Anesth Prog 37:129-132 1990
Neurologic Aspects of Chronic Facial Pain Raymond Maciewicz MD, PhD Associate Professor of Neurology and Neuroscience, Harvard Medical School, Boston, Massachusetts
Chronic facial pain can result from neuropathic changes associated with deafferentation. The pattern of deep afferent convergence on trigeminal cells may also relate to the pathophysiology of chronic facial pain disorders.
trigeminal rhizotomy, most of the facial skin and oral cavity are completely anesthetic. Only the most peripheral 2-3 cm of the facial skin is sensitive to noxious stimulation, although the evoked sensation is not pain. The peripheral face may therefore receive some afferent innervation from the 7th, 9th, and 10th cranial nerves as well as cervical nerves C2-C4. CHRONIC NEUROPATHIC FACIAL PAIN
A lthough there are many similarities in the organization of nociceptive transmission in the trigeminal and spinal systems, important differences between the two systems exist. Such differences may be important in the pathogenesis of certain forms of chronic facial pain, including deafferentation pain and chronic vascular face pain.
This difference in the peripheral branching pattern of trigeminal and spinal afferents may in part explain the common occurrence of neuropathic, deafferentation pain within the trigeminal system. Trigeminal nerve lesions are more frequently associated with posttraumatic dysesthesias than are spinal nerve injuries,4 and the conditions of anesthesia dolorosa and trigeminal neuralgia appear to be unique to the trigeminal system. A significant group of patients with chronic facial pain have a history of trauma to the trigeminal system that may be a source of chronic neuropathic facial pain.5 The disorder most frequently follows damage to the peripheral trigeminal branches, usually due to trauma or surgery. Posttraumatic trigeminal pain often involves the third division and the oral cavity, likely due to the frequency of oral pathology and dental surgery or extractions.6 Clinically, such patients usually have a clear history of nerve injury that preceeded the onset of pain. The pain is usually well localized to the distribution of the affected nerve. The pain usually consists of spontaneous dysesthesias and paresthesias superimposed on a more chronic, dull, aching pain. On examination, there is often evidence of a sensory loss in the region supplied by the injured nerve. This may be coupled with hypersensitivity to touch or pressure over the same area. Chronic mandibular pain in such patients is likely due to compression and neuroma formation in the involved trigeminal branches, because in some cases surgical decompression of the inferior alveolar nerve can provide substantial relief.6 However, central mechanisms may also play a role in posttraumatic facial pain. Sessle et a17 have demonstrated that simple endodontal pulpotomy in animals is associated with a reorganization and enlargement
TRIGEMINAL DISTRIBUTION
Following trigeminal root section, the insensate cutaneous region stretches from the vertex along midline to a point 1-2 cm below the chin. 1-3 Laterally, the trigeminal dermatome descends anteriorly from the vertex to the ear, across the zygoma, and down the cheek. Within the perioral region, the trigeminal dermatome includes the lips, teeth, gingiva, anterior 2/3 of the tongue, the palato-glossal fold, the uvula, and the soft palate. In addition to this cutaneous distribution, the trigeminal nerve contains afferents that provide the sensory innervation to a variety of deep tissues in the head, including the muscles of facial expression and mastication, the nasal and oral mucosae, the cornea, tongue, tooth pulp, dura mater, and external auditory meatus. In contrast to the spinal afferent system where there is significant overlap between adjacent sensory afferents, there is little functional overlap between the trigeminal dermatome and adjacent spinal or cranial nerves.2'3 After
Address correspondence to Raymond Maciewicz, MD, PhD, Spaulding Pain Rehabilitation Program, Spaulding Rehabilitation Hospital, Boston MA 02114. C 1990 by the American Dental Society of Anesthesiology
ISSN 0003-3006/90/$3.50
129
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Neurology of Facial Pain
