Pain Effects of Glutamate Injections Into Human Jaw or Neck Muscles

Aims: To document and compare the intensity, localization, and quality of pain evoked by glutamate injections into the human mas-seter or splenius muscles and to determine the effect of glutamate-evoked pain on the pressure pain thresholds (PPTs) in both jaw and neck muscles. Methods: Twenty-six healthy men were given painful injections of glutamate (1.0 mol/L) and control injections of iso-tonic saline (0.165 mol/L) into the masseter and splenius muscles. The subjects rated the perceived intensity of pain on a visual analog scale (VAS), drew the area of the pain on maps of the face and neck, and filled out a Danish version of the McGill Pain Questionnaire (MPQ). PPTs were used to assess the sensitivity of the masseter and splenius muscles to mechanical stimuli (n = 11). Results: Glutamate injection into the masseter or splenius evoked pain lasting almost 10 minutes. Peak pain intensity usually occurred within 2 minutes of the injection, and VAS scores of peak pain were significantly higher for the masseter muscle compared with the sple-nius muscle (paired t test, P = .003). The pain area from the mas-seter injections did not extend into the neck region, although in some subjects the pain from the neck region extended into the tem-poral region. There were no significant relationships between the area of perceived pain and the VAS pain scores (Pearson correla-tion, P ＞ .297). Glutamate-evoked pain in either the masseter or splenius muscles was associated with significant decreases in mas-seter or splenius PPTs, respectively (2-wayANOVAs, P ＜.016). Isometric saline injections were almost pain-free and caused no PPT changes. Conclusion: The data suggest that the masseter muscle is more sensitive to glutamate injections and mechanical stimuli than the splenius muscle. The relatively limited overlap between the sen-sory manifestations of pain from masseter and splenius muscles may have potential implications for diagnosis and management of myofascial pain complaints in the craniofacial and neck region.

cervical spine pain disorders; experimental muscle pain; glutamate; temporomandibular disorders; trigeminal pain

1. Carlsson GE, LeResche L. Epidemiology of temporo-mandibular disorders. In: Sessle BJ, Bryant PS, Dionne RA (eds). Progress in Pain Research and Management. Seattle: IASP Press, 1995:211–226.

2. Drangsholt M, LeResche L. Temporomandibular disorder pain. In: Crombie IK, Croft PR, Linton SJ, LeResche L, Von Korff M (eds). Epidemiology of Pain. Seattle: IASP Press, 1999:497–506.

3. Sessle BJ. The neural basis of temporomandibular joint and masticatory muscle pain. J Orofac Pain 1999;13: 238–245.

4. Stohler CS. Muscle-related temporomandibular disorders. J Orofac Pain 1999;13:273–284.

5. Svensson P, Graven-Nielsen T. Craniofacial muscle pain: Review of mechanisms and clinical manifestations. J Orofac Pain 2001;15:117–145.

6. Svensson P, Sessle BJ. Orofacial pain. In: Miles TS, Nauntofte B, Svensson P (eds). Clinical Oral Physiology. Copenhagen: Quintessence, 2004:93–139.

7. Fricton JR, Kroening R, Haley D, Siegert R. Myofascial pain syndrome of the head and neck: A review of clinical characteristics of 164 patients. Oral Surg Oral Med Oral Pathol 1985;60:615–623.

8. Travell JG, Simons DG. Myofascial Pain and Dysfunction. The Trigger Point Manual. Baltimore: Williams & Wilkins, 1983.

9. Wright EF. Referred craniofacial pain patterns in patients with temporomandibular disorder. J Am Dent Assoc 2000;131:1307–1315.

10. Stiesch-Scholz M, Fink M, Tschernitschek H. Comorbidity of internal derangement of the temporomandibular joint and silent dysfunction of the cervical spine. J Oral Rehabil 2003;30:386–391.

11. Sipilä K, Zitting P, Siira P, et al. Temporomandibular disorders, occlusion, and neck pain in subjects with facial pain: A case-control study. Cranio 2002;20:158–164.

12. Visscher CM, Lobbezoo F, de Boer W, van der Zaag J, Naeije M. Prevalence of cervical spinal pain in craniomandibular pain patients. Eur J Oral Sci 2001;109:76–80.

