Spinal Gap Junction Channels in Neuropathic Pain

Damage to peripheral nerves or the spinal cord is often accompanied by neuropathic pain, which is a complex, chronic pain state. Increasing evidence indicates that alterations in the expression and activity of gap junction channels in the spinal cord are involved in the development of neuropathic pain. Thus, this review briefly summarizes evidence that regulation of the expression, coupling, and activity of spinal gap junction channels modulates pain signals in neuropathic pain states induced by peripheral nerve or spinal cord injury. We particularly focus on connexin 43 and pannexin 1 because their regulation vastly attenuates symptoms of neuropathic pain. We hope that the study of gap junction channels eventually leads to the development of a suitable treatment tool for patients with neuropathic pain.

The relaxing effect of Poncirus fructus and its flavonoid content on porcine coronary artery / 한국실험동물학회지

Coronary artery disease is a common occurrence in human, and causes enormous social cost. Poncirus fructus (PF), the dried immature fruits of Poncirus trifoliata Rafinesquem, is used in the treatment of womb contraction and dyspepsia, as a prokinetic, and in improving blood circulation. This study was performed to investigate the effects of PF and some of its flavonoids components on the coronary from the pig. The arterial ring was suspended by a pair of stainless steel stirrups in an organ bath. The end of the upper stirrup was connected to an isometric force transducer. A dose-dependent induction of relaxation was observed by both water and 70% ethanol extracts of PF in the porcine coronary artery precontracted with U46619 (100 nM), a stable analogue of the potent vasoconstrictor thromboxane A2. The 70% ethanol extract showed more efficacy than the water extract. Pretreatment of the artery with L-NAME (100 microM), a nitric oxide synthase inhibitor, resulted in a significant reduction in the relaxation induced by PF extract. In addition, ODQ (10 microM), a soluble guanylate cyclase inhibitor, also significantly reduced the effects of PF extracts. Hesperidin, a flavonoid present in PF, induced very weak relaxation of the porcine coronary artery at a high concentration (100 microM), while its aglycone, hesperetin, demonstrated a dose-dependent relaxation. In conclusion, PF extracts induced relaxation in the porcine coronary artery, partially through the nitric oxide-cGMP pathway, and the aglycones of flavonoids might be also involved in the relaxation of the same artery.

Neuronal Hyperexcitability Mediates Below-Level Central Neuropathic Pain after Spinal Cord Injury in Rats / 한국실험동물학회지

Spinal cord injury often leads to central neuropathic pain syndromes, such as allodynic and hyperalgesic behaviors. Electrophysiologically, spinal dorsal horn neurons show enhanced activity to non-noxious and noxious stimuli as well as increased spontaneous activity following spinal cord injury, which often called hyperexcitability or central sensitization. Under hyperexcitable states, spinal neurons lose their ability of discrimination and encoding somatosensory information followed by abnormal somatosensory recognition to non-noxious and noxious stimuli. In the present review, we summarize a variety of pathophysiological mechanisms of neuronal hyperexcitability for treating or preventing central neuropathic pain syndrome following spinal cord injury.

Preventing Extracellular Diffusion of Trigeminal Nitric Oxide Enhances Formalin-induced Orofacial Pain

Nitric oxide (NO), a diffusible gas, is produced in the central nervous system, including the spinal cord dorsal horn and the trigeminal nucleus, the first central areas processing nociceptive information from periphery. In the spinal cord, it has been demonstrated that NO acts as pronociceptive or antinociceptive mediators, apparently in a concentration-dependent manner. However, the central role of NO in the trigeminal nucleus remains uncertain in support of processing the orofacial nociception. Thus, we here investigated the central role of NO in formalin (3%)-induced orofacial pain in rats by administering membrane-permeable or -impermeable inhibitors, relating to the NO signaling pathways, into intracisternal space. The intracisternal pretreatments with the NO synthase inhibitor L-NAME, the NO-sensitive guanylate cyclase inhibitor ODQ, and the protein kinase C inhibitor GF109203X, all of which are permeable to the cell membrane, significantly reduced the formalin-induced pain, whereas the membrane-impermeable NO scavenger PTIO significantly enhanced it, compared to vehicle controls. These data suggest that an overall effect of NO production in the trigeminal nucleus is pronociceptive, but NO extracellularly diffused out of its producing neurons would have an antinociceptive action.

