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Purpose: To elucidate the differences in ocular biometric parameters by generation and gender and to identify axial length (AL)-associated genetic variants in Japanese individuals, we analyzed Tohoku Medical Megabank Organization (ToMMo) Eye Study data. Design: We designed the ToMMo Eye Study, examined AL variations, and conducted genome-wide association studies (GWASs). Participants: In total, 33 483 participants aged > 18 years who were recruited into the community-based cohort (CommCohort) and the birth and three-generation cohort (BirThree Cohort) of the ToMMo Eye Study were examined. Methods: Each participant was screened with an interview, ophthalmic examinations, and a microarray analysis. The GWASs were performed in 22 379 participants in the CommCohort (discovery stage) and 11 104 participants in the BirThree Cohort (replication stage). We evaluated the associations of single nucleotide polymorphisms (SNPs) with AL using a genome-wide significance threshold (5 × 10-8) in each stage of the study and in the subsequent meta-analysis. Main Outcome Measures: We identified the association of SNPs with AL and distributions of AL in right and left eyes and individuals of different sexes and ages. Results: In the discovery stage, the mean AL of the right eye (23.99 mm) was significantly greater than that of the left eye (23.95 mm). This difference was reproducible across sexes and ages. The GWASs revealed 703 and 215 AL-associated SNPs with genome-wide significance in the discovery and validation stages, respectively, and many of the SNPs in the discovery stage were replicated in the validation stage. Validated SNPs and their associated loci were meta-analyzed for statistical significance (P < 5 × 10-8). This study identified 1478 SNPs spread over 31 loci. Of the 31 loci, 5 are known AL loci, 15 are known refractive-error loci, 4 are known corneal-curvature loci, and 7 loci are newly identified loci that are not known to be associated with AL. Of note, some of them shared functional relationships with previously identified loci. Conclusions: Our large-scale GWASs exploiting ToMMo Eye Study data identified 31 loci linked to variations in AL, 7 of which are newly reported in this article. The results revealed genetic heterogeneity and similarity in SNPs related to ethnic variations in AL.
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Although family studies and genome-wide association studies have shown that genetic factors play a role in glaucoma, it has been difficult to identify the specific genetic variants involved. We tested 669 single nucleotide polymorphisms (SNPs) from the region of chromosome 2 that includes the GLC1B glaucoma locus for association with primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG) in the Japanese population. We performed a two-stage case-control study. The first cohort consisted of 123 POAG cases, 121 NTG cases and 120 controls: the second cohort consisted of 187 POAG cases, 286 NTG cases, and 271 controls. Out of six SNPs showing significant association with POAG in the first round screening, seven SNPs were tested in the second round. Rs678350 in the HK2 gene coding sequence showed significant allelic (p=0.0027 in Stage Two, 2.7XE-4 in meta-analysis) association with POAG, and significant allelic (p=4.7XE-4 in Stage Two, 1.0XE-5 in meta-analysis) association with NTG. Although alleles in the TMEM182 gene did not show significant association with glaucoma in the second round, subjects with the A/A allele in TMEM182 rs869833 showed worse visual field mean deviation (p=0.01). Even though rs2033008 in the NCK2 gene coding sequence did not show significant association in the first round, it had previously shown association with NTG so it was tested for association with NTG in round 2 (p=0.0053 in Stage Two). Immunohistochemistry showed that both HK2 and NCK2 are expressed in the retinal ganglion cell layer. Once multi-testing was taken into account, only HK2 showed significant association with POAG and NTG in Stage Two. Our data also support previous reports of NCK2 association with NTG, and raise questions about what role TMEM182 might play in phenotypic variability. Our data suggest that HK2 may play an important role in NTG in the Japanese population.