of the receptive fields of brainstem trigeminal neurons. Such physiologic changes may persist for months after surgery, and may be associated with anatomic evidence for degeneration and plastic reorganization in the trigeminal system following tooth extraction.8 Posterior trigeminal rhizotomy also results in persistent pain referred to the anesthetic zone of the face in approximately 10% of cases.4 Following rhizotomy, there is a loss of central trigeminal afferent terminals within the trigeminal complex, and deafferented central trigeminal neurons develop an irregular spontaneous discharge. Such cells also become less responsive to iontophoretically applied inhibitory transmitters, evidence that deafferentation likely produces a reorganization of central trigeminal circuitry. Recent data9'10 show that trigeminal rhizotomy in rats also results in a change in opiate gene expression within lamina I and II neurons, with an increase in cells that express preprodynorphin and a decrease in cells that express preproenkephalin. Such deafferentation-induced changes in gene expression may partly underlie the central reorganization of trigeminal neurons that results in deafferentation pain. As noted above, anesthesia dolorosa only occurs in 10% of patients undergoing rhizotomy; it is possible that genetically determined differences in the response of central neurons to deafferentation underlies the difference in response to deafferentation in individual cases. CHRONIC VASCULAR FACIAL PAIN
Many patients with chronic, recurrent facial pain have significant vasomotor and/or autonomic accompaniments to their pain, suggesting a vascular facial pain syndrome similar to migraine or cluster headache. As many as 50% of the patients in early series" had symptoms that included facial flushing, edema, unequal pupils, lacrimation, or nasal congestion; in some there were additional migranous symptoms of photophobia and nausea, as well as arterial tendemess during attacks. In these patients the pain is usually episodic, and predominantly one-sided; nausea and photophobia may accompany attacks. Between attacks the patient is free of pain. The episodic nature of the pain with long intervening pain-free periods suggests the diagnosis of a vascular pain syndrome, although in a significant group of patients the pain can become more chronic, with daily episodes of pain. The mechanism of pain in such conditions is likely due to activation of intracranial vascular nociceptors with referral of pain to the face. Most somatosensory research in the trigeminal system has focused on the innervation of the skin and specialized organs such as the teeth and eyes. However, most chronic, clinically relevant pain in the head usually involves afferents from deeper structures, such as muscles,
Anesth Prog 37:129-132 1990
joints, and major blood vessels, as well as the nasal sinuses and oral cavity. The sensory innervation of these structures largely arises from small caliber afferents, many of which contain neuropeptides. These afferents primarily serve a nociceptive function. Often, the pain evoked by activation of such deep afferents is referred to specific regions of the face and head. For example, the major cranial vessels that supply the brain and dura are innervated by small caliber peptidergic trigeminal sensory afferents.'2 Penfield'3 observed that mechanical or thermal stimulation of dural blood vessels in humans evokes pain. This pain is not felt locally; instead it is referred to a broad region of the first trigeminal division that usually includes the forehead and ipsilateral eye. Activation of vascular nociceptors with referral of pain to the forehead is a likely mechanism for many forms of cranial vascular pain, including the pain associated with certain forms of vascular headache. 4 Stimulation of other deep cranial afferents also causes referral of pain to the face. Specific structures may evoke characteristic patterns of referral. Noxious stimulation of the muscles of mastication, for example, can cause referral of pain to the maxilla, the orbit, or the teeth, depending on the site of stimulation. 15 The referral of deep cranial pain to distant sites on the face or scalp is analogous to the referral of other forms of visceral pain at spinal levels. 