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ABSTRACT: In our present study, we studied the role of demyelination of the trigeminal nerve root in the development of prolonged nociceptive behavior in the trigeminal territory.
Under anesthesia, the Sprague-Dawley rats were mounted onto a stereotaxic frame and 3 μL of lysophosphatidic acid (LPA, 1 nmol) was injected into the trigeminal nerve root to produce demyelination. This treatment decreased the air-puff thresholds, persisted until postoperative day 130, and then returned to the preoperative levels 160 days after LPA injection. The LPA-treated rats also showed a significant hyper-responsiveness to pin-prick stimulation. We further investigated the antinociceptive and neuroprotective effects of progesterone in rats undergoing demyelination of the trigeminal nerve root. Progesterone (8, 16 mg/kg/day) was administered subcutaneously, beginning on the operative day, for five consecutive days in the LPA-treated rats. Treatment with progesterone produced significant early anti-allodynic effects and delayed prolonged anti-allodynic effects. The expression of protein zero (P0) and peripheral myelin protein 22 (PMP22) were significantly down-regulated in the trigeminal nerve root on postoperative day 5 following LPA injection. This down-regulation of the P0 and PMP22 levels was blocked by progesterone treatment.
These results suggest that progesterone produces antinociceptive effects through neuroprotective action in animals with LPA-induced trigeminal neuropathic pain. Moreover, progesterone has potential utility as a novel therapy for trigeminal neuropathic pain relief at an appropriate managed dose and is therefore a possible future treatment strategy for improving the recovery from injury.
Molecular Pain 03/2012; 8:16. · 3.53 Impact Factor
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ABSTRACT: We investigated the differential regulation of p-p38 MAPK or p-NF-κB in male Sprague-Dawley rats with inferior alveolar nerve injury resulting from mal-positioned dental implants. For this purpose, we characterized the temporal expression of p-p38 MAPK or p-NF-κB in the medullary dorsal horn and examined changes in nociceptive behavior after a blockade of p-p38 MAPK or p-NF-κB pathways in rats with trigeminal neuropathic pain.
Under anesthesia, the left lower second molar was extracted and replaced with a mini dental implant to intentionally injure the inferior alveolar nerve. Western and immunofluorescence analysis revealed that p-p38 MAPK is upregulated in microglia following nerve injury and that this expression peaked on postoperative day (POD) 3 through 7. However, the activation of p-NF-κB in astrocyte peaked on POD 7 through 21. The intracisternal administration of SB203580 (1 or 10 μg), a p38 MAPK inhibitor, on POD 3 but not on POD 21 markedly inhibits mechanical allodynia and the p-p38 MAPK expression. However, the intracisternal administration of SN50 (0.2 or 2 ng), an NF-κB inhibitor, on POD 21 but not on POD 3 attenuates mechanical allodynia and p-NF-κB expression. Dexamethasone (25 mg/kg) decreases not only the activation of p38 MAPK but also that of NF-κB on POD 7.
These results suggest that early expression of p-p38 MAPK in the microglia and late induction of p-NF-κB in astrocyte play an important role in trigeminal neuropathic pain and that a blockade of p-p38 MAPK at an early stage and p-NF-κB at a late stage might be a potential therapeutic strategy for treatment of trigeminal neuropathic pain.
Molecular Pain 08/2011; 7:57. · 3.53 Impact Factor
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ABSTRACT: The present study is the first to investigate the participation of central cyclooxygenase (COX) pathways in modulating the antinociceptive effects of intracisternally administered cannabinoid on nociception induced by inflammation of the temporomandibular joint (TMJ) in freely moving rats. Following intra-articular injection of 5% formalin in the TMJ, nociceptive scratching behavior was recorded for nine successive 5-min intervals in Sprague-Dawley rats. Intracisternal injection of 30 microg of WIN 55,212-2, a synthetic non-subtype-selective CB1/2 agonist, administered 20 min prior to formalin injection significantly reduced the number of scratches and duration of scratching induced by formalin compared with the vehicle-treated group. Antinociceptive effect of WIN 55,212-2 was blocked by intracisternal injection of 10 microg of AM251, a CB1 receptor-selective antagonist, but not by AM630, a CB2 receptor-selective antagonist. A 10 microg dose of WIN 55,212-2 that was ineffective in producing antinociception became effective following intracisternal administration of NS-398, a selective COX-2 inhibitor; indomethacin, a non-selective COX 1/2 inhibitor; acetaminophen, a putative COX-3 inhibitor, but not following pretreatment with the selective COX-1 inhibitor, SC-560. The ED(50) value of WIN 55,212-2 in the NS-398-treated group was significantly lower than that in the vehicle-treated group. Importantly, administration of low doses of COX inhibitors alone did not attenuate nociception. These results indicate that inhibition of central COX pathways, presumably via COX-2 inhibition, reduces inflammatory pain by enhancing the cannabinoid-induced antinociceptive effect. Based on our observations, combined administration of cannabinoids with COX inhibitors may hold a therapeutic promise in the treatment of inflammatory TMJ pain.
Pain 12/2007; 132(1-2):23-32. · 5.78 Impact Factor
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ABSTRACT: The present study was performed to investigate the modulatory role of certain interleukin (IL)-1β in nociception with a nociceptive jaw opening reflex and an orofacial formalin test in freely moving rats. In an acute pain model, 10 pg, 100 pg and 1 ng IL-1β injected intracisternally did not change the digastric eletromyogram (dEMG). However, 10 ng IL-1β suppressed dEMG to 76±8 % of control values. In an inflammatory pain model, 10 pg IL-1β injected intracisternally did not change formalin-induced noxious behavioral responses. However, 100 pg IL-1β increased formalin-induced noxious behavioral responses. At higher dose of 10 ng IL-1β, it did not increase formalin-induced behavioral responses. Pretreatment with IL-1 receptor antagonist abolished hyperalgesic response of 100 pg IL-1β. These results suggest that the intracisternal injection of IL-1β modulate the transmission of nociceptive information in the orofacial area. The hypo/hyper-algesic responses of central cytokines seem to depend on the pain model or dose related manner and the hyperalgesic action seems to be mediated by IL-1 receptor.
Neuroscience Research Communications 10/2002; 31(3):145 - 154.
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ABSTRACT: The present study was performed to evaluate the characteristics of excitory amino acid receptors in the synaptic transmission of trigeminovascular neurons in trigeminal subnucleus caudalis. Extracellular single-unit recording of trigeminovascular neurons driven from dura or the superior sagittal sinus was made with a central barrel of seven-barrel micropipette. DL-2 amino-5 phosphonovaleric acid, N-methyl-D-aspartic acid (NMDA) receptor antagonist, produced a reversible inhibition of mechanical-evoked responses in 10 of 12 examined trigeminovascular neurons. The maximal inhibition was 59 ± 5 % of the control. However, CNQX did not affect trigeminovascular neuronal responses. Substance P also facilitated NMDA-evoked responses in 8 of 10 examined trigeminovascular neurons. The maximal facilitation was 153 ± 13 % of the control. These results imply that the NMDA receptor has a major role in the transmission of vascular headache (migraine) in trigeminovascular neurons and substance P also seems to be involved in maintenance migraine symptom.
Neuroscience Research Communications 01/2002; 29(3):163 - 171.
