Complex Regional Pain Syndrome in the Head and Neck: A Review of the Literature

This article reviews the features of complex regional pain syndrome (CRPS), including its pathophysiology, diagnosis, and treatment. CRPS is a pathology that has been described as occurring almost always in a limb, but this review provides a focus on the literature reporting cases in which the face, head, and neck were affected. Very few cases were found that seemed to meet the International Association for the Study of Pain criteria for the disease. The clinical characteristics were similar to those of CRPS elsewhere in the body, with the main features being burning pain, hyperalgesia, and hyperesthesia starting after a trauma to the craniofacial region. Physical signs were reported less frequently. The treatment of choice was seen to be a series of stellate ganglion anesthetic blocks, which resulted in a good outcome in all the cases reviewed.

causalgia; complex regional pain syndromes; facial pain; facial pain syndromes; reflex sympathetic dystrophy

1. Mitchell S, Morehouse C, Keane W. Gunshot Wounds and Other Injuries of the Nerves. Philadelphia: Lippincott, 1864.

2. Mitchell S. Injuries of Nerves and Their Consequences, ed

2. New York: Dover, 1965.

3. Elfenbaum A. Causalgia in dentistry: An abandoned pain syndrome. Oral Surg Oral Med Oral Pathol 1954;7: 594–600.

4. Leriche R. De la causalgie, envisage comme une nevrite due sympathique et desson traitement par la denudation et l’excision des plexus nerveux periartieriels. Presse Med 1916;24:178–180.

5. Leriche R. La Chirurgie del la douleur. Paris: Massont, 1939.

6. Evans J. Reflex sympathetic dystrophy. Surg Clin North Am 1946;26:780–790.

7. Merskey H, Bogduk N. Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms, ed 2. Seattle: IASP Press, 1994.

8. Stanton-Hicks M, Janig W, Hassenbusch S, Haddox JD, Boas R, Wilson P. Reflex sympathetic dystrophy: Changing concepts and taxonomy [see comments]. Pain 1995;63(1):127–133.

9. Wasner G, Backonja MM, Baron R. Traumatic neuralgias: Complex regional pain syndromes (reflex sympathetic dystrophy and causalgia): Clinical characteristics, pathophysiological mechanisms and therapy. Neurol Clin 1998;16(4):851–868.

10. Stanton-Hicks M, Baron R, Boas R, et al. Complex regional pain syndromes: Guidelines for therapy [see comments]. Clin J Pain 1998;14(2):155–166.

11. Okeson J. Neuropathic pains. In: Okeson J (ed). Bell’s Orofacial Pains, ed 5. Chicago: Quintessence, 1995: 403–456.

12. Gregg JM. Studies of traumatic neuralgias in the maxillofacial region: Surgical pathology and neural mechanisms. J Oral Maxillofac Surg 1990;48(3):228–237, discussion 238–239.

13. Woolf C, Mannion R. Neuropathic pain: Etiology, symptoms, mechanisms, and management. N Engl Pain Assoc Newslett 2000;5(2):4–11.

14. Ochoa J, Torebjork HE, Culp WJ, Schady W. Abnormal spontaneous activity in single sensory nerve fibers in humans. Muscle Nerve 1982;5(9S):S74–S77.

15. Devor M. The pathophysiology of damaged peripheral nerves. In: Wall P, Melzack R (eds). Textbook of Pain, ed

3. New York: Churchill Livingstone, 1994:79–100.

16. Seltzer Z, Devor M. Ephaptic transmission in chronically damaged peripheral nerves. Neurology 1979;29(7): 1061–1064.

17. Granit R, Leksell L, Skoglund C. Fibre interaction in injured or compressed region of nerve. Brain 1944; 67:125–140.

18. Doupe T, Cullen C, Chance G. Post-traumatic pain in the causalgic syndrome. J Neurol Neurosurg Psychiatry 1944;7:33–48.

19. Nathan P. On the pathogenesis of causalgia in peripheral nerve injuries. Brain 1947;70:145–170.

20. McLachlan EM, Janig W, Devor M, Michaelis M. Peripheral nerve injury triggers noradrenergic sprouting within dorsal root ganglia. Nature 1993;363(6429): 543–546.

21. Jänig W, Levine JD, Michaelis M. Interactions of sympathetic and primary afferent neurons following nerve injury and tissue trauma. Prog Brain Res 1996;113:161–184.