16 Deep sensory afferents from muscle, the temporomandibular joint capsule, or cranial blood vessels are primarily small caliber afferents that likely contribute a major projection to nucleus candalis (NC). These deep afferents terminate on brainstem trigeminal cells that often have nociceptive cutaneous receptive fields. The convergence of deep and cutaneous afferents onto the same cells likely accounts for the phenomenon of referred pain in the trigeminal system. Strassman et al,'7 for example, have shown that a population of wide dynamic range (WDR) and nociceptive specific (NS) cells in NC are excited by stimulation of major blood vessels in the dura. These same cells also receive a nociceptive input from the skin of the first trigeminal division, usually including the ipsilateral eye and forehead. This convergence of cutaneous and vascular afferents on the same cells in NC likely explains the common referral of cranial vascular pain to the forehead and eye. Such cells may mediate the pain associated with certain forms of vascular headache, including migraine. Cells in trigeminal nucleus caudalis that receive a convergent input from blood vessels and first division of the trigeminal nerve (V1) are located primarily in lamina V. Recent studies using intracellular injection techniques18 reveal that one population of these vascular convergence cells extensively collateralizes within the spinal trigeminal complex and the adjacent reticular formation. Within lamina V the terminals of these cells contain round synaptic
Anesth Prog 37:129-132 1990
vesicles and end on dendritic spines or shafts of other neurons in lamina V. Such cells are likely important modulators of trigeminal sensory transmission within the trigeminal complex itself. Because the synaptic morphology is consistent with excitatory neurotransmission, they may be responsible for exciting other lamina V neurons. This type of trigeminal neuron could in part explain the extensive cutaneous hypersensitivity that can follow a focal noxious stimulus applied to the face. A second population of vascular convergence cells have axons that project rostrally through the trigeminothalamic tract; these cells likely relay sensations of vascular pain that reach conscious perception. Some of these cells give rise to collateral projections that terminate in the nuclei of the dorsomedial medulla, including the nucleus of the solitary tract and the border of the vagal nucleus. Vascular facial pain syndromes are often associated with prominent autonomic features, including ipsilateral facial flushing, conjunctival injection, ptosis, myosis, and rhinorrhea, as well as systemic symptoms of bradycardia and hypertension. The collateral projections to the dorsomedial medulla of trigeminal vascular relay neurons may be important in the mediation of the local and systemic autonomic responses associated with vascular pain in the face and head. Afferents from other deep structures in the head, such as the temporomandibular joint,19 the cranial muscles,20-22 and the ethmoid sinus23 also converge on trigeminal cells with cutaneous receptive fields. The cutaneous receptive fields of such cells, however, are found in all three trigeminal dermatomes and include low threshold as well as nociceptive response patterns. The pattern of convergence for these deep afferents is therefore more variable than for cranial vascular inputs. It's likely, however, that the convergence of these deep afferents on cells with cutaneous receptive fields partly explains the referral of deep cranial pain to distant sites in the face and head. "5 The overlap of deep afferent inputs to brainstem trigeminal neurons may also be relevent in the pathophysiology of chronic myofascial pain that involves the masticatory muscles.24 Chronic facial pain of many types often becomes associated with masticatory muscle tendemess and restriction of movement. Convergence of deep afferents within the trigeminal system may play an important role in the development of this syndrome.
REFERENCES 1. Cushing H: The sensory distribution of the fifth cranial nerve. Bull John Hopkins Hosp 1904;15:213-232. 2. Denny-Brown D, Yanagisawa N: The function of the descending root of the fifth nerve. Brain 1973;96:783-814.
Maciewicz 131