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Predisposição Genética para Doença/genética , Hexoquinase/genética , Glaucoma de Baixa Tensão/genética , Proteínas Oncogênicas/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Frequência do Gene , Genótipo , Humanos , Imuno-Histoquímica , Japão , Glaucoma de Baixa Tensão/etnologia , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: The aim of this study was to compare the anti-inflammatory efficacy of preservative-free and preserved 0.1% diclofenac eye drops for the management of postoperative inflammation after cataract surgery in patients with nonproliferative diabetic retinopathy and in normal controls. METHODS: Forty-two diabetic patients and 50 normal control patients who underwent small-incision phacoemulsification cataract surgery bilaterally received topical preservative-free diclofenac in 1 eye and preserved diclofenac in the other eye. The corrected distance visual acuity (CDVA) as determined by a logarithm of the minimum angle of resolution (logMAR) chart, intraocular pressure (IOP), foveal thickness (FT) using optical coherence tomography (OCT), and the anterior chamber flare (ACF) score measured with a laser flare cell meter were monitored for 12 weeks after surgery. RESULTS: In the eyes with diabetic retinopathy, there were no significant differences in CDVA, IOP, FT, and ACF score between the right and left eyes at the initial exam. After cataract surgery, changes in CDVA, IOP, and FT were not influenced by the preservative in the diclofenac eye drops. In contrast, the ACF score in the eyes treated with preserved diclofenac showed slower recovery from postoperative inflammation than the eyes treated with preservative-free diclofenac. In the normal control eyes, similar but milder changes were observed in each of the clinical parameters. CONCLUSIONS: Because preservative suppressed the anti-inflammatory efficacy of topical diclofenac after cataract surgery, preservative-free diclofenac may have an improved safety profile during postoperative treatment, especially in patients with diabetic retinopathy.
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Anti-Inflamatórios/administração & dosagem , Catarata/terapia , Retinopatia Diabética/cirurgia , Diclofenaco/administração & dosagem , Soluções Oftálmicas/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/efeitos adversos , Estudos de Casos e Controles , Extração de Catarata/métodos , Humanos , Inflamação/prevenção & controle , Pressão Intraocular/efeitos dos fármacos , Pessoa de Meia-Idade , Soluções Oftálmicas/efeitos adversos , Facoemulsificação/métodos , Conservantes Farmacêuticos/administração & dosagem , Conservantes Farmacêuticos/efeitos adversos , Estudos Prospectivos , Tomografia de Coerência Óptica/métodos , Acuidade Visual/efeitos dos fármacosRESUMO
PURPOSE: To determine whether polymorphisms in the ARMS2 (LOC387715) gene and the lysyl oxidase-like 1 (LOXL1) gene are associated with age-related macular degeneration (AMD) in Japanese patients. DESIGN: Clinically relevant laboratory investigation. METHODS: Forty-one unrelated Japanese subjects with dry AMD, 50 subjects with exudative (wet) AMD, and 60 subjects with polypoidal choroidal vasculopathy (PCV) were studied. The single nucleotide polymorphisms (SNPs), p.Ala69Ser of the ARMS2 gene and p.Arg141Leu of the LOXL1 gene, were amplified by polymerase chain reaction, directly sequenced, and genotyped. RESULTS: For the ARMS2 gene, the genotype frequency of the p.Ala69Ser single nucleotide polymorphism in eyes with dry AMD was not significantly different from that in the controls (P = .04), but the frequency was significantly higher in the exudative AMD group (P = 3.1 × 10(-8)) and PCV group (P = 6.9 × 10(-3)). For the LOXL1 gene, the genotype frequency of the p.Arg141Leu single nucleotide polymorphism was not statistically higher in the dry AMD and PCV groups than in the control group (dry AMD, P = .05; PCV, P = .16), but was statistically higher in the exudative AMD group (P = 6.8 × 10(-3)). Regression analyses showed significant associations between the ARMS2 gene and LOXL1 gene in patients with exudative AMD. CONCLUSIONS: The p.Ala69Ser polymorphism of the ARMS2 gene is strongly associated with exudative AMD and PCV and is associated marginally with dry AMD. The polymorphisms in the LOXL1 gene did not predispose the individual to dry AMD and PCV. These findings suggest that there is a significant association between the ARMS2 gene and LOXL1 gene in exudative AMD.