Peripheral Nerve Injury Alters Excitatory and Inhibitory Synaptic Transmission in Rat Spinal Cord Substantia Gelatinosa

Following peripheral nerve injury, excessive nociceptive inputs result in diverse physiological alterations in the spinal cord substantia gelatinosa (SG), lamina II of the dorsal horn. Here, I report the alterations of excitatory or inhibitory transmission in the SG of a rat model for neuropathic pain ("spared nerve injury"). Results from whole-cell recordings of SG neurons show that the number of distinct primary afferent fibers, identified by graded intensity of stimulation, is increased at 2 weeks after spared nerve injury. In addition, short-term depression, recognized by paired-pulse ratio of excitatory postsynaptic currents, is significantly increased, indicating the increase of glutamate release probability at primary afferent terminals. The peripheral nerve injury also increases the amplitude, but not the frequency, of spontaneous inhibitory postsynaptic currents. These data support the hypothesis that peripheral nerve injury modifies spinal pain conduction and modulation systems to develop neuropathic pain.

Orbital Tissue Changes Induced by the Serum of Patients Suffering from Endocrine Exophthalmos

In endocrine exophthalmos. changes in the mucopolysaccharide in the orbital tissues are believed to play an important role, In order to investigate the changes induced by the exophthalmogenic factor in the serum of patients, the following experiment was undertaken. Male guinea pigs, 200-250g, were divided into four groups according to the treatment. Group I: Normal control, 5ml of normal saline was injected. Group II: 5ml of normal human serum was injected. Group III: 5ml of ptients' serum was injected. Group IV: TSH preparation (Ambinon, Organon), 5 International Unit was injected. All injections were repeated every day for 3 days, and 48 hours after the last injection, animals were bled to death and the tissues were removed. Water content of retrobulbar connective tissue, hexosamine and hydroxyproline content of Harder's gland and ventral lacrimal gland were determined. In animals treated with patient's serum, water content and hexosamine content increased significantly, whereas hydroxyproline showed no change. TSH preparation caused the same changes as the patient's serum. Aninlals injected with normal human serum showed no changes either in water content nor hexosamine and hydroxyproline content. The increased water content is considered to be followed by the accumulations of mucopolysaccharide, of which hexosamine is the main component. The possible relationship between exophthalmos-preducing factor and changes in orbital tissues were dicussed.

Medical Treatment of the Glaucoma

The goal of treatment in open-angle glaucoma is to prevent loss of visual function. If we prevent loss of function, our treatment is adequate. Our all treatment is designed to lower the pressure, either by increasing the facility of outflow or by suppressing formation of aqueous humor, or both. The drugs which used in medical treatment were listed. The steps in medical management were reviewed. Pilocarpine is our first and favorite drug(1-4%). A different approach, using epinephrine first may be indicated in certain young and myopic patients and in patients having axial lens opacities. Epinephrine 1 to 2% is added to the miotic treatment if tension remains not satisfactorily controlled. It is used 1 to 3 times a day. If 4% pilocarpine or its equivaleht plus epinephrine fail to bring about satisfactory lowering of tension, one of the stronger miotics can be substituted or added. The next step is the addition of carbonic anhydrase inhibitors orally, starting with acetazolamide 125mg 2 or 3 times a day, or its equivalent in some other drug. If more is necessary, and if the drug is tolerated. 1 gram a day, or its equivalent in some other drug is given in divided doses. Only when one is using 4% pilocarpine or its equivalent every 2 to 4 hours, epinephrine 1 to 3 times a day. with one of the stronger miotics added to the program or substituted for the weaker miotic. plus a carbonic anhydrase inhibitor to tolerance can one fed that maximum medical treatment is being employed. One can not speak of the failure of medical treatment and the necessity of operation unless the maximum tolerated medical treatment has been employed. and the tension is still not adequately controlled. Treatment depends on several factors, the most important of which are the height of the intraocular pressure; the age, health and life expectancy of the patient; the degree of disc and field damage; a family history of serious glaucoma; and the production of symptoms from use of antiglaucoma drugs. Medical treatment in angle-closure glaucoma was described. The medical therapy for angle-closure glaucoma is useful only as a prelude to surgery. Glycerol, Diamox, and pilocarpine may be used simultaneously to obtain prompt normalization of pressure. If the iris is not pulled away from the meshwork, peripheral anterior synechias may become permanent in a few hours. When pressure has become normalized, it is of utmost importance that the eye should be operated on promptly.

