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ABSTRACT: Abnormal sensitivity to bright light can cause discomfort or pain and evoke protective reflexes such as lacrimation. Although the trigeminal nerve is probably involved, the mechanism linking luminance to somatic sensory nerve activity remains uncertain. This study determined the effect of bright light on second-order ocular neurons at the ventral trigeminal interpolaris/caudalis transition (Vi/Vc) region, a major termination zone for trigeminal sensory fibers that innervate the eye. Most Vi/Vc neurons (80.9%) identified by responses to mechanical stimulation of the ocular surface also encoded bright light intensity. Light-evoked neural activity displayed a long latency to activation (> 10 s) and required transmission through the trigeminal root ganglion. Light-evoked neural activity was inhibited by intravitreal injection of phenylephrine or l-N(G) -nitro-arginine methyl ester (L-NAME), suggesting a mechanism coupled to vascular events within the eye. Laser Doppler flowmetry revealed rapid light-evoked increases in ocular blood flow that occurred prior to the increase in Vi/Vc neural activity. Synaptic blockade of the Vi/Vc region by cobalt chloride prevented light-evoked increases in tear volume, whereas blockade at the more caudal spinomedullary junction (Vc/C1) had no effect. In summary, Vi/Vc neurons encoded bright light intensity and were inhibited by drugs that alter blood flow to the eye. These results support the hypothesis that light-responsive neurons at the Vi/Vc transition region are critical for ocular-specific functions such as reflex lacrimation, whereas neurons at the caudal Vc/C1 junction region probably serve other aspects of ocular nociception.
European Journal of Neuroscience 09/2012; · 3.63 Impact Factor
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ABSTRACT: Psychological stress is a risk factor for the development of musculoskeletal pain of the head and neck; however, the basis for this relationship remains uncertain. This study tested the hypothesis that psychophysical stress alone was sufficient to alter the encoding properties of spinomedullary dorsal horn neurons and masseter muscle activity in male rats. Repeated forced swim conditioning increased markedly both the background firing rate and temporomandibular joint (TMJ)-evoked activity of neurons in deep dorsal horn, while neurons in superficial laminae were less affected. Stress also increased the responses to stimulation of facial skin overlying the TMJ of neurons in deep and superficial dorsal horn. TMJ-evoked masseter muscle activity was enhanced significantly in stressed rats, an effect that was reduced by prior blockade of the spinomedullary junction region. These data indicated that repeated psychophysical stress induced widespread effects on the properties of medullary dorsal horn neurons and masseter muscle activity. The effects of stress were seen preferentially on neurons in deep dorsal horn and included enhanced responses to chemosensory input from the TMJ and mechanical input from overlying facial skin. The stress-induced elevation in TMJ-evoked masseter muscle activity matched well with the changes seen in dorsal horn neurons. It is concluded that the spinomedullary junction region plays a critical role in the integration of psychophysical stress and sensory information relevant for nociception involving deep craniofacial tissues.
European Journal of Neuroscience 04/2012; 36(1):2025-34. · 3.63 Impact Factor
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Pain 03/2010; 148(3):519; author reply 519-20. · 5.78 Impact Factor
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ABSTRACT: Bright light can cause ocular discomfort and/or pain; however, the mechanism linking luminance to trigeminal nerve activity is not known. In this study we identify a novel reflex circuit necessary for bright light to excite nociceptive neurons in superficial laminae of trigeminal subnucleus caudalis (Vc/C1). Vc/C1 neurons encoded light intensity and displayed a long delay (>10s) for activation. Microinjection of lidocaine into the eye or trigeminal root ganglion (TRG) inhibited light responses completely, whereas topical application onto the ocular surface had no effect. These findings indicated that light-evoked Vc/C1 activity was mediated by an intraocular mechanism and transmission through the TRG. Disrupting local vasomotor activity by intraocular microinjection of the vasoconstrictive agents, norepinephrine or phenylephrine, blocked light-evoked neural activity, whereas ocular surface or intra-TRG microinjection of norepinephrine had no effect. Pupillary muscle activity did not contribute since light-evoked responses were not altered by atropine. Microinjection of lidocaine into the superior salivatory nucleus diminished light-evoked Vc/C1 activity and lacrimation suggesting that increased parasympathetic outflow was critical for light-evoked responses. The reflex circuit also required input through accessory visual pathways since both Vc/C1 activity and lacrimation were prevented by local blockade of the olivary pretectal nucleus. These findings support the hypothesis that bright light activates trigeminal nerve activity through an intraocular mechanism driven by a luminance-responsive circuit and increased parasympathetic outflow to the eye.