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Aminoácido Oxirredutases/genética , Povo Asiático/genética , Degeneração Macular/genética , Polimorfismo de Nucleotídeo Único , Proteínas/genética , Idoso , Doenças da Coroide/genética , Feminino , Frequência do Gene , Genótipo , Atrofia Geográfica/genética , Humanos , Masculino , Doenças Vasculares Periféricas/genética , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Degeneração Macular Exsudativa/genéticaRESUMO
PURPOSE: To evaluate the effectiveness of pre-seasonal treatment with topical olopatadine on the reduction of clinical symptoms of seasonal allergic conjunctivitis (SAC). DESIGN: Prospective interventional case series. METHODS: Eleven patients with SAC received topical olopatadine in one eye at least two weeks before the onset of allergy symptoms, and the other eye served as the control. After the onset of allergic conjunctivitis, both eyes were treated with topical olopatadine. Visual analogue scale (VAS), which evaluated the subjective symptoms of ocular allergy, and the tear levels of histamine and substance P were measured up to six weeks. RESULTS: At the onset of allergy symptoms, the VAS score in the pretreatment eyes was statistically significantly lower than that in the control eyes. The VAS score in the control eyes decreased with time but did not decrease to the level seen in the pretreatment eyes until four weeks later. The tear level of substance P at the onset of allergy symptoms was significantly suppressed in the pretreatment eyes, while the level of histamine was not suppressed. Alteration of the VAS scores in the pretreatment eyes significantly correlated with the level of substance P, but not of histamine. CONCLUSIONS: To suppress clinical symptoms in patients with SAC, pre-seasonal treatment with topical olopatadine is effective. The effectiveness of treatment correlates with the tear level of substance P.
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Conjuntivite Alérgica/tratamento farmacológico , Dibenzoxepinas/uso terapêutico , Antagonistas não Sedativos dos Receptores H1 da Histamina/uso terapêutico , Pré-Medicação , Administração Tópica , Adulto , Conjuntivite Alérgica/metabolismo , Conjuntivite Alérgica/fisiopatologia , Dibenzoxepinas/administração & dosagem , Feminino , Histamina/metabolismo , Antagonistas não Sedativos dos Receptores H1 da Histamina/administração & dosagem , Humanos , Imunoglobulina E/sangue , Masculino , Cloridrato de Olopatadina , Soluções Oftálmicas/administração & dosagem , Soluções Oftálmicas/uso terapêutico , Medição da Dor , Pólen , Estudos Prospectivos , Estações do Ano , Substância P/metabolismo , Lágrimas/metabolismo , Resultado do TratamentoAssuntos
Estenose das Carótidas/epidemiologia , Oclusão da Artéria Retiniana/epidemiologia , Estenose das Carótidas/sangue , Estenose das Carótidas/diagnóstico , Diabetes Mellitus/epidemiologia , Feminino , Angiofluoresceinografia , Hemoglobinas Glicadas/metabolismo , Humanos , Hiperlipidemias/epidemiologia , Incidência , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Oftalmoscopia , Oclusão da Artéria Retiniana/sangue , Oclusão da Artéria Retiniana/diagnóstico , Ultrassonografia Doppler em CoresRESUMO
PURPOSE: Mutations of the CYP1B1 gene cause primary congenital glaucoma (PCG), Peters anomaly, and juvenile open-angle glaucoma (JOAG). The aim of this study was to determine the spectrum and role of the CYP1B1 gene in Japanese patients with PCG or JOAG. METHODS: Genomic DNA was extracted from the leukocytes of 18 unrelated patients with PCG and 21 unrelated patients with JOAG. All of the patients developed high intraocular pressure (IOP) before the age of 35 years. One hundred unrelated healthy adults with normal IOP were examined in the same way. The three exons of the CYP1B1 gene were amplified by polymerase chain reaction and directly sequenced. RESULTS: Mutational screening and sequence analyses of the CYP1B1 gene revealed four mutations in four patients with PCG: p.Asp192Val, c.4776insAT, p.Val364Met, and p.Asp430Glu. The first three mutations have been reported in other Japanese PCG patients, but Asp430Glu is a new mutation. No mutations were found in the CYP1B1 gene of the JOAG patients. CONCLUSIONS: PCG in approximately 20% of Japanese patients may be associated with CYP1B1 mutations, but JOAG is not. The three mutations p.Asp192Val, c.4776insAT, and p.Val364Met appear to be common in the Japanese population and might be useful in genetic screening for PCG.
