock FG, Fukunaga T, Mink JH, Edgerton VR: Exertional muscle injury: evaluationof concentric versus eccentric actions with serial MR imaging. Radiology 179: 659-664,1991 21. Travell J, Rinzler S, Herman M: Pain and disability of the shoulder and arm: treatment by intramuscular infiltration with procaine hydrochloride. JAMA 120:417-422,1942 22. Von Korff MR, Dworkin SF, Le Resche L, Kruger A: Epidemiology of temporomandibular disorders: II. TMD pain compared to other common pain sites. p. 506. In Dubner R, Gebhart GF, Bonds MR (eds): Proceedings of the Vth World Congress on Pain. Elsevier, Amsterdam, 1988 23. Wallace OJ, Bowman RL, Wormsley SB, Peter JB: Cytokines and immune regulation in patients with fibrositis. Arthritis Rheum 32:1334-1335, 1989 24. Widmer CG: Introduction: III. Chronic muscle pain syndromes: an overview. Can J Physiol Pharmacol 69: 659-661,1991 25. Wolfe F, Ross K, Anderson J, Russell IJ, Hebert L: The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum 38:19-28,1995