13. de Wijer A, de Leeuw JR, Steenks MH, Bosman F. Temporomandibular and cervical spine disorders. Self-reported signs and symptoms. Spine 1996;21:1638–1646.

14. de Wijer A, Steenks MH, Bosman F, Helders PJ, Faber J. Symptoms of the stomatognathic system in temporo-mandibular and cervical spine disorders. J Oral Rehabil 1996;23:733–741.

15. Sessle BJ, Hu JW, Amano N, Zhong G. Convergence of cutaneous, tooth pulp, visceral, neck and muscle afferents onto nociceptive and non-nociceptive neurones in trigeminal subnucleus caudalis (medullary dorsal horn) and its implication for referred pain. Pain 1986;27:219–235.

16. Hu JW, Yu X-M, Vernon H, Sessle BJ. Excitatory effects on neck and jaw muscle activity of inflammatory irritant applied to cervical paraspinal tissues. Pain 1993;55:243–250.

17. Sessle BJ. Acute and chronic craniofacial pain: Brainstem mechanisms of nociceptive transmission and neuroplasticity, and their clinical correlates. Crit Rev Oral Biol Med 2000;11:57–91.

18. Clark GT, Browne PA, Nakano M, Yang Q. Co-activation of sternocleidomastoid muscles during maximum clenching. J Dent Res 1993;72:1499–1502.

19. Ehrlich R, Garlick D, Ninio M. The effect of jaw clenching on the electromyographic activities of 2 neck and 2 trunk muscles. J Orofac Pain 1999;13:115–120.

20. Eriksson PO, Haggman-Henrikson B, Nordh E, Zafar H. Co-ordinated mandibular and head-neck movements during rhythmic jaw activities in man. J Dent Res 2000;79:1378–1384.

21. Cairns BE, Hu JW, Arendt-Nielsen L, Sessle BJ, Svensson P. Sex-related differences in human pain and rat afferent discharge evoked by injection of glutamate into the masseter muscle. J Neurophysiol 2001;86:782–791.

22. Cairns BE, Gambarota G, Svensson P, Arendt-Nielsen L, Berde CB. Glutamate-induced sensitization of rat masseter muscle fibers. Neuroscience 2002;109:389–399.

23. Cairns BE, Svensson P, Wang K, et al. Activation of peripheral NMDA receptors contributes to human pain and rat afferent discharges evoked by injection of glutamate into the masseter muscle. J Neurophysiol 2003;90:2098–2105.

24. Svensson P, Cairns BE, Wang K, et al. Glutamate-induced sensitization of pressure pain thresholds in human masseter muscle. Pain 2003;101:221-227.

25. Cairns BE, Sessle BJ, Hu JW. Evidence that excitatory amino acid receptors within the temporomandibular joint region are involved in the reflex activation of the jaw mus-cles. J Neurosci 1998;18:8056–8064.

26. Dworkin SF, LeResche L. Research Diagnostic Criteria for Temporomandibular Disorders: Review, criteria, examinations and specifications, critique. J Craniomandib Disord 1992;6:301–355.

27. Dao TTT, LeResche L. Gender differences in pain. J Orofac Pain 2000;14:169–184.

28. Svensson P, Arendt-Nielsen L, Nielsen H, Larsen JK. Effect of chronic and experimental jaw muscle pain on pain-pressure thresholds and stimulus-response curves. J Orofac Pain 1995;9:347–356.

29. Drewes AM, Helweg-Larsen S, Petersen P, et al. McGill Pain Questionnaire translated into Danish: Experimental and clinical findings. Clin J Pain 1993;9:80–87.

30. Melzack R. The McGill Pain Questionnaire: Major prop-erties and scoring methods. Pain 1975;1:277–300.

31. McMillan AS, Lawson ET. Effect of tooth clenching and jaw opening on pain-pressure thresholds in the human jaw muscles. J Orofac Pain 1994;8:250–257.

32. Wang K, Svensson P, Arendt-Nielsen L. Effect of tonic muscle pain on short-latency jaw-stretch reflexes in humans. Pain 2000;88:189–197.

33. Jensen K, Norup M. Experimental pain in human temporal muscle induced by hypertonic saline potassium and acidity. Cephalalgia 1992;12:101–106.