22. Baron R, Levine JD, Fields HL. Causalgia and reflex sympathetic dystrophy: Does the sympathetic nervous system contribute to the generation of pain? Muscle Nerve 1999;22(6):678–695.

23. Hanowell ST, Kennedy SF. Phantom tongue pain and causalgia: Case presentation and treatment. Anesth Analg 1979;58(5):436–438.

24. Melzack R. Phantom limb pain: Implications for treatment of pathologic pain. Anesthesiology 1971;35(4): 409–419.

25. Livingston W. Pain Mechanisms. New York: Plenum Press, 1976.

26. Gerad R. The physiology of pain—Abnormal neuron states in causalgia and related phenomena. Anesthesiology 1951;12:1–13.

27. Livingston W. Pain Mechanisms; A Physiologic Interpretation of Causalgia and Its Related States. New York: Macmillan, 1943.

28. Anderson LS, Black RG, Abraham J, Ward AA Jr. Neuronal hyperactivity in experimental trigeminal deafferentation. J Neurosurg 1971;35(4):444–452.

29. Westrum LE, Black RG. Changes in the synapses of the spinal trigeminal nucleus after ipsilateral rhizotomy. Brain Res 1968;11(3):706–709.

30. Bonica JJ. Causalgia and other reflex sympathetic dystrophies. In: Bonica JJ (ed). Management of Pain, ed 2. Philadelphia: Lea & Febiger, 1990:220–243.

31. Woda A, Pionchon P. Topical review: A unified concept of idiopathic orofacial pain: Pathophysiologic features. J Orofac Pain 2000;14:196–212.

32. Woolf CJ, Shortland P, Coggeshall RE. Peripheral nerve injury triggers central sprouting of myelinated afferents. Nature 1992;355(6355):75–78.

33. Miki K, Fukuoka T, Tokunaga A, Noguchi K. Calcitonin gene-related peptide increase in the rat spinal dorsal horn and dorsal column nucleus following peripheral nerve injury: Up-regulation in a subpopulation of primary afferent sensory neurons. Neuroscience 1998;82(4): 1243–1252.

34. Neumann S, Doubell TP, Leslie T, Woolf CJ. Inflammatory pain hypersensitivity mediated by phenotypic switch in myelinated primary sensory neurons. Nature 1996;384(6607):360–364.

35. Cho HJ, Kim DS, Lee NH, et al. Changes in the alpha 2-adrenergic receptor subtypes gene expression in rat dorsal root ganglion in an experimental model of neuropathic pain. Neuroreport 1997;8(14):3119–3122.

36. Gonzales R, Goldyne ME, Taiwo YO, Levine JD. Production of hyperalgesic prostaglandins by sympathetic postganglionic neurons. J Neurochem 1989;53(5): 1595–1598.

37. Mackinnon S, Dellon A. Painful sequelae in peripheral nerve injury. In: Mackinnon S, Dellon A (eds). Surgery of the Peripheral Nerve. New York: Thieme Medical Publishers, 1988:457–492.

38. Wall P, Gutnick M. Ongoing activity in peripheral nerves: The physiology and pharmacology of impulses originating from aneuroma. Exp Neurol 1974;43(3):580–593.

39. Smith KJ, McDonald WI. Spontaneous and mechanically evoked activity due to central demyelinating lesion. Nature 1980;286(5769):154–155.

40. Calvin WH, Devor M, Howe JF. Can neuralgias arise from minor demyelination? Spontaneous firing, mechanosensitivity, and afterdischarge from conducting axons. Exp Neurol 1982;75(3):755–763.

41. Baker M, Bostock H. Ectopic activity in demyelinated spinal root axons of the rat. J Physiol 1992;451:539–552.

42. Jaeger B, Singer E, Kroening R. Reflex sympathetic dystrophy of the face. Report of two cases and a review of the literature.Arch Neurol 1986;43(7):693–695.

43. Johnson LR, Westrum LE, Canfield RC. Ultrastructural study of transganglionic degeneration following dental lesions. Exp Brain Res 1983;52(2):226–234.

44. Gobel S. An electron microscopic analysis of the transsynaptic effects of peripheral nerve injury subsequent to tooth pulp extirpations on neurons in laminae I and II of the medullary dorsal horn. J Neurosci 1984;4(9): 2281–2290.