3. White JC, Sweet WH: Pain and the Neurosurgeon. Springfield, Thomas, 1969. 4. Sweet WH: Deafferentation pain after posterior rhizotomy, trauma to a limb, and herpes zoster. Neurosurgery 1984;15:928-932. 5. McFarland HR: Chronic traumatic trigeminal neuralgia. Southern Med J 1982;75:814-816. 6. LeBlanc JP, Epker BN: Serious alveolar nerve dysesthesia after endodontic procedure: report of three cases. J Am Dent Assoc 1984;108:605-607. 7. Hu JW, Dostrovsky JO, Lenz YE, Ball GJ, Sessle BJ: Tooth pulp deafferentation is associated with functional alterations in the properties of neurons in the trigeminal spinal tract nucleus. J Neurophysiol 1986;56:1650-1668. 8. Arvidson J, Gobel S: An HRp study of the central projections of primary trigeminal neurons which innervate tooth pulps in the cat. Brain Res 1981;210:1-16. 9. Nishimori T, Moskowitz M, Uhl GR: Opioid peptide gene expression in rat trigeminal nucleus caudalis neurons: normal distribution and effects of trigeminal deafferentation. J Comp Neurol 1988;274:142-150. 10. Nishimori T, Moskowitz M, Borosook D, Maciewicz R, Uhl G: Trigeminal and PAG modulation of opioid peptide gene expression in nucleus caudalis. Neurosci Abstr 1988;14:856. 11. Frazier CH, Russell EC: Neuralgia of the face: an analysis of 754 patients with relation to pain and other sensory phenomena before and after operation. Arch Neurol Psychiatry 1924;1 1:557-563. 12. Andres KH, von During M, Muszzynski K, Schmidt RF: Nerve fibers and their terminals of the dura mater encephali of the rat. Anat Embryol 1987;175:289-301. 13. Penfield W: Intracerebral vascular nerves. Arch Neurol Psychiatry 1940;27:30-44. 14. Moskowitz MA: Neurobiology of vascular head pain. 1984;16: 157-168. 15. Travell JG, Simons DG. Myofascial Pain and Dysfunction: The Trigger Point Manual. Baltimore, Williams and Wilkins, 1983. 16. Cervero F: Visceral nociception: peripheral and central aspects of visceral nociceptive systems. Phil Trans R Soc Lond B 1985;308:325-337. 17. Strassman A, Mason P, Moskowitz MA, Maciewicz R: Response of brainstem trigeminal neurons to electrical stimulation of the dura. Brain Res 1986;379:242-250. 18. Katayama Y, Watkins LR, Becker DP, Hates RL: Evidence for involvement of cholinoceptive cells of the parabrachial region in environmentally induced nociceptive suppression in the cat. Brain Res 1984;299:348-353. 19. Broton JG, Hu JW, Sessle BJ: Effects of temporomandibular joint stimulation on nociceptive and nonnociceptive neurons of the cat's trigeminal subnucleus caudalis (medullary dorsal horn). J neurophysiol 1988;59:1575-1589. 21. Sessle BJ, Hu JW, Amano N, Zhong G. Convergence of cutaneous, tooth pump, visceral, neck, and muscle afferents onto nociceptive and nonnociceptive neurons in trigeminal subnucleus caudalis (medullary dorsal horn) and its implications for referred pain. Pain 1986;27:219-235. 22. Sessle BJ, Hu JW, Amano N, Zhong G: Convergence of
132 Neurology of Facial Pain
cutaneous, tooth pulp, visceral, neck and muscle afferents onto nociceptive and non-nociceptive neurones in trigeminal subnucleus caudalis (medullary dorsal horn) and its implications for referred pain. Pain 1986;27:219-235. 23. Katayama Y, Tsubokawa T, Hirayama T, Yamamoto T:
Anesth Prog 37:129-132 1990
Pain relief following stimulation of the pontomescencephalic parabrachial region in humans: brain sites for nonopiate-mediated pain control. Appl Neurophysiol 1985;48:195-200. 24. Laskin DM. Etiology of the pain-dysfunction syndrome. J Am Dent Assoc 1969;79:154-160.
Neurologic Aspects of Chronic Facial Pain Raymond Maciewicz MD, PhD Associate Professor of Neurology and Neuroscience, Harvard Medical School, Boston, Massachusetts
Chronic facial pain can result from neuropathic changes associated with deafferentation. The pattern of deep afferent convergence on trigeminal cells may also relate to the pathophysiology of chronic facial pain disorders.
trigeminal rhizotomy, most of the facial skin and oral cavity are completely anesthetic. Only the most peripheral 2-3 cm of the facial skin is sensitive to noxious stimulation, although the evoked sensation is not pain. The peripheral face may therefore receive some afferent innervation from the 7th, 9th, and 10th cranial nerves as well as cervical nerves C2-C4. CHRONIC NEUROPATHIC FACIAL PAIN
A lthough there are many similarities in the organization of nociceptive transmission in the trigeminal and spinal systems, important differences between the two systems exist. Such differences may be important in the pathogenesis of certain forms of chronic facial pain, including deafferentation pain and chronic vascular face pain.