34. Graven-Nielsen T, Babenko V, Svensson P, Arendt-Nielsen L. Experimentally-induced muscle pain induces hypoalgesia in heterotopic deep tissues, but not in homo-topic deep tissues. Brain Res 1998;787:203–210.

35. Bogduk N, Jensen R. Anatomy and pathology of tension-type headache. In: Olesen J, Tfelt-Hansen P, Welch KMA (eds). The Headaches, ed 2. Philadelphia: Lippincott Williams & Wilkins, 2000:551–559.

36. Campbell DG, Parsons CM. Referred head pain and its concomitants. J Nerv Mental Dis 1944;99:544–551.

37. Feinstein B, Langton JNK, Jameson RM, Schiller F. Experiments on pain referred from deep somatic tissues. J Bone Joint Surg 1954;36:981–997.

38. Hu JW, Sessle BJ, Raboisson P, Dallel R, Woda A. Stimulation of craniofacial muscle afferents induces prolonged facilitatory effects in trigeminal nociceptive brainstem neurones. Pain 1992;48:53–60.

39. Chung SC, Um BY, Kim HS. Evaluation of pressure pain threshold in head and neck muscle by electronic algometer: Intrarater and interrater reliability. J Craniomandib Pract 1992;10:28–34.

40. Kim HS, Chung SC, Kim YK, Lee SW. Pain-pressure threshold in the head and neck region of episodic tension-type headache patients. J Orofac Pain 1995;9:357–364.

41. Sand T, Zwart JA, Helde G, Bovim G. The reproducibility of cephalic pain pressure thresholds in control subjects and headache patients. Cephalalgia 1997;17:748–755.

42. Babenko V, Graven-Nielsen T, Svensson P, Drewes AM, Jensen TS, Arendt-Nielsen L. Experimental human muscle pain and muscular hyperalgesia induced by combinations of serotonin and bradykinin. Pain 1999;82:1–8.

43. Babenko V, Svensson P, Graven-Nielsen T, Drewes AM, Jensen TS, Arendt-Nielsen L. Duration and distribution of experimental muscular hyperalgesia in humans following combined infusions of serotonin and bradykinin. Brain Res 2000;853:275–281.

44. Ernberg M, Lundeberg T, Kopp S. Pain and allodynia/hyperalgesia induced by intramuscular injection of serotonin in patients with fibromyalgia and healthy individuals. Pain 2000;85:31–39.

45. Ernberg M, Lundeberg T, Kopp S. Effect of propranolol and granisetron on experimentally induced pain and allodynia/hyperalgesia by intramuscular injection of serotonin into the human masseter muscle. Pain 2000;84:339–346.

46. Svensson P, Cairns BE, Wang K, Arendt-Nielsen L. Injection of nerve growth factor into human masseter muscle evokes long-lasting mechanical allodynia and hyperalgesia. Pain 2003;104:241–247.

47. MacIver MB, Tanelian DL. Structural and functional specialization of A delta and C fiber free nerve endings innervating rabbit corneal epithelium. J Neurosci 1993;13: 4511–4524.

48. Carlton SM, Hargett GL, Coggeshall RE. Localization and activation of glutamate receptors in unmyelinated axons of rat glabrous skin. Neurosci Lett 1995;197:25–28.

49. Jackson DL, Graff CB, Richardson JD, Hargreaves KM. Glutamate participates in the peripheral modulation of thermal hyperalgesia in rats. Eur J Pharmacol 1995;284:321–325.

50. Lawand NB, McNearney T, Westlund KN. Amino acid release into the knee joint: Key role in nociception and inflammation. Pain 2000;86:69–74.

51. Lawand NB, Willis WD, Westlund KN. Excitatory amino acid receptor involvement in peripheral nociceptive transmission in rats. Eur J Pharmacol 1997;324:169–177.

52. McNearney T, Speegle D, Lawand N, Lisse J, Westlund KN. Excitatory amino acid profiles of synovial fluid from patients with arthritis. J Rheumatol 2000;27:739–745.

53. Du J, Zhou S, Coggeshall RE, Carlton SM. N-methyl-D-aspartate-induced excitation and sensitization of normal and inflamed nociceptors. Neurosci 2003;118:547–562.

54. Neugebauer V, Carlton SM. Peripheral metabotropic glutamate receptors as drug targets for pain relief. Expert Opin Ther Targets 2002;6:349–361.