45. Gregg JM. Posttraumatic pain: Experimental trigeminal neuropathy. J Oral Surg 1971;29(4):260–267.

46. Aldskogius H, Arvidsson J. Nerve cell degeneration and death in the trigeminal ganglion of the adult rat following peripheral nerve transection. J Neurocytol 1978;7(2): 229–250.

47. Sessle BJ. The neural basis of temporomandibular joint and masticatory muscle pain. J Orofac Pain 1999;13(4): 238–245.

48. 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(1):57–91.

49. Hu JW, Sessle BJ. Effects of tooth pulp deafferentation on nociceptive and nonnociceptive neurons of the feline trigeminal subnucleus caudalis (medullary dorsal horn). J Neurophysiol 1989;61(6):1197–1206.

50. Wall PD, Devor M. Sensory afferent impulses originate from dorsal root ganglia as well as from the periphery in normal and nerve injured rats. Pain 1983;17(4):321–339.

51. Burchiel KJ. Spontaneous impulse generation in normal and denervated dorsal root ganglia: Sensitivity to alpha-adrenergic stimulation and hypoxia. Exp Neurol 1984;85(2):257–272.

52. DeSantis M, Duckworth JW. Properties of primary afferent neurons from muscle which are spontaneously active after a lesion of their peripheral processes. Exp Neurol 1982;75(2):261–274.

53. Khoury R, Kennedy SF, Macnamara TE. Facial causalgia: Report of case. J Oral Surg 1980;38(10):782–783.

54. Watkins LR, Wiertelak EP, Goehler LE, Smith KP, Martin D, Maier SF. Characterization of cytokine-induced hyperalgesia. Brain Res 1994;654(1):15–26.

55. Watkins LR, Maier SF, Goehler LE. Immune activation: The role of pro-inflammatory cytokines in inflammation, illness responses and pathological pain states. Pain 1995;63(3):289–302.

56. Watkins LR, Maier SF. The pain of being sick: Implications of immune-to-brain communication for understanding pain. Ann Rev Psychol 2000;51:29–57.

57. DeLeo JA, Colburn RW, Nichols M, Malhotra A. Interleukin-6-mediated hyperalgesia/allodynia and increased spinal IL-6 expression in a rat mononeuropathy model. J Interferon Cytokine Res 1996;16(9):695–700.

58. DeLeo JA, Colburn RW, Rickman AJ. Cytokine and growth factor immunohistochemical spinal profiles in two animal models of mononeuropathy. Brain Res 1997;759(1):50–57.

59. DeLeo JA, Rutkowski MD, Stalder AK, Campbell IL. Transgenic expression of TNF by astrocytes increases mechanical allodynia in a mouse neuropathy model. Neuroreport 2000;11(3):599–602.

60. Merrill RL. Orofacial pain mechanisms and their clinical application. Dent Clin North Am 1997;41(2):167–188.

61. Blumberg H, Jänig W. Clinical manifestation of reflex sympathetic dystrophy and sympathetically maintained pain. In: Wall PD, Melzack R (eds). Textbook of Pain, ed

3. Edinburgh: Churchill Livingstone, 1994:685–697.

62. Oyen WJ, Arntz IE, Claessens RM, Van der Meer JW, Corstens FH, Goris RJ. Reflex sympathetic dystrophy of the hand: An excessive inflammatory response? Pain 1993;55(2):151–157.

63. Boas RA. Complex regional pain syndromes: Symptoms, signs, and differential diagnosis. In: Jänig W, Stanton-Hicks M (eds). Progress in Pain Research and Management. Vol 6: Reflex sympathetic dystrophy: A reappraisal. Seattle: IASP Press, 1996:79–92.

64. Gibbons JJ, Wilson PR. RSD score: Criteria for the diagnosis of reflex sympathetic dystrophy and causalgia [see comments].Clin J Pain 1992;8(3):260–263.

65. Galer BS. Painful polyneuropathy. Neurol Clin 1998;16(4):791–812.

66. Bruehl S, Harden RN, Galer BS, et al. External validation of IASP diagnostic criteria for Complex Regional Pain Syndrome and proposed research diagnostic criteria. International Association for the Study of Pain. Pain 1999;81(1-2):147–154.

67. Harden RN, Bruehl S, Galer BS, et al. Complex regional pain syndrome: Are the IASP diagnostic criteria valid and sufficiently comprehensive? Pain 1999;83(2):211–219.

68. Baron R, Maier C. Reflex sympathetic dystrophy: Skin blood flow, sympathetic vasoconstrictor reflexes and pain before andafter surgical sympathectomy. Pain 1996;67(2-3):317–326.