Immunosuppression of Corneal Graft Reaction by Azathioprine

1) The effectiveness of azathioprine (Imuran) in suppressing the immunogenic rejection of corneal grafts was studied by pathology. 2) The method of conjunctival implantation was used to produce neovascularization of the host cornea and the rejection of interlamellar allgraft and xenograft (rooster to rabbit) provided the experimental model against which the therapeutic efficacy of the drug was evaluated. There is almost same pathological finding between interlamellar homograft and heterograft. but the rejection phenomena of the heterograft group is slightly severer than homograft group. 3) On comparing the graft rejection between control and treated group in homograft and heterograft, the reaction in control group is severer than treated group. Microscopically, tbe cornea of treated group is almost transparent, but there are fibrosis of graft border, thickening of the host tissues and irregular arragement of corneal lamellae, by microscopically 4) On comparing between sensitized and non-sensitized group, no specific difference was observed by microspically.

Alkali Burns of the Cornea

1. Alkali burns of rabbit corneas were produced by 5.0 N NaOH swabbing the cornea and surrounding sclera. 2. Collagenolytic activity of alkali burned corneas, and the effectiveness of collagenase inhibitors (0.2 M cysteine sol. and 0.5% zinc sulfate sol.) in preventing the perforation of corneas were studied by pathology. 3. In control group, almost 85% of coreas were perforated, but in treated group, no corneal perforations were found. 4. In control group, epithelial and endothelial thickenings are evident and no neovascularization could be seen, in treated group neovascularization is evident and slight cellular reactions were visualized.

Attempts to Produce an Experimental Phlyetenulosis with BCG

There is general agreement that phlyctenular keratoconjunctivits is a manifestation of bacterial allergy, especially to products of the tubercle bacillus. Although the role of Mycobacterium tuberculosis to produce phlyctenules is well known, the exact mechanism of its production and the nature of involved immune reaction are not certain. Some previous reports informed that phlyctenular conjunctivitis occurred after BCG vaccination in the tuberculinnegative patient. This means that BCG vaccination changes immune balance and m!ly cause phlyctenule. The author attempted to produce phlyctenules in rabbits and guinea pigs in which BCG was used as the antigen to sensitize the animals systemically and PPD, living BCG and killed BCG were used as challenging agents. All but the animals which were injected with living and killed BCG subconjunctivally did not show any response. A primary tuberculosis lesion develo ped in the animals injected with living BCG and a pure abscess occured in the animals injected with killed BCG. It seems evident that the failure to produce phlyctenules in the BCG sensitized animals is ascribed to the relatively low order of sensitivity obtained as judged by the occurrence of primary tuberculosis.

Mycotic Uveitis-Diagnosis

Fungal infection of the uveal tract are rare and only sporadic cases have appeared in the literature; recently, however, these have become more numerous since antibiotic or steroid therapy undoubtedly encourages the proliferation of concomitant fungal diseases. Diagnosis of mycotic uveitis was summarized; the clinical diagnosis and laboratory diagnosis. A positive diagnosis of a fungus as the cause of an intraocular infammation is justified only when the actual fungus can be identified in the ocular lesions. The laboratory diagnosis of a fungus etiology for uveitis may therefore be discussed under two headings-the methods used for the direct demonstration of a fungus and the immunologic procedures employed to establish a presumptive diagnosis of a infection by an avirulent fungus. If material is not available for histologic examination, culture or animal inoculation, the positive demonstration of a fungus etiology is not possible, and the diagnosis must remain a presumptive one. Such a presumptive diagnosis is made on the combination of the ocular symptomatology, the presence of associated systemic changes believed indicative of a fungus infection, the exclusion of other probable etiologic factors, and the immunologic response of the patient to fungus antigens. Epidemiologic studies of presumed ocular histoplasmosis at Wilmer institude were summarized. Modern journals of mycotic infection of uvea were reviewed.

