Orthodontic tooth movement is known to cause pain and discomfort to patients. Mechanically induced inflammatory responses in the periodontium are assumed to be related to the mechanism of pain sensation. An immediate-early gene, c-fos, that is expressed within some neurons following synaptic activation, is widely used as a marker for neuronal activity following noxious or innocuous stimulation. We have recently demonstrated that experimental tooth movement produced Fos induction in the ipsilateral trigeminal subnucleus caudalis and in the bilateral lateral parabrachial nucleus, which is known to be involved in the transmission of nociceptive information. As a further step, we investigated the distribution of Fos-like immunoreactive neurons in the upper brain regions. Twenty-four hours after the commencement of the experimental tooth movement, the Fos-like immunoreactive neurons appeared in the central nucleus of the amygdala (Ce), paraventricular nucleus of the hypothalamus (PVH), and paraventricular nucleus of the thalamus (PV) of the experimental rats. The numbers of the labeled neurons were significantly increased by 639% (P < 0.001) and 644% (P < 0.001) in the ipsilateral and contralateral sides of the Ce, respectively, by 292% (P < 0.001) and 307% (P < 0.001) in the ipsilateral and contralateral sides of the PVH, and by 264% (P < 0.0001) in the PV with respect to sham control rats. These results suggest that nociceptive information caused by experimental tooth movement might be transmitted and modulated in several regions of the forebrain.
Alden M., Besson JM, Bernard JF (1994). Organization of the efferent projections from the pontine parabrachial area to the bed nucleus of the stria terminalis and neighboring regions: a PHA-L study in the rat. J Comp Neurol341 :289-314.
2.
Barnett EM, Evans GD, Sun N., Perlman S., Cassell MD (1995). Anterograde tracing of trigeminal afferent pathways from the murine tooth pulp to cortex using herpes simplex virus type 1. J Neurosci15:2972-2984.
3.
Bernard JF, Huang GF, Besson JM (1990). Effect of noxious somesthetic stimulation on the activity of neurons of the nucleus centralis of the amygdala. Brain Res523:347-350.
4.
Bernard JF, Huang GF, Besson JM (1992). Nucleus centralis of the amygdala and the globus pallidus ventralis: electrophysiological evidence for an involvement in pain processes. J Neurophysiol68:551-569.
5.
Bernard JF, Huang GF, Besson JM (1994). The parabrachial area: electrophysiological evidence for an involvement in visceral nociceptive processes. J Neurophysiol71:1646-1660.
6.
Bester H., Menendez L., Besson JM, Bernard JF (1995). Spino (trigemino) parabrachiohypothalamic pathway: electrophysiological evidence for an involvement in pain processes. J Neurophysiol73:568-585.
7.
Brown DF, Moerenhout RG (1991). The pain experience and psychological adjustment to orthodontic treatment of preadolescents, adolescents, and adults. Am J Orthod Dentofac Orthop100:349-356.
8.
Bullitt E. (1990). Expression of c-fos-like protein as a marker for neuronal activity following noxious stimulation in the rat. J Comp Neurol296:517-530.
9.
Coimbra F., Coimbra A. (1994). Dental noxious input reaches the subnucleus caudalis of the trigeminal complex in the rat, as shown by c-fos expression upon thermal or mechanical stimulation. Neurosci Lett173:201-204.
10.
Dawson NJ, Hellon RF, Hubbard JI (1980). Cell responses evoked by tooth pulp stimulation above the marginal layer of the cat's trigeminal nucleus caudalis. J Comp Neurol193:983-994.
11.
Ding YQ, Takada M., Shigemoto R., Mizumo N. (1995). Spino-parabrachial tract neurons showing substance P receptor-like immunoreactivity in the lumbar spinal cord of the rat. Brain Res674:336-340.
12.
Dragunow M., Faull R. (1989). The use of c-fos as a metabolic marker in neuronal pathway tracing. J Neurosci Meth29:261-265.
13.
Ferreira SH, Nakamura M., de Abreu Castro MS (1978). The hyperalgesic effects of prostacyclin and prostaglandin E2. Prostaglandins16:31-37.
14.
Grieve WG 3rd, Johnson GK, Moore RN, Reinhardt RA, DuBois LM (1994). Prostaglandin E (PGE) and interleukin-1 beta (IL-1 beta) levels in gingival crevicular fluid during human orthodontic tooth movement . Am J Orthod Dentofac Orthop105:369-374.