69. Low PA, Amadio PC, Wilson PR, McManis PG, Willner

CL. Laboratory findings in reflex sympathetic dystrophy: A preliminary report. Clin J Pain 1994;10(3):235–239.

70. Chelimsky TC, Low PA, Naessens JM, Wilson PR, Amadio PC, O’Brien PC. Value of autonomic testing in reflex sympathetic dystrophy [see comments]. Mayo Clin Proc 1995;70(11):1029–1040.

71. Genant HK, Kozin F, Bekerman C, McCarty DJ, Sims J. The reflex sympathetic dystrophy syndrome. A comprehensive analysis using fine-detail radiography, photon absorptiometry, and bone and joint scintigraphy. Radiology 1975;117(1):21–32.

72. Kozin F, Genant HK, Bekerman C, McCarty DJ. The reflex sympathetic dystrophy syndrome. II. Roentgenographic and scintigraphic evidence of bilaterality and of periarticular accentuation. Am J Med 1976;60(3):332–338.

73. Holder LE, Mackinnon SE. Reflex sympathetic dystrophy in the hands: Clinical and scintigraphic criteria. Radiology 1984;152(2):517–522.

74. Kozin F, Soin JS, Ryan LM, Carrera GF, Wortmann RL. Bone scintigraphy in the reflex sympathetic dystrophy syndrome. Radiology 1981;138(2):437–443.

75. Wilson PR, Low PA, Bedder MD, Covington EC, Rauck RL. Diagnostic algorithm for complex regional pain syndrome. In: Jänig W, Stanton-Hicks M (eds). Progress in Pain Research and Management. Vol 6: Reflex sympathetic dystrophy: A reappraisal. Seattle: IASP Press, 1996:93–105.

76. Stanton-Hicks M, Raj PP, Racz GB. Use of regional anesthetic for diagnosis of reflex sympathetic dystrophy and sympathetically maintained pain: A critical evaluation. In: Jänig W, Stanton-Hicks M (eds).Progress in Pain Research and Management. Vol 6: Reflex sympathetic dystrophy: A reappraisal. Seattle: IASPPress, 1996:217–237.

77. Hassenbusch SJ, Stanton-Hicks M, Schoppa D, Walsh JG, Covington EC. Long-term results of peripheral nerve stimulation for reflex sympathetic dystrophy. J Neurosurg 1996;84(3):415–423.

78. Headley B. Historical perspective of causalgia. Management of sympathetically maintained pain. Phys Ther 1987;67(9):1370–1374.

79. Kiroglu MM, Sarpel T, Ozberk P, Soylu L, Cetik F, Aydogan LB. Reflex sympathetic dystrophy following neck dissections. AmJ Otolaryngol 1997;18(2):103–106.

80. Poplawski ZJ, Wiley AM, Murray JF. Post-traumatic dystrophy of the extremities. J Bone Joint Surg [Am] 1983;65(5):642–655.

81. Figuerola M, Bruera O, and Leston J. Reflex sympathetic dystrophy of the face: An unusual cause of facial pain. Headache Q 2000;11(2):135–137.

82. Nesathurai S, Harvey DT, Schatz SW. Gustatory facial sweating subsequent to upper thoracic sympathectomy. Arch Phys Med Rehabil 1995;76(1):104–107.

83. Swerdlow M. Anticonvulsant drugs and chronic pain. Clin Neuropharmacol 1984;7(1):51–82.

84. Chabal C, Jacobson L, Mariano A, Chaney E, Britell CW. The use of oral mexiletine for the treatment of pain after peripheralnerve injury. Anesthesiology 1992;76(4): 513–517.

85. Swerdlow M. Review: The use of local anaesthetic for relief of chronic pain. Pain Clin 1988;2:3–6.

86. Max MB, Lynch SA, Muir J, Shoaf SE, Smoller B, Dubner

R. Effects of desipramine, amitriptyline, and fluoxetine on pain in diabetic neuropathy [see comments]. N Engl J Med 1992;326(19):1250–1526.

87. Mellick GA, Mellicy LB, Mellick LB. Gabapentin in the management of reflex sympathetic dystrophy [letter]. J Pain SymptomManage 1995;10(4):265–266.

88. Veldman PH, Jacobs PB. Reflex sympathetic dystrophy of the head: Case report and discussion of diagnostic criteria. J Trauma 1994;36(1):119–121.