Ocular Hypertension

No abstract available.

The Effect of Experimental Silicone Encircling on Intraocular Pressure and Electroretinogram

The purpose of this study is to evaluate the course and prognosis of secondary glaucoma due to silicone encircling surgery for retinal detachment. The experiment was performed by observing the changes of elevated intraocular pressure and electroretinogram produced by silicone encircling in 20 rabbits. The rabbits were divided into 4 groups according to the elevattd level of intraocular pressure which was obtaintd by tightening of #240 silicone bands around the equator of the eyeball. The intraocular pressure was measured with a Schiotz tonometer and electroretinogram was recorded with a set of preamplifier, (freqwoncy reSponse 0.3-240 Hz, gain 80 decibel). Tektronix 5A18N dual trace amplifier, 5B12N dual time base, and 5103N oscilloscope. From the experiments, fo1lowing findings were obtained. 1. The effect on intraocular pressure. a) The elevated intraocular pressure returned to the preoperative level within 5-15 minutes in 35-45 mmHg group, 3-4 hours in 55-65 mmHg group, 4-6 hours in 75-85 mmHg group, and 7-8 hours in 95-105 mmHg group. b) In all the groaps, rapid fall of the intraocular pressure was observed within 10 minutes and relatively slow decrease was followed. From the second postoperative day, the intraocular pressure was maintained at a lower level than the preoperative intraocular pressure. 2. The effect on electroretinogram. a) In 35-45 mmHg group, supernormal wave was recorded during the 3 postoperative hours and then the wave returned to the preoperative amplitude. b) In 55-65 mmHg group, the electroretionogram reduced immediately after operation to 70% of the preoperative amplitude in 'a' wave and to 60% of the preoperative amplitude in 'b' wave' The reduced amplitude recovered to the preoperative level on the postoperative 1-2 days. c) In 75-85 mmHg group, both 'a' and 'b' wave were abolished immediately after the operation. The 'a' wave started to recover when the intraocular pressure decreased to 57.6-67.2 mmHg and 'b' wave started to recover when the intraocular pressure decreased to 49.9-57.6 mmHg. d) In 95-105 mmHg group, both 'a' and 'b' wave were abolished immediately after the oreration. The 'a' wave started to recover when the intraocular pressure decreased to 49.9-66.2 mmHg and 'b' wave started to recover when the intraocular pressure decreased to 37.2-40.2 mmHg. Consequently, it was found that the intraocular pressure over 75 mmHg caused irreversible damage to the function of retina, though the increased intraocular pressure due to silicone encircling returned to the preoperative level within 8 hours, and the visual cell layer of retina was more resistant to the increased intraocular pressure than the inner nuclear layer of retina.

Experimentally designed glaucoma implant surgery with mitomycin C in rabbit

An attempt was made to observe the possibility of controlling intraocular pressure (IOP) without hypotony and ocular motility disorder by installing an experimentally designed glaucoma implant through a small conjunctival incision with the aid of a stylet and maintaining the aqueous reservoir using mitomycin C (MMC). The implant was made of silicone tube, of which one end was occluded by glue and on the same end 4 check-valve-like slits were made. Thirty-five healthy white rabbits were used and subdivided into 4 groups. In groups I to III, implants having 2.0, 2.5, 3.0 mm slit lengths, respectively, were installed with MMC application in one eye of each of the 10 rabbits. In group IV, a 2 mm slit-length implant was installed without MMC in one eye of each of the 5 rabbits. Pneumatonometry and ultrasonography were performed to check the IOP and the formation of aqueous reservoir in the implanted eyes for 8 weeks. In group I through III, there was a statistically significant 4-5 mmHg pressure-lowering effect in the implanted eyes compared to the contralateral control eyes for 8 weeks. The aqueous reservoirs were observed throughout the follow-up period. In group IV, we could observe neither a pressure-lowering effect nor aqueous reservoir formation in the implanted eyes after 2 weeks postoperatively. Hypotony did not occur in implanted eyes in any of the groups. This study shows the possibility of IOP control by installing a specially designed glaucoma implant with application of MMC.

