Eun Jung Lim

Intracisternal administration of mitogen-activated protein kinase inhibitors reduced mechanical allodynia following chronic constriction injury of infraorbital nerve in rats.

The present study investigated the role of mitogen-activated protein kinase (MAPK) in orofacial neuropathic pain following chronic constriction injury of the infraorbital nerve (ION-CCI). Experiments were carried out on male Sprague-Dawley rats weighing between 200 and 230 g. The ION was separated from adhering tissue, and two ligatures (5-0 chromic gut) were tied loosely around it. We examined the air-puff thresholds (mechanical allodynia), scores of pinprick (mechanical hyperalgesia), and face grooming frequency for acetone application (hypersensitivity for cold stimulation) - 3, 3, 6, 9, 12, 15, 20, 25, 30, and 40 days after surgery. ION-CCI produced mechanical allodynia, hyperalgesia, and cold hypersensitivity. We investigated whether administration of MAPKs inhibitors blocks ION-CCI-induced mechanical allodynia. Intracisternal administration with PD98059 or SB203580, a MEK inhibitor or a p38 MAPK inhibitor, respectively, significantly inhibited ION-CCI-induced mechanical allodynia in the orofacial area. These results indicate that the ION-CCI produced behavioral alterations in the orofacial area and those central MAPKs pathways contribute to orofacial neuropathic pain. Our findings suggest that MAPKs inhibitors have a potential role in treatment for orofacial neuropathic pain.

Role of peripheral group I and II metabotropic glutamate receptors in IL-1β-induced mechanical allodynia in the orofacial area of conscious rats

&NA; The present study investigated the role of peripheral group I and II metabotropic glutamate receptors (mGluRs) in interleukin‐1β (IL‐1β)‐induced mechanical allodynia in the orofacial area. Experiments were carried out on Sprague–Dawley rats weighing between 230 and 280 g. After subcutaneous administration of 0.01, 0.1, 1, or 10 pg of IL‐1β, we examined withdrawal behavioral responses produced by 10 successive trials of a ramp of air‐puffs pressure applied ipsilaterally or contralaterally to the IL‐1β injection site. The thresholds of air puffs were measured 10, 30, 60, 120, or 180 min after 25 μl of IL‐1β was administered through an implanted tube. Subcutaneous injection of IL‐1β produced bilateral mechanical allodynia. While the IL‐1β‐induced mechanical allodynia was blocked by pretreatment with an IL‐1 receptor antagonist, the IL‐1β‐induced mirror‐image mechanical allodynia was not blocked by an IL‐1 receptor antagonist injected into the contralateral side. Subcutaneous administration of CPCCOEt or LY367385, an mGluR1 antagonist, or MPEP or SIB1893, an mGluR5 antagonist, 10 min prior to injection of IL‐1β abolished IL‐1β‐induced mechanical allodynia. Pretreatment with APDC or DCG4, a group II mGluR agonist, blocked the IL‐1β‐induced mechanical allodynia. The anti‐allodynic effect induced by APDC was inhibited by pretreatment with LY341495, a group II mGluR antagonist. These results suggest that peripheral group I and II mGluRs participate in IL‐1β‐induced mechanical allodynia in the orofacial area. Peripheral group I mGluR antagonists blocked the IL‐1β‐induced mechanical allodynia, while peripheral group II mGluR agonists produced anti‐allodynic effects on IL‐1β‐induced mechanical allodynia in the orofacial area of rats.

Compression of the trigeminal ganglion produces prolonged nociceptive behavior in rats

The present study is the first demonstration of prolonged nociceptive behavior in the trigeminal region following compression of the trigeminal ganglion in rats. Experiments were carried out on male Sprague–Dawley rats mounted onto a stereotaxic frame under pentobarbital sodium anesthesia. For compression of the trigeminal ganglion, a 4% agar solution (8μl) was injected into the trigeminal ganglion through a stainless steel injector (24 gauge), which extended 2mm beyond the end of a guide cannula (21 gauge). Following agar injection, the injector and guide cannula were removed. In the control group, rats were sham operated without agar injection. Air‐puff thresholds (mechanical allodynia), pin prick responses (mechanical hyperalgesia), and spontaneous scratching behavior were examined 3 days before surgery and at 3, 7, 10, 14, 17, 21, 24, 30, and 40 days after surgery. Data were analyzed using a repeated measures ANOVA followed by multiple group comparisons using the LSD post‐hoc test. Air‐puff thresholds significantly decreased after compression of the trigeminal ganglion. Mechanical allodynia was established within 3 days and lasted beyond postoperative day 24. Mechanical hyperalgesia was also evident 3 days after compression and persisted until the 40th postoperative day. Although mechanical allodynia and hyperalgesia appeared bilaterally, the ipsilateral side was significantly more sensitive. Intraperitoneal treatment with carbamazepine significantly blocked mechanical allodynia produced by compression of the trigeminal ganglion. These findings suggest that prolonged nociceptive behavior following compression of the trigeminal ganglion may mimic trigeminal neuralgia in this animal model.

Intracisternal administration of chemokines facilitated formalin-induced behavioral responses in the orofacial area of freely moving rats.