This difference in the peripheral branching pattern of trigeminal and spinal afferents may in part explain the common occurrence of neuropathic, deafferentation pain within the trigeminal system. Trigeminal nerve lesions are more frequently associated with posttraumatic dysesthesias than are spinal nerve injuries,4 and the conditions of anesthesia dolorosa and trigeminal neuralgia appear to be unique to the trigeminal system. A significant group of patients with chronic facial pain have a history of trauma to the trigeminal system that may be a source of chronic neuropathic facial pain.5 The disorder most frequently follows damage to the peripheral trigeminal branches, usually due to trauma or surgery. Posttraumatic trigeminal pain often involves the third division and the oral cavity, likely due to the frequency of oral pathology and dental surgery or extractions.6 Clinically, such patients usually have a clear history of nerve injury that preceeded the onset of pain. The pain is usually well localized to the distribution of the affected nerve. The pain usually consists of spontaneous dysesthesias and paresthesias superimposed on a more chronic, dull, aching pain. On examination, there is often evidence of a sensory loss in the region supplied by the injured nerve. This may be coupled with hypersensitivity to touch or pressure over the same area. Chronic mandibular pain in such patients is likely due to compression and neuroma formation in the involved trigeminal branches, because in some cases surgical decompression of the inferior alveolar nerve can provide substantial relief.6 However, central mechanisms may also play a role in posttraumatic facial pain. Sessle et a17 have demonstrated that simple endodontal pulpotomy in animals is associated with a reorganization and enlargement
TRIGEMINAL DISTRIBUTION
Following trigeminal root section, the insensate cutaneous region stretches from the vertex along midline to a point 1-2 cm below the chin. 1-3 Laterally, the trigeminal dermatome descends anteriorly from the vertex to the ear, across the zygoma, and down the cheek. Within the perioral region, the trigeminal dermatome includes the lips, teeth, gingiva, anterior 2/3 of the tongue, the palato-glossal fold, the uvula, and the soft palate. In addition to this cutaneous distribution, the trigeminal nerve contains afferents that provide the sensory innervation to a variety of deep tissues in the head, including the muscles of facial expression and mastication, the nasal and oral mucosae, the cornea, tongue, tooth pulp, dura mater, and external auditory meatus. In contrast to the spinal afferent system where there is significant overlap between adjacent sensory afferents, there is little functional overlap between the trigeminal dermatome and adjacent spinal or cranial nerves.2'3 After
Address correspondence to Raymond Maciewicz, MD, PhD, Spaulding Pain Rehabilitation Program, Spaulding Rehabilitation Hospital, Boston MA 02114. C 1990 by the American Dental Society of Anesthesiology
ISSN 0003-3006/90/$3.50
129
130
Neurology of Facial Pain
of the receptive fields of brainstem trigeminal neurons. Such physiologic changes may persist for months after surgery, and may be associated with anatomic evidence for degeneration and plastic reorganization in the trigeminal system following tooth extraction.8 Posterior trigeminal rhizotomy also results in persistent pain referred to the anesthetic zone of the face in approximately 10% of cases.4 Following rhizotomy, there is a loss of central trigeminal afferent terminals within the trigeminal complex, and deafferented central trigeminal neurons develop an irregular spontaneous discharge. Such cells also become less responsive to iontophoretically applied inhibitory transmitters, evidence that deafferentation likely produces a reorganization of central trigeminal circuitry. Recent data9'10 show that trigeminal rhizotomy in rats also results in a change in opiate gene expression within lamina I and II neurons, with an increase in cells that express preprodynorphin and a decrease in cells that express preproenkephalin. Such deafferentation-induced changes in gene expression may partly underlie the central reorganization of trigeminal neurons that results in deafferentation pain. As noted above, anesthesia dolorosa only occurs in 10% of patients undergoing rhizotomy; it is possible that genetically determined differences in the response of central neurons to deafferentation underlies the difference in response to deafferentation in individual cases. CHRONIC VASCULAR FACIAL PAIN
Many patients with chronic, recurrent facial pain have significant vasomotor and/or autonomic accompaniments to their pain, suggesting a vascular facial pain syndrome similar to migraine or cluster headache. As many as 50% of the patients in early series" had symptoms that included facial flushing, edema, unequal pupils, lacrimation, or nasal congestion; in some there were additional migranous symptoms of photophobia and nausea, as well as arterial tendemess during attacks. In these patients the pain is usually episodic, and predominantly one-sided; nausea and photophobia may accompany attacks. Between attacks the patient is free of pain. The episodic nature of the pain with long intervening pain-free periods suggests the diagnosis of a vascular pain syndrome, although in a significant group of patients the pain can become more chronic, with daily episodes of pain. The mechanism of pain in such conditions is likely due to activation of intracranial vascular nociceptors with referral of pain to the face. Most somatosensory research in the trigeminal system has focused on the innervation of the skin and specialized organs such as the teeth and eyes. However, most chronic, clinically relevant pain in the head usually involves afferents from deeper structures, such as muscles,