The Color Sense of Pseudophakic Eyes

We performed Farnsworth-Munsell 100-hue test in pseudophakic eyes and phakic eyes to detect the abnormal color perception suggested in pseudophakic eyes compared with phakic eyes. But there were no significant differences in total error scores and mean error scores at four individual boxes between two groups. The results suggest that there were no differences in color perception between pseudophakic and phakic eyes by Farnsworth-Munsell 100-hue test.

A Clinical Evaluations of Trabeculectomy

The authors analysed 30 eyes that "Trabeculectomy ab externo" was performed in S.N.U.H. Trabeculectomy was preferable operation in simple glaucoma and even in chronic closed angle glaucoma, but in congenital glaucoma, goniotomy was more preferable than trabeculectomy. In its mode of action, trabeculectomy was regarded as a sort of filtering precedure.

Experimental Iridocyclectomy

Management of the tumor of the iris and ciliary body is a difficult prablem. 244 cases of iridocyclectomy rather than enucleation had been reported from 1912 to 1970. But there seems to be no histopathological report. The author performed experimental iridocyclectomy in 20 albino rabbits, and observed clinically and pathologically one week interval for 6 weeks post-operathively. Surprisingly only a few cases of complications such as hyphema, vitreous hemorrhage and retinal detachment were observed. Post-operative wound healing was good. So the author concluded, "Iridocyclectomy itself isa delicate and difficult surgery, but skillful technique in a definitely indicated case using a operating microscope will get good result".

3 Cases of Mixed Tumor of Lacrimal gland

Here, we report 3 cases of mixed tumor of the lacrimal gland. The age of the patients were 43, 26 and 35 respectively. The two of these were male and one female. The most outstanding complaint was exopthalmos. A mass was palpated on the orbit and eye ball deviation in downward position was present in all cases. Pathologic findings were mixed tumor of the lacrimal gland with no evidence of malignancy. These tumors were well encapsulated and any evidence of involving bone and soft tissue was not found. Modified Kroenlein-Berke operation was performed and tumor mass was removed entirely with finger dissection in all cases. The vision was not improved but the cosmetic result was satisfactorr.

Postural Effect on the Intraocular Pressure: Clinical application of Perkins applanation tonometer, 1st report

In 44 normal, 15 controlled glaucomatous and 8 uncontrolled glaucomtous eyes, the influence of body positin on the intraocular pressure was studied using Perkins applanation tonometer. The pressure increment when changing from the seated to supine positin averaged 2.7 mm Hg in normal eyes. 2.1 mmHg in controlled glaucomatous eyes and 3.7 mmHg in the uncon trolled glaucomatous eyes. Pressure increment in each group was highly significant. The increased pressure was reversible when returning to the original seated position. It appears that the clinically important pressure to be considered in the diagnosis and management is the supine pressure in addition to the seated pressure.

Ocular Rigidity in Korean

The Korean 218 normal eyes, 74 myopic eyes and 42 glaucomatous eyes were examined. The intraocular pressure were measured by Goldmann applanation tonometer and Schiotz indentation tonometer using the 5.5 gm plunger load successively. The occular rigidity was estimated from Friedenwald 1955 nomogram. In normal eyes, the average coefficient of ocular rigidity was 0.0221 (standard deviation 0.0058, range 0.0032~0.0370). There was a statistically significant increase with age. It was higher in males than in females. But there was no statistically significant difference between sex. In myopic eyes. the average coefficient of ocular rigidity was 0.0189. There was an increase with refractive power but it was not statistically significant. In glaucomatous eyes. the average coefficient of ocular rigidity was 0.0181 in the medication-treated group and 0.0163 in the operated group. They were significantly lower than in normal eyes statistically. But there was no significant differance between medication-treated and operated groups.