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Sistema Enzimático do Citocromo P-450/genética , Glaucoma de Ângulo Aberto/genética , Hidroftalmia/genética , Mutação , Adolescente , Adulto , Hidrocarboneto de Aril Hidroxilases , Povo Asiático/genética , Pré-Escolar , Citocromo P-450 CYP1B1 , Análise Mutacional de DNA , Éxons/genética , Feminino , Glaucoma de Ângulo Aberto/congênito , Humanos , Pressão Intraocular , Japão/epidemiologia , Masculino , Linhagem , Análise de Sequência de DNA , Adulto JovemRESUMO
BACKGROUND: To report the results of immunohistochemical analyses of a retinal angioma obtained from a patient with von Hippel-Lindau (VHL) disease. CASE: A 13-year-old girl with VHL disease presented with bilateral retinal angiomas and decreased vision in the right eye. Although transpupillary thermotherapy was performed to treat the angiomas, the tractional and exudative retinal detachment progressed OD, requiring vitreous surgery. Intraoperatively, a large retinal angioma was excised together with the surrounding retina to aid in reattaching the retina. The excised tissue was prepared for standard histopathology and immunohistochemistry. OBSERVATIONS: Histological examination showed that the excised tissue was made up of highly vascularized cells, and the retina was gliotic. The stromal cells had intracytoplasmic vacuoles and were located between the numerous vessels. These findings are identical to those of a hemangioblastoma. The stromal cells stained positively for vascular endothelial growth factor and neuron specific enolase, and weakly for glial fibrillary acidic protein. Some of the stromal cells stained positively for inhibin alpha. Isolated erythropoietin-positive cells, indicative of developmentally arrested angioblasts, were observed among the endothelial cells. CONCLUSIONS: The results indicate that stromal cells in retinal angiomas are neuroectodermal in origin with immunohistochemical features, for example, inhibin alpha, similar to cerebellar hemangioblastomas and renal cell carcinomas associated with VHL disease.
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Hemangioma/metabolismo , Inibinas/metabolismo , Neoplasias da Retina/metabolismo , Doença de von Hippel-Lindau/metabolismo , Adolescente , Eritropoetina/metabolismo , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Hemangioma/patologia , Hemangioma/cirurgia , Humanos , Técnicas Imunoenzimáticas , Fosfopiruvato Hidratase/metabolismo , Neoplasias da Retina/patologia , Neoplasias da Retina/cirurgia , Células Estromais/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Doença de von Hippel-Lindau/patologia , Doença de von Hippel-Lindau/cirurgiaRESUMO
PURPOSE: To investigate the lysyl oxidase-like 1 (LOXL1) gene for single nucleotide polymorphism (SNP) variations in Japanese patients with exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) and to examine the phenotypes of the patients with these variations. METHODS: Fifty-six unrelated Japanese patients with XFS, including 36 patients with XFG, were studied. Genomic DNA was extracted from the leukocytes of peripheral blood, and three SNPs (rs1048661; p.Arg141Leu, rs3825942; p.Gly153Asp, and rs2165241) were identified. These SNPs were amplified by polymerase chain reaction (PCR), directly sequenced, and genotyped. RESULTS: Two nonsynonymous variants in exon 1 of LOXL1,rs1048661 and rs3825942, were found to be strongly associated with XFS including XFG. The frequency of the T allele (0.964) in rs1048661 in eyes with XFS was much higher in controls (0.507) with a p value of 7.7x10(-18). The odds ratio for the T allele in rs1048661 was 26.0 (95% confidence interval, 18.3-37.1). In the haplotype analysis, T-G was overrepresented in XFS subjects (p=7.7x10(-18)), showing a highly significant difference in frequency between primary open-angle glaucoma (POAG) and the control group (p=0.07), but the G-G and G-A haplotypes were less represented in XFS subjects (p=1.1x10(-11) and p=1.0x10(-4), respectively). However, an earlier study reported the strongest associated SNP with XFS and XFG, rs2165241, showed no association. CONCLUSIONS: SNPs of LOXL1 (rs1048661; Arg141Leu and rs3825942; Gly153Asp) are highly associated with XFS in the Japanese population. However, unidentified genetic or environmental factors independent of LOXL1 will most likely influence the phenotypic expression of the syndrome.