Pain 03/2010; 149(2):235-42. · 5.78 Impact Factor
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ABSTRACT: Endotoxin-induced uveitis (EIU) is commonly used in animals to mimic ocular inflammation in humans. Although the peripheral aspects of EIU have been well studied, little is known of the central neural effects of anterior eye inflammation. EIU was induced in male rats by endotoxin or lipopolysaccharide (LPS, 1 mg/kg ip) given 2 or 7 days earlier. Neurons responsive to mechanical stimulation of the ocular surface were recorded under barbiturate anesthesia at the trigeminal subnucleus interpolaris/caudalis (Vi/Vc) transition and subnucleus caudalis/cervical cord (Vc/C1) junction, the main terminal regions for corneal nociceptors. Two days after LPS, Vc/C1 units had reduced responses to histamine, nicotine, and CO(2) gas applied to the ocular surface, whereas unit responses were increased 7 days after LPS. Those units with convergent cutaneous receptive fields at Vc/C1 were enlarged 7 days after LPS. Units at the Vi/Vc transition also had reduced responses to histamine and CO(2) 2 days after LPS but no enhancement was seen at 7 days. Tear volume evoked by CO(2) was reduced 2 days after LPS and returned toward control values by 7 days, whereas CO(2)-evoked eye blinks were normal at 2 days and increased 7 days after LPS. These results indicate that a single exposure to endotoxin causes long-term changes in the excitability of second-order neurons responsive to noxious ocular stimulation. The differential effects of EIU on tear volume and eye blink lend further support for the hypothesis that ocular-sensitive neurons at the Vi/Vc transition and Vc/C1 junction regions mediate different aspects of pain during intraocular inflammation.
Journal of Neurophysiology 01/2006; 94(6):3815-25. · 3.32 Impact Factor
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ABSTRACT: The role of peripheral 5HT3 receptors in the orofacial nocifensive behavior induced by the injection of formalin into masseter muscle was evaluated. The behavioral activities evoked by the formalin injection exhibited a biphasic response in the rats with or without temporomandibular joint (TMJ) inflammation (CFA group or non-CFA group). The orofacial nocifensive behavioral activity was enhanced after TMJ inflammation. Systemic administration of tropisetron, 5HT3 receptor antagonist, reduced the nocifensive behavioral activities in the late phase of orofacial formalin test in CFA group, but not in non-CFA group. Local administration of tropisetron into the masseter muscle in CFA group, but not in non-CFA group also attenuated the behavioral activities in the late phase. Unexpectedly, low dose of local tropisetron reduced the nocifensive behavioral activities in the early phase of orofacial formalin test in CFA group. These data suggest that induction of TMJ inflammation causes the elevation of the orofacial nocifensive behavioral activities evoked by formalin injection into masseter muscle, and that peripheral 5HT3 receptors may play a critical role in nociception and the transmission of orofacial pain.
Neuroscience Letters 10/2004; 367(2):259-63. · 2.11 Impact Factor
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ABSTRACT: Reflex tears are produced by many conditions, one of which is drying of the ocular surface. Although peripheral neural control of the lacrimal gland is well established, the afferent pathways and properties of central premotor neurons necessary for this reflex are not known. Male rats under barbiturate anesthesia were used to determine whether neurons at the ventral trigeminal subnucleus interpolaris- caudalis (Vi/Vc) transition or the trigeminal subnucleus caudalis-cervical cord (Vc/C1) junction region in the lower brainstem were necessary for tears evoked by noxious chemical stimulation (CO2 pulses) or drying of the ocular surface. Both the Vi/Vc transition and Vc/C1 junction regions receive a dense direct projection from corneal nociceptors. Synaptic blockade of the Vi/Vc transition, but not the Vc/C1 junction, by the GABA(A) receptor agonist muscimol inhibited CO2-evoked tears. Glutamate excitation of the Vi/Vc transition, but not the Vc/C1 junction, increased tear volume. Single units recorded at the Vi/Vc transition, but not at the Vc/C1 junction, were inhibited by wetting and excited by drying the ocular surface. Nearly all moisture-sensitive Vi/Vc units displayed an initial inhibitory phase to noxious concentrations of CO2 followed by delayed excitation and displayed an inhibitory surround receptive field from periorbital facial skin. Drying of the ocular surface produced many Fos-positive neurons at the Vi/Vc transition, but not at the Vc/C1 junction. This is the first report of a unique class of moisture-sensitive neurons that exist only at the ventral Vi/Vc transition, and not at more caudal portions of Vc, that may underlie fluid homeostasis of the ocular surface.
