Abstract
A rat model of chronic parotitis was developed following a direct injection of Complete Freund's adjuvant (CFA) into the unilateral parotid gland via the parotid duct without skin incision. The nocifensive behavior, plasma extravasation in the parotid gland, and trigeminal Fos protein expression, a marker of neuronal activation, were analyzed in this model and compared to that of the saline-injected rats. A significant reduction of the escape threshold to mechanical stimulation of the lateral face on the ipsilateral side to the CFA injection was observed at 1–6 days after CFA injection as compared to that of the pre-CFA control (P<0.01). The lateral face region contralateral to the CFA injection also showed mechanical hyperalgesia at 1–6 days after injection (P<0.05). The plasma extravasation was significantly increased in the parotid gland ipsilateral to CFA injection as compared to that of the parotid gland with saline injection at 3 days after injection as shown by Evans' blue dye extravasation (P<0.05). Bilateral expression of Fos protein-like immunoreactive cells was observed in the transition zone between the trigeminal spinal nucleus interpolaris (Vi) and caudalis (Vc) and paratrigeminal nucleus (Pa5). On the other hand, a significant unilateral expression of Fos protein-positive cells was observed on the ipsilateral side of the upper cervical (C2) dorsal horn (P<0.05). This model of parotitis can be used to study trigeminal pain mechanisms associated with sialadenitis. A unique feature of this preparation is that the inflammation was limited to the parotid gland after intraductal injection of CFA, allowing analysis of peripheral input from a defined orofacial region. The model will be useful in developing new strategies to treat chronic orofacial pain.
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Abbreviations
- NTS :
-
Nucleus tractus solitarius
- ECu :
-
External cuneate nucleus
- CFA :
-
Complete Freund's adjuvant
- Cu :
-
Cuneate nucleus
- Gr :
-
Gracile nucleus
- IO :
-
Inferior olivary nucleus
- LI :
-
Like-immunoreactivity
- mlf :
-
Medial longitudinal fasciculus
- Pa5 :
-
Paratrigeminal nucleus
- PBS :
-
Phosphate-buffered saline
- PG :
-
Parotid gland
- Py :
-
Pyramidal tract
- RVL :
-
Rostroventrolateral reticular nucleus
- sol :
-
Solitary tract
- sp5 :
-
Spinal trigeminal tract
- Vi :
-
Subnucleus interpolaris of the spinal trigeminal nucleus
- Vc :
-
Subnucleus caudalis of the spinal trigeminal nucleus
- TB :
-
Tris buffer
- TMJ :
-
Temporomandibular joint
- Vi/Vc :
-
Trigeminal subnucleus interpolaris/subnucleus caudalis
References
Abbadie C, Besson JM (1992) C-fos expression in rat lumbar spinal cord during the development of adjuvant-induced arthritis. Neurosci 48:985-993
Abbadie C, Lombard M-C, Morain F, Besson JM (1992) Fos-like immunoreactivity in the rat superficial dorsal horn induced by Formalin injection in the forepaw: effects of dorsal rhizotomies. Brain Res 578:17–25
Armstrong CL, Hopkins DA (1998) Neurochemical organization of paratrigeminal nucleus projections to the dorsal vagal complex in the rat. Brain Res 785:49–57
Bereiter DA, Hathaway CB, Benetti AP (1994) Caudal portions of the spinal trigeminal complex are necessary for autonomic responses and display Fos-like immunoreactivity after corneal stimulation in the cat. Brain Res 657:73–82
Bereiter DA, Bereiter DF, Ramos M (2002) Vagotomy prevents morphine-induced reduction in Fos-like immunoreactivity in trigeminal spinal nucleus produced after TMJ injury in a sex-dependent manner. Pain 96:205–213
Boss JH, Sela J, Bab JA, Dishon T, Rosenmann E (1976) Experimental allergic sialoadenitis. IX. The regional lymph nodes after antigenic challenges of the parotid glands in rats. Pathol Eur 11:231-237