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Aminoácido Oxirredutases/genética , Povo Asiático/genética , Síndrome de Exfoliação/genética , Olho/patologia , Glaucoma/complicações , Glaucoma/genética , Polimorfismo de Nucleotídeo Único/genética , Idoso , Estudos de Casos e Controles , Síndrome de Exfoliação/complicações , Feminino , Frequência do Gene , Haplótipos , Humanos , Japão , Masculino , FenótipoRESUMO
PURPOSE: To examine the myocilin (MYOC) gene for mutations in Japanese patients with primary open-angle glaucoma (POAG) and to determine the phenotypes of the patients with the mutations. METHODS: One-hundred thirty-eight unrelated Japanese patients with POAG were studied. Genomic DNA was extracted from leukocytes of peripheral blood, and the three coding exons including the intron-exon boundaries were amplified by polymerase chain reaction (PCR) and directly sequenced bi-directionally. RESULTS: Two sequence variants were identified, one novel non-synonymous amino acid change (p.Gln297His) and one reported synonymous amino acid change (p.Ala363Thr). These mutations were not detected in the 118 ethnically-matched controls. p.Gln297His was found in a 70-year-old man, who developed POAG at a late age, and his intraocular pressure was high. p.Ala363Thr was found in two cases, and both patients developed POAG at an early age and had high intraocular pressures that responded poorly to medical treatment. CONCLUSIONS: Two non-synonymous variants, p.Gln297His and p.Ala363Thr, indicate that they are involved in the pathogenesis of POAG. p.Ala363Thr has been found in another Japanese population and would be useful in genetic testing.
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Povo Asiático/genética , Proteínas do Citoesqueleto/genética , Proteínas do Olho/genética , Glaucoma de Ângulo Aberto/genética , Glicoproteínas/genética , Mutação/genética , Idoso , Sequência de Bases , Análise Mutacional de DNA , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , LinhagemRESUMO
PURPOSE: To determine whether mutations in the WD repeat domain 36 gene (WDR36) are associated with primary open-angle glaucoma (POAG) in Japanese. Subjects with high tension glaucoma (HTG) and normal tension glaucoma (NTG) were analyzed separately. METHODS: One hundred and thirty-six unrelated Japanese patients with HTG and 103 unrelated patients with NTG were studied. Genomic DNA was extracted from peripheral blood leukocytes, and all 23 exons were amplified by polymerase chain reaction (PCR) and directly sequenced bidirectionally. RESULTS: Twenty sequence alterations were identified: 10 have already been reported (p.I264V, c.1494+90C>T, c.1494+143A>G, c.1609+89G>A, c.1775+89C>A, c.1965-30A>G, p.V714V, c.2170+217C>T, p.V727V, and c.2518+60G>C) and 10 were novel (p.D179D, p.Q270Q, p.M283R, c.898+63C>G, c.1074+20C>T, p.G459G, c.1884+26C>G, p.S664L, p.S664S, and p.P744P). One nonsynonymous amino acid change in exon 17, p.S664L, was identified in a patient with HTG. The frequency of the p.I264V variant was significantly higher in the HTG group than in the control group (p=0.01), but the frequency in the NTG group was not significantly different from the control group (p=0.12). The frequency of the c.1965-30A>G variant was also significantly higher in the HTG group than in the control group (p=0.03), but the frequency in the NTG group was not significantly different from the control group (p=0.06). CONCLUSIONS: One nonsynonymous variant, p.S664L, and the association of the allelic variants (p.I264V and c.1965-30A>G) in WDR36 and their prevalence in unrelated Japanese patients with HTG suggest that they are probably involved in the pathogenesis of HTG.