Journal of Neuroscience 05/2004; 24(17):4224-32. · 7.11 Impact Factor
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ABSTRACT: After transection of the inferior alveolar nerve (IAN: the third branch of the trigeminal nerve), the whisker pad area, which is innervated by the second branch of the trigeminal nerve, showed hypersensitivity to mechanical stimulation. Two days after IAN transection, the threshold intensity for escape behavior to mechanical stimulation of the ipsilateral whisker pad area was less than 1.0 g, a sign of allodynia, and returned to the preoperative level (preoperative threshold: 52.0 g) at 32 days after surgery. This decrement of escape threshold lasted for more than 3 weeks. The whisker pad area contralateral to the IAN transection also showed a decrease in escape threshold to non-noxious mechanical stimulation as compared with sham-operated rats. However, the change in threshold intensity for the side contralateral to transection was not as pronounced as that on the ipsilateral side. Fos protein-like immunoreactive (LI) cells were observed in the superficial laminae but not dominant in deeper laminae of the trigeminal spinal nucleus caudalis (Vc) and the first segment of the spinal cord (C1) after non-noxious mechanical stimulation of the whisker pad area in the rats with IAN transection. Fos protein-LI cells were expressed bilaterally in the Vc and C1, but were more numerous on the ipsilateral side to transection than on the contralateral side. The largest number of Fos protein-LI cells was observed at 2400 microm caudal from the trigeminal subnucleus interporalis (Vi)-Vc border both in ipsilateral and contralateral sides. The number of Fos protein-LI cells increased after application of 1, 4, and 16 g stimuli as compared to rats without mechanical stimulation. Furthermore, an extensively greater number of Fos protein-LI cells were expressed both in superficial and deep laminae of the bilateral Vc and C1 of the spinal cord after subcutaneous injection of mustard oil into the whisker pad. Fos protein expression after mustard oil injection was much stronger than that observed after any mechanical stimulation in the rats with IAN transection. These data suggest that the change in the numbers and spatial arrangement of nociceptive neurons in the Vc and C1 after IAN transection reflect the development of mechanical hyperalgesia in the area adjacent to the IAN innervated region.
Pain 03/2002; 95(3):225-38. · 5.78 Impact Factor
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ABSTRACT: To understand characteristics of the pain system in the elderly, we investigated the electrophysiological properties of nociceptive neurons in the lumbar spinal dorsal horn of aged (29-34-mo old) and adult (7-13-mo old) rats. The responses of nociceptive neurons to noxious thermal stimulation, as well as the spontaneous firing rate, were significantly higher in the aged as compared with adult rats. Furthermore, the size of the high-threshold receptive field area of wide dynamic range neurons was larger (P < 0.01) and that of the low-threshold area was smaller (P < 0.05) in aged rats than in adult rats. The increased nociceptive neuronal activity in the aged rats correlated with the finding that the paw withdrawal latency was significantly shorter in the aged rats than those of the adult rats following heat stimulation of the hind paw (P < 0.05). Reversible local anesthetic block of descending pathways resulted in a dramatic increase in neuronal activity in adult rats but had little effect in aged rats. There was also a significant loss of serotoninergic and noradrenergic fibers in the spinal dorsal horn of the aged rats. These results demonstrate an age-related plasticity in spinal nociceptive processing that is related to impairment of descending modulatory pathways.
Journal of Neurophysiology 02/2002; 87(2):1086-93. · 3.32 Impact Factor
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ABSTRACT: In order to clarify the functional role of glutamate receptors of the gracile nucleus neurons in rats with nerve injury-induced hyperalgesia, pharmacological, electrophysiological and in situ hybridization techniques were used in rats with chronic constriction nerve injury (CCI) of the sciatic nerve. A total of 54 wide dynamic range neurons were recorded from the gracile nucleus in the rats with CCI. Mechanical evoked responses were significantly depressed following application of AMPA receptor antagonist, CNQX, with noxious and non-noxious responses being similarly affected. AP-5, an NMDA receptor antagonist, induced depression of the pressure-evoked response only after application of the 1-microM concentration of this drug. The size of the receptive fields was significantly decreased after CNQX, but not MK-801 or AP-5, application. Afterdischarge was significantly depressed following the application of CNQX (1000 microM). The expression of ionotropic glutamate receptor subunit mRNAs in the gracile nucleus was studied using the in situ hybridization technique. The signals for NMDA subunits, NR2A, -2B and -2C, in the gracile nucleus neurons were not prominent, suggesting a low level expression of functional NMDA receptor complex. AMPA receptor subunits GluR1, -R2, -R3 and -R4 mRNAs were expressed in a large number of gracile nucleus neurons. These data are consistent with the pharmacological results that AMPA receptor antagonists depressed nociceptive neuronal activity, but NMDA receptor antagonists showed limited effects. These results suggest that the ionotropic glutamate receptors, i.e. the AMPA and NMDA receptors, are differentially involved in modulation of the wide dynamic range neuronal activity in the gracile nucleus following peripheral nerve injury.
Pain 02/2002; 95(1-2):153-63. · 5.78 Impact Factor