Anesth Prog 37:129-132 1990
joints, and major blood vessels, as well as the nasal sinuses and oral cavity. The sensory innervation of these structures largely arises from small caliber afferents, many of which contain neuropeptides. These afferents primarily serve a nociceptive function. Often, the pain evoked by activation of such deep afferents is referred to specific regions of the face and head. For example, the major cranial vessels that supply the brain and dura are innervated by small caliber peptidergic trigeminal sensory afferents.'2 Penfield'3 observed that mechanical or thermal stimulation of dural blood vessels in humans evokes pain. This pain is not felt locally; instead it is referred to a broad region of the first trigeminal division that usually includes the forehead and ipsilateral eye. Activation of vascular nociceptors with referral of pain to the forehead is a likely mechanism for many forms of cranial vascular pain, including the pain associated with certain forms of vascular headache. 4 Stimulation of other deep cranial afferents also causes referral of pain to the face. Specific structures may evoke characteristic patterns of referral. Noxious stimulation of the muscles of mastication, for example, can cause referral of pain to the maxilla, the orbit, or the teeth, depending on the site of stimulation. 15 The referral of deep cranial pain to distant sites on the face or scalp is analogous to the referral of other forms of visceral pain at spinal levels. 16 Deep sensory afferents from muscle, the temporomandibular joint capsule, or cranial blood vessels are primarily small caliber afferents that likely contribute a major projection to nucleus candalis (NC). These deep afferents terminate on brainstem trigeminal cells that often have nociceptive cutaneous receptive fields. The convergence of deep and cutaneous afferents onto the same cells likely accounts for the phenomenon of referred pain in the trigeminal system. Strassman et al,'7 for example, have shown that a population of wide dynamic range (WDR) and nociceptive specific (NS) cells in NC are excited by stimulation of major blood vessels in the dura. These same cells also receive a nociceptive input from the skin of the first trigeminal division, usually including the ipsilateral eye and forehead. This convergence of cutaneous and vascular afferents on the same cells in NC likely explains the common referral of cranial vascular pain to the forehead and eye. Such cells may mediate the pain associated with certain forms of vascular headache, including migraine. Cells in trigeminal nucleus caudalis that receive a convergent input from blood vessels and first division of the trigeminal nerve (V1) are located primarily in lamina V. Recent studies using intracellular injection techniques18 reveal that one population of these vascular convergence cells extensively collateralizes within the spinal trigeminal complex and the adjacent reticular formation. Within lamina V the terminals of these cells contain round synaptic
Anesth Prog 37:129-132 1990
vesicles and end on dendritic spines or shafts of other neurons in lamina V. Such cells are likely important modulators of trigeminal sensory transmission within the trigeminal complex itself. Because the synaptic morphology is consistent with excitatory neurotransmission, they may be responsible for exciting other lamina V neurons. This type of trigeminal neuron could in part explain the extensive cutaneous hypersensitivity that can follow a focal noxious stimulus applied to the face. A second population of vascular convergence cells have axons that project rostrally through the trigeminothalamic tract; these cells likely relay sensations of vascular pain that reach conscious perception. Some of these cells give rise to collateral projections that terminate in the nuclei of the dorsomedial medulla, including the nucleus of the solitary tract and the border of the vagal nucleus. Vascular facial pain syndromes are often associated with prominent autonomic features, including ipsilateral facial flushing, conjunctival injection, ptosis, myosis, and rhinorrhea, as well as systemic symptoms of bradycardia and hypertension. The collateral projections to the dorsomedial medulla of trigeminal vascular relay neurons may be important in the mediation of the local and systemic autonomic responses associated with vascular pain in the face and head. Afferents from other deep structures in the head, such as the temporomandibular joint,19 the cranial muscles,20-22 and the ethmoid sinus23 also converge on trigeminal cells with cutaneous receptive fields. The cutaneous receptive fields of such cells, however, are found in all three trigeminal dermatomes and include low threshold as well as nociceptive response patterns. The pattern of convergence for these deep afferents is therefore more variable than for cranial vascular inputs. It's likely, however, that the convergence of these deep afferents on cells with cutaneous receptive fields partly explains the referral of deep cranial pain to distant sites in the face and head. "5 The overlap of deep afferent inputs to brainstem trigeminal neurons may also be relevent in the pathophysiology of chronic myofascial pain that involves the masticatory muscles.24 Chronic facial pain of many types often becomes associated with masticatory muscle tendemess and restriction of movement. Convergence of deep afferents within the trigeminal system may play an important role in the development of this syndrome.