15.
Helmstetter FJ, Bellgowan PS (1993). Lesions of the amygdala block conditional hypoalgesia on the tail flick test. Brain Res612:253-257.
16.
Hu JW, Sessle BJ (1984). Comparison of responses of cutaneous nociceptive and nonnociceptive brain stem neurons in trigeminal subnucleus caudalis (medullary dorsal horn) and subnucleus oralis to natural and electrical stimulation of tooth pulp. J Neurophysiol52:39-53.
17.
Hylden JL, Anton F., Nahin RL (1989). Spinal lamina I projection neurons in the rat: collateral innervation of parabrachial area and thalamus. Neuroscience28:27-37.
18.
Kato J., Wakisaka S., Tabata M., Sasaki Y., Kurisu K. (1994). Induction of Fos protein in rat trigeminal nucleus complex during an experimental tooth movement. Arch Oral Biol35:723-726.
19.
Kess B., Zwilling B., Shanfeld J., Davidovitch Z. (1987). The effect of indomethacin on periodontal PGE content during orthodontic treatment (abstract). J Dent Res66:332.
20.
Ma W., Peschanski M. (1988). Spinal and trigeminal projections to the parabrachial nucleus in the rat: electron-microscopic evidence of a spino-ponto-amygdalian somatosensory pathway. Somatosens Res5:247-257.
21.
Manning BH, Mayer DJ (1995). The central nucleus of the amygdala contributes to the production of morphine antinociception in the formalin test. Pain63:141-152.
22.
Matsumoto N., Kawarada K., Kamata K., Suzuki TA (1993). Electrical stimulation of tooth pulp increases the expression of c-fos in the cat supraoptic nucleus but not in the paraventricular nucleus. Life Sci53:1235-1241.
23.
McKitrick DJ, Calaresu FR (1993). Expression of Fos in rat central nervous system elicited by afferent stimulation of the femoral nerve. Brain Res632:127-135.
24.
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 Neurol285:177-195.
25.
Morgan JI, Cohen DR, Hempstead JL, Curran T. (1987). Mapping patterns of c-fos expression in the central nervous system after seizure. Science237:192-197.
26.
Ngan P., Kess B., Wilson S. (1989). Perception of discomfort by patients undergoing orthodontic treatment. Am J Orthod Dentofac Orthop96:47-53.
27.
Paxinos G., Watson C. (1986). The rat brain in stereotaxic coordinates. 2nd rev. ed. Sydney: Academic Press.
28.
Sagar SM, Sharp FR, Curran T. (1988). Expression of c-fos protein in brain: metabolic mapping at the cellular level. Science240:1328-1331.
29.
Saito M., Saito S., Ngan PW, Shanfeld J., Davidovitch Z. (1991). Interleukin 1 beta and prostaglandin E are involved in the response of periodontal cells to mechanical stress in vivo and in vitro . Am J Orthod Dentofac Orthop99:226-240.
30.
Senba E., Matsunaga K., Tohyama M., Noguchi K. (1993). Stress-induced c-fos expression in the rat brain: activation mechanism of sympathetic pathway. Brain Res Bull31:329-344.
31.
Slugg RM, Light AR (1994). Spinal cord and trigeminal projections to the pontine parabrachial region in the rat as demonstrated with Phaseolus vulgaris leucoagglutinin. J Comp Neurol339:49-61.
32.
Storey E. (1973). The nature of tooth movement. Am J Orthod63:292-314.
33.
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 Neurol129:251-256.
34.
Turner BH, Herkenham M. (1991). Thalamoamygdaloid projections in the rat: a test of the amygdala's role in sensory processing. J Comp Neurol313:295-325.
35.
Waldo CM, Rothblatt JM (1954). Histological responses to tooth movement in the laboratory rat. Procedure and preliminary observations. J Dent Res33:481-486.
36.
Wang LG, Li HM, Li JS (1994). Formalin induced Fos-like immunoreactive neurons in the trigeminal spinal caudal subnucleus project to contralateral parabrachial nucleus in the rat. Brain Res649:62-70.
37.
Yamashiro T., Nakagawa K., Satoh K., Moriyama H., Takada K. (1997). c-fos expression in the trigeminal sensory complex and pontine parabrachial areas following experimental tooth movement. Neuroreport8:2351-2353.