Bossut DF, Maixner W (1996) Effects of cardiac vagal afferent electro stimulation on the responses of trigeminal and trigeminothalamic neurons to noxious orofacial stimulation. Pain 65:101-109
Bullitt E (1990) Expression of c-fos-like protein as a marker for neuronal activity following noxious stimulation in the rat. J Comp Neurol 296:517-530
Bullitt E (1991) Somatotopy of spinal nociceptive processing. J Comp Neurol 312:279-290
Capra NF, Dessem D (1992) Central connections of trigeminal primary afferent neurons: Topographical and functional considerations. Cr Rev Oral Biol Med. 4:1–52
Chan-Palay V (1978) The paratrigeminal nucleus. I. Neurons and synaptic organization. J Neurocytol 7:405–418
Coderre TJ, Katz J, Vaccarino AL, Melzack R (1993) Contribution of central neuroplasticity to pathological pain: review of clinical and experimental evidence. Pain 52:259-285
Ekstrom J, Ekman R, Hakanson R, Sjogren S, Sundler F (1988) Calcitonin gene-related peptide in rat salivary glands: neuronal localization, depletion upon nerve stimulation, and effects on salivation in relation to substance P. Neuroscience 26:933-949
Ekstrom J, Asztely A, Tobin G (1996) Non-adrenergic, non-cholinergic influences on parotid acinar degranulation in response to stimulation of the parasympathetic innervation in the anaesthetized rat. Exp Physiol 81:935-942
Greene EC (1955) Anatomy of the rat. Hafner, New York
Hathaway CB, Hu JW, Bereiter D (1995) Distribution of Fos-like immunoreactivity in the caudal brainstem of the rat following noxious chemical stimulation of the temporomandibular joint. J Comp Neurol 356:444-456
Hebel R, Stromberg MW (1986) Anatomy and Embryology of the Laboratory Rat. BioMed Verlag, Wörthsee
Hunt SP, Pini A, Evan G (1987) Induction of c-fos-like protein in spinal cord neurons following sensory stimulation. Nature 328:632-634
Imbe H, Dubner R, Ren K (1999) Masseteric inflammation-induced Fos protein expression in the trigeminal interpolaris/caudalis transition zone: contribution of somatosensory-vagal-adrenal integration. Brain Res 845:165–175
Iwata K, Takahashi O, Tsuboi Y, Ochiai H, Hibiya J, Sakaki T, Yamaguchi Y, Sumino R (1998) Fos protein induction in the medullary dorsal horn and first segment of the spinal cord by tooth-pulp stimulation in cats. Pain 75:27–36
Iwata K, Tashiro A, Tsuboi Y, Imai T, Sumino R, Morimoto T, Dubner R, Ren K (1999) Medullary dorsal horn neuronal activity in rats with persistent temporomandibular joint and perioral inflammation. J Neurophysiol 82:1244-1253
Keay KA, Clement CI, Owler B, Depaulis A, Bandler R (1994) Convergence of deep somatic and visceral nociceptive information onto a discrete ventrolateral midbrain periaqueductal gray region. Neuroscience 61:727-732
Kerr FWL (1963) The divisional organization of afferent fibers of the trigeminal nerve. Brain 86:721–732
Leipzig B, Obert P (1979) Parotid gland swelling. J Fam Pract 9:1085–1093
Menetrey D, Gannon A, Levine JD, Basbaum AI (1989) Expression of c-fos protein in interneurons and projection neurons of the rat spinal cord in response to noxious somatic, articular, and visceral stimulation. J Comp Neurol 85:177-195
Nomura H, Ogawa A, Tashiro A, Morimoto T, Hu JW, Iwata K (2002) Induction of Fos protein-like immunoreactivity in the trigeminal spinal nucleus caudalis and upper cervical cord following noxious and non-noxious mechanical stimulation of the whisker pad of the rat with an inferior alveolar nerve transection. Pain 95:225–238
Nozaki H, Harasawa A, Hara H, Kohno A, Shigeta A (1994) Ultrasonographic features of recurrent parotitis in childhood. Pediatr Radiol 24:98–100
Orser B (1990) Facial pain in the recovery room secondary to acute parotitis. Anesthesiology 72:1090-1091
Park JW (1992) Recurrent parotitis in childhood. Clin Pediatr 31:254–55
Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates. 4th ed. Academic, New York.