REFERENCES 1. Cushing H: The sensory distribution of the fifth cranial nerve. Bull John Hopkins Hosp 1904;15:213-232. 2. Denny-Brown D, Yanagisawa N: The function of the descending root of the fifth nerve. Brain 1973;96:783-814.
Maciewicz 131
3. White JC, Sweet WH: Pain and the Neurosurgeon. Springfield, Thomas, 1969. 4. Sweet WH: Deafferentation pain after posterior rhizotomy, trauma to a limb, and herpes zoster. Neurosurgery 1984;15:928-932. 5. McFarland HR: Chronic traumatic trigeminal neuralgia. Southern Med J 1982;75:814-816. 6. LeBlanc JP, Epker BN: Serious alveolar nerve dysesthesia after endodontic procedure: report of three cases. J Am Dent Assoc 1984;108:605-607. 7. Hu JW, Dostrovsky JO, Lenz YE, Ball GJ, Sessle BJ: Tooth pulp deafferentation is associated with functional alterations in the properties of neurons in the trigeminal spinal tract nucleus. J Neurophysiol 1986;56:1650-1668. 8. Arvidson J, Gobel S: An HRp study of the central projections of primary trigeminal neurons which innervate tooth pulps in the cat. Brain Res 1981;210:1-16. 9. Nishimori T, Moskowitz M, Uhl GR: Opioid peptide gene expression in rat trigeminal nucleus caudalis neurons: normal distribution and effects of trigeminal deafferentation. J Comp Neurol 1988;274:142-150. 10. Nishimori T, Moskowitz M, Borosook D, Maciewicz R, Uhl G: Trigeminal and PAG modulation of opioid peptide gene expression in nucleus caudalis. Neurosci Abstr 1988;14:856. 11. Frazier CH, Russell EC: Neuralgia of the face: an analysis of 754 patients with relation to pain and other sensory phenomena before and after operation. Arch Neurol Psychiatry 1924;1 1:557-563. 12. Andres KH, von During M, Muszzynski K, Schmidt RF: Nerve fibers and their terminals of the dura mater encephali of the rat. Anat Embryol 1987;175:289-301. 13. Penfield W: Intracerebral vascular nerves. Arch Neurol Psychiatry 1940;27:30-44. 14. Moskowitz MA: Neurobiology of vascular head pain. 1984;16: 157-168. 15. Travell JG, Simons DG. Myofascial Pain and Dysfunction: The Trigger Point Manual. Baltimore, Williams and Wilkins, 1983. 16. Cervero F: Visceral nociception: peripheral and central aspects of visceral nociceptive systems. Phil Trans R Soc Lond B 1985;308:325-337. 17. Strassman A, Mason P, Moskowitz MA, Maciewicz R: Response of brainstem trigeminal neurons to electrical stimulation of the dura. Brain Res 1986;379:242-250. 18. Katayama Y, Watkins LR, Becker DP, Hates RL: Evidence for involvement of cholinoceptive cells of the parabrachial region in environmentally induced nociceptive suppression in the cat. Brain Res 1984;299:348-353. 19. Broton JG, Hu JW, Sessle BJ: Effects of temporomandibular joint stimulation on nociceptive and nonnociceptive neurons of the cat's trigeminal subnucleus caudalis (medullary dorsal horn). J neurophysiol 1988;59:1575-1589. 21. Sessle BJ, Hu JW, Amano N, Zhong G. Convergence of cutaneous, tooth pump, visceral, neck, and muscle afferents onto nociceptive and nonnociceptive neurons in trigeminal subnucleus caudalis (medullary dorsal horn) and its implications for referred pain. Pain 1986;27:219-235. 22. Sessle BJ, Hu JW, Amano N, Zhong G: Convergence of
132 Neurology of Facial Pain
cutaneous, tooth pulp, visceral, neck and muscle afferents onto nociceptive and non-nociceptive neurones in trigeminal subnucleus caudalis (medullary dorsal horn) and its implications for referred pain. Pain 1986;27:219-235. 23. Katayama Y, Tsubokawa T, Hirayama T, Yamamoto T:
Anesth Prog 37:129-132 1990
Pain relief following stimulation of the pontomescencephalic parabrachial region in humans: brain sites for nonopiate-mediated pain control. Appl Neurophysiol 1985;48:195-200. 24. Laskin DM. Etiology of the pain-dysfunction syndrome. J Am Dent Assoc 1969;79:154-160.