89. Goris RJ. Treatment of reflex sympathetic dystrophy with hydroxyl radical scavengers. Unfallchirurg 1985;88(7): 330–332.

90. Shimoji K, Hokari T, Kano T, et al. Management of intractable pain with percutaneous epidural spinal cord stimulation: Differences in pain-relieving effects among diseases and sites of pain. Anesth Analg 1993;77(1): 110–116.

91. Arden RL, Bahu SJ, Zuazu MA, Berguer R. Reflex sympathetic dystrophy of the face: Current treatment recommendations. Laryngoscope 1998;108(3):437–442.

92. Kozin F, McCarty DJ, Sims J, Genant H. The reflex sympathetic dystrophy syndrome. I. Clinical and histologic studies: Evidence for bilaterality, response to corticosteroids and articular involvement. Am J Med 1976;60(3):321–331.

93. Teeple E, Ferrer EB, Ghia JN, Pallares V. Pourfour Du Petit syndrome—Hypersympathetic dysfunctional state following a direct non-penetrating injury to the cervical sympathetic chain and brachial plexus. Anesthesiology 1981;55(5):591–592.

94. Driessen JJ, van der Werken C, Nicolai JP, Crul JF. Clinical effects of regional intravenous guanethidine (Ismelin) in reflex sympathetic dystrophy. Acta Anaesthesiol Scand 1983;27(6):505–509.

95. Wang JK, Johnson KA, Ilstrup DM. Sympathetic blocks for reflex sympathetic dystrophy. Pain 1985;23(1):13–17.

96. Lynch ME, Elgeneidy AK. The role of sympathetic activity in neuropathic orofacial pain. J Orofac Pain 1996;10(4): 297–305.

97. Gerber J, Nies A. Antihypertensive agents and the drug therapy for hypertension. In: Goodman GA, Rall T, Nies A, Taylor P (eds). Goodman and Gilman’s The Pharmacological Basis of Therapeutics, ed 8. New York: Pergamon Press, 1990:784–813.

98. Benowitz N. Antihypertensive agents. In: Katzung B (ed). Basic and Clinical Pharmacology, ed 6. Norwalk, CT: Appleton & Lange, 1994:155–180.

99. Jacob LS. Cardiovascular agents. In: Williams W (ed). Pharmacology. Malvern: Harwal, 1992:95–132.

100. Hoffman B. Adrenoceptor against drugs. In: Katzung B (ed). Basic and Clinical Pharmacology, ed 6. Norwalk, CT: Appleton & Lange, 1994:138–154.

101. Hoffman B, Lefkowitz R. Catecholamines and sympathomimetic drugs. In: Goodman GA, Gilman A, Rall TW, Nies AS, TaylorP (eds). Goodman and Gilman’s The Pharmacological Basis of Therapeutics, ed 8. New York: Pergamon Press, 1990:187–220.

102. Hoffman B, Lefkowitz R. Adrenergic receptor antagonists. In: Goodman GA, Gilman A, Rall TW, Nies AS, Taylor P (eds). Goodman and Gilman’s The Pharmacological Basis of Therapeutics, ed 8. New York: Pergamon Press, 1990:221–243.

103. Jacob L. Drug affecting peripheral neurohumoral transmission. In: Williams W (ed). Pharmacology, ed 3. Malvern: Harwal, 1992:17–43.

104. Saxen MA, Campbell RL. An unusual case of sympathetically maintained facial pain complicated by telangiectasia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1995;79(4):455–458.

105. Davis KD, Treede RD, Raja SN, Meyer RA, Campbell JN. Topical application of clonidine relieves hyperalgesia in patients with sympathetically maintained pain [see comments]. Pain 1991;47(3):309–317.

106. Bingham JA. Causalgia of the face: Two cases successfully treated by sympathectomy. Br Med J 1947;1(June): 804–805.

107. Behrman S. Facial neuralgias. Br Dent J 1949;86:197–203.

108. Bongenhielm U, Boissonade FM, Westermark A, Robinson PP, Fried K. Sympathetic nerve sprouting fails to occur in the trigeminal ganglion after peripheral nerve injury in the rat. Pain 1999;82(3):283–288.

109. Benoliel R, Eliav E, Tal M. No sympathetic sprouting in rat trigeminal ganglion following painful and non-painful infraorbital nerve neuropathy. Neurosci Lett 2001;297(3):151–154.