Phelan KD, Falls WM (1989) The interstitial system of the spinal trigeminal tract in the rat: Anatomical evidence for morphological and functional heterogeneity. Somatos Mot Res 6:367–399
Pozo MA, Cervero F (1993) Neurons in the rat spinal trigeminal complex driven by corneal nociceptors: receptive-field properties and effects of noxious stimulation of the cornea. J Neurophysiol 70:2370–2378
Presley RW, Menetrey D, Levine JD, Basbaum AI (1990) Systemic morphine suppresses noxious stimulus-evoked Fos protein-like immunoreactivity in the rat spinal cord. J Neurosci 10:323-335
Ren K (1999) An improved method for assessing mechanical allodynia in the rat. Physiol Beh 67:711–716
Ren K, Dubner R (1999) Central Nervous System Plasticity and Persistent Pain. J Orofacial Pain 13:155–163
Saxon DW, Hopkins DA (1998) Efferent and collateral organization of paratrigeminal nucleus projections: an anterograde and retrograde fluorescent tracer study in the rat. J Comp Neurol 402:93–110
Sharkey KA, Templeton D (1984) Substance P in the rat parotid gland: evidence for a dual origin from the otic and trigeminal ganglia. Brain Res 304:392-396
Stanley RB, Fernandez JA, Peppard SB (1983) Cervicofacial mycobacterial infections presenting as major salivary gland disease. Laryngoscope 93:1271-1275
Strassman AM, Vos BP (1993) Somatotopic and laminar organization of fos-like immunoreactivity in the medullary and upper cervical dorsal horn induced by noxious facial stimulation in the rat. J Comp Neurol 331:495–516
Sugimoto T, Hara T, Shirai H, Abe T, Ichikawa H, Sato T (1994) c-fos induction in the subnucleus caudalis following noxious mechanical stimulation of the oral mucous membrane. Exp Neurol 129:251-256
Takemura M, Sugimoto T, Sakai A (1987) Topographic organization of central terminal region of different sensory branches of the rat mandibular nerve. Exp Neurol 96:540–557
Tobin G (1998) Presynaptic muscarinic M1 and M2 receptor modulation of auriculotemporal nerve transmission in the rat. J Auton Nerv Syst 72:61–71
Tolle TR, Castro-Lopes JM, Coimbra A, Zieglgansberger W (1990) Opiates modify induction of c-fos proto-oncogene in the spinal cord of the rat following noxious stimulation. Neurosci Lett 111:46–51
Vasama JP (2000) Tympanic neurectomy and chronic parotitis. Acta Otolaryngol 120:995-998
Watkin GT, Hobsley M (1986) Natural history of patients with recurrent parotitis and punctate sialectasis. Br J Surg 73:745-748
Williams S, Evan GI, Hunt, SP (1990) Changing patterns of c-fos induction in spinal neurons following thermal cutaneous stimulation in the rat. Neurosci 36:73–81
Zhou Q, Imbe H, Dubner R, Ren K (1999) Persistent Fos protein expression after orofacial deep or cutaneous tissue inflammation in rats: implications for persistent orofacial pain. J Comp Neurol 412:276-291
Zimmerman M (1983) Ethical guidelines for investigation of experimental pain in conscious animals. Pain 16:109-110
Zohar Y, Siegal A, Siegal G, Halpern M, Levy B, Gal R (2002) The great auricular nerve; does it penetrate the parotid gland? An anatomical and microscopical study. J Craniomaxillofac Surg 30:318–321
Acknowledgements
This study was supported by Grants-in-Aid for Scientific Research (14571761) from the Japanese Ministry of Education, Science and Culture, a grant from the Ministry of Education, Culture, Sports, Science, and Technology to promote multi-disciplinary research projects, the Sato and Uemura Funds, Nihon University School of Dentistry, and the NIH grant DE11964 (K.R.).
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Ogawa, A., Ren, K., Tsuboi, Y. et al. A new model of experimental parotitis in rats and its implication for trigeminal nociception. Exp Brain Res 152, 307–316 (2003). https://doi.org/10.1007/s00221-003-1538-x
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DOI: https://doi.org/10.1007/s00221-003-1538-x