The present study investigated the effects of intracisternal administration of MCP-1, Rantes or IL-8 on pain transmission in the orofacial area. We also investigated mechanisms of hyperalgesic responses produced by intracisternal administration of IL-8. An orofacial formalin test was employed to assess the effects of chemokines on nociceptive processing. For each animal, the number of behavioral responses and the time spent grooming, rubbing and/or scratching the facial region proximal to the formalin injection site was recorded for nine successive 5-min intervals. Intracisternal administration of MCP-1, Rantes or IL-8 significantly increased formalin-induced scratching behavioral responses in the orofacial area. Intracisternal pretreatment with indomethacin, a non-selective cyclooxygenase inhibitor, did not block IL-8-induced hyperalgesia. Pretreatment with 100 microg propranolol, a non-selective beta-adrenergic receptor antagonist and 50 microg atenolol, a selective beta(1)-adrenergic receptor antagonist, inhibited the number of scratches and the duration of scratching produced by 1 ng of IL-8 injected intracisternally. These results indicate that intracisternal administration of chemokines produce a hyperalgesic response with an orofacial inflammatory pain model and that the IL-8-induced hyperalgesia is mediated by central beta(1)-adrenergic receptor.

Participation of peripheral group I and II metabotropic glutamate receptors in the development or maintenance of IL-1β-induced mechanical allodynia in the orofacial area of conscious rats

The present study investigated the role of peripheral groups I and II metabotropic glutamate receptors (mGluRs) in interleukin (IL)-1beta-induced mechanical allodynia in the orofacial area of rats. Subcutaneous injection of 10 pg of IL-1beta decreased air-puff thresholds ipsilateral or contralateral to the injection site. The decrease in air-puff thresholds appeared 10 min after the injection of IL-1beta and IL-1beta-induced mechanical allodynia persisted for over 3 h. Pre-treatment with 7-(hydroxyimino) cyclopropa[b] chromen-1a-carboxylate ethyl ester (CPCCOEt) or 2-methyl-6-(phenylethynyl)-pyridine hydrochloride (MPEP), a mGluR1 or mGluR5 antagonist, blocked IL-1beta-induced mechanical allodynia and mirror-image mechanical allodynia produced by a subcutaneous injection of 10 pg of IL-1beta. However, post-treatment with CPCCOEt or MPEP did not affect changes in behavioral responses, which were produced by the IL-1beta injection. Pre-treatment, as well as post-treatment with (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC), a group II mGluR agonist, blocked either IL-1beta-induced mechanical allodynia or mirror-image mechanical allodynia. The anti-allodynic effects of APDC were abolished by pre-treatment with (2S)-2-amino-2[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid (LY341495), a group II mGluR antagonist. These results indicate that peripheral group II mGluRs are involved in the development and maintenance of IL-1beta-induced mechanical allodynia, while peripheral group I mGluRs are involved in the development of IL-1beta-induced mechanical allodynia. Based on our observations, the peripheral application of group II mGluR agonists may be of therapeutic value in treating inflammatory pain.

Reversible Sensorineural Hearing Loss due to Pachymeningitis Associated with Elevated Serum MPO-ANCA

Hypertrophic pachymeningitis is a progressive disease resulting in a diffuse thickening of dura mater due to inflammation, tumor or autoimmune diseases, but most cases are idiopathic. It is seldom reported to be related to sensorineural hearing loss, but it can cause sensorineural hearing loss which can be potentially reversed through treatment. Here, we report the case of a 54-year-old woman who had progressive, bilateral, worse in the left, sensorineural hearing loss and visual disturbance with an accompanying headache over several months. Brain MRI showed diffusely thickened dura mater, highly enhanced after gadolinium administration, which was consistent with pachymeningitis. It was assumed to be related to autoimmune pathogenesis on the basis of elevated serum myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) titers. After empirical steroid and cyclophosphamide therapy, auditory impairment improved, especially in the high frequency region of the pure tone audiogram, and significant improvement in the word recognition test. Moreover, a follow-up MRI revealed much decreased enhancement of the dura mater, and the MPO-ANCA titer decreased to within the normal range. In the case of rapidly progressive sensorineural hearing loss or hearing impairment accompanying other cranial neuropathy, pachymeningitis should be taken into consideration, and brain MRI with gadolinium enhancement is the best method of detecting it. Also, to ensure proper treatment, a cautious evaluation including an ANCA work-up should be performed.

Long-term effect of noise exposure during military service in South Korea

Abstract Objective: Most Korean men spend at least two years in the military service usually in their early twenties. The aim of this study was to identify the long-term effect of exposure to military noise during military service by comparing two regressions of age-related hearing loss between groups with and without exposure to military noise. Design: Cross-sectional observational study. Study sample: Finally, 4079 subjects were included, among 10,286 data of men’s audiogram from January 2004 to April 2010. We excluded repeated testers and any subjects who had other known external causes or had an asymmetric audiogram. We grouped subjects with exposure to military noise (N = 3163) and those without as the control group (N = 916). Results: There was a significant effect of exposure to military noise at 4 and 8 kHz after controlling for the effect of age. The annual threshold deterioration rates were faster in the military noise exposed group than in the control group at 1, 2 and 4 kHz (p < 0.05). Conclusion: The long-term effect of exposure to military noise on age-related hearing loss showed an adding effect at 8 kHz and an accelerating effect in the frequency region from 1 to 4 kHz.