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Povo Asiático/genética , DNA/genética , Proteínas do Olho/genética , Variação Genética , Glaucoma de Ângulo Aberto/genética , Idoso , Sequência Conservada , Evolução Molecular , Feminino , Frequência do Gene , Genótipo , Glaucoma de Ângulo Aberto/fisiopatologia , Haplótipos , Heterozigoto , Homozigoto , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Campos VisuaisRESUMO
PURPOSE: To determine whether polymorphisms in the Complement Factor H (CFH) gene and the Hemicentin-1 gene at the ARMD1 locus are associated with dry age-related macular degeneration (AMD) in Japanese patients. DESIGN: Clinically relevant laboratory investigation. METHODS: Eighty unrelated Japanese patients with dry AMD and 196 Japanese control patients were studied. Two exons of the CFH gene and four exons of the Hemicentin-1 gene were amplified by polymerase chain reaction and sequenced directly. RESULTS: For the CFH gene, the frequency of the previously reported Tyr402His variant was not significantly higher in the AMD group than in the control group (P = .31). In the Hemicentin-1 gene, three sequence alterations (Asp5088Val, IVS99-13C/T, and His5245Gln) were detected, and the originally reported Gln5346Arg was not detected. CONCLUSION: The CFH gene and Hemicentin-1 genes do not appear to be involved in a statistically significant fraction of dry AMD cases in the Japanese population.
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Proteínas da Matriz Extracelular/genética , Degeneração Macular/genética , Polimorfismo de Nucleotídeo Único , Idoso , Povo Asiático/genética , Fator H do Complemento/genética , Éxons/genética , Feminino , Humanos , Imunoglobulinas , Japão/epidemiologia , Masculino , Reação em Cadeia da PolimeraseRESUMO
Diverging observations on secondary hyperalgesia to heat stimuli have been reported in the literature. No studies have investigated the importance of heat stimulus intensity and duration for the assessment of secondary heat hyperalgesia. The present study was designed to investigate systematically (1) if pain sensitivity to radiant heat stimuli (focused Xenon light) is altered in the area of secondary punctuate hyperalgesia induced by intradermal injection of capsaicin and (2) if heat stimulus duration and intensity had an influence on the ability to detect secondary heat hyperalgesia. Pain ratings to radiant heat stimuli from a focused xenon lamp were assessed within the area of secondary punctuate hyperalgesia in fifteen volunteers before and after intradermal injection of capsaicin. The stimulus conditions were systematically varied between three intensity levels (0.8, 1.0 and 1.2 x heat pain threshold (PT)) and four duration steps (200, 350, 500 and 750 ms). The present study shows that long duration (350-750 ms) and low intensity (0.8 and 1.0 x PT) radiant heat stimuli were adequate to detect secondary heat hyperalgesia.
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Temperatura Alta , Hiperalgesia/fisiopatologia , Adulto , Capsaicina , Humanos , Hiperalgesia/induzido quimicamente , Injeções Intradérmicas , Masculino , Dor/fisiopatologia , Medição da Dor , Limiar da Dor/efeitos dos fármacos , Fatores de TempoRESUMO
The relationship between induction of central sensitization and facilitation of temporal summation to repetitive stimulation is still unclear. The aim of this study was to investigate temporal summation before and after the induction of secondary hyperalgesia by two different experimental methods: capsaicin injection and controlled heat injury. The effect of each injury model was assessed on a separate day with an interval of at least 5 days. Twelve healthy volunteers participated. Each experiment was performed using electrical, radiant heat, mechanical impact, and punctuate stimuli consecutively. The pain threshold (PT) to a single stimulus and the summation threshold to five repetitive stimuli for electrical (2 Hz) and radiant heat (0.83 Hz) were assessed within the secondary hyperalgesic area. The degree of temporal summation for stimulus intensities of 0.8, 1.0, and 1.2 times the baseline pain thresholds were evaluated by the increase in visual analogue scale (VAS) scores from the first to the fifth stimulus of the train. Further, the degrees of temporal summation were assessed for mechanical impact and punctuate stimuli within the primary and secondary hyperalgesic areas. The contra-lateral forearm served as control (no injury). The pain threshold and the summation threshold to electrical and heat stimuli decreased significantly within the secondary hyperalgesic area after the injury induced by both heat injury or capsaicin injection. However, there was no temporal summation for heat and electrical stimuli in either model. In contrast, for the mechanical impact and punctuate mechanical stimuli the degree of temporal summation was significantly facilitated in the secondary hyperalgesic areas compared with the baseline and the control arm in both models. In the primary hyperalgesic area, the degree of temporal summation was facilitated to mechanical impact and punctuate stimuli but only following the capsaicin injection. In conclusion, the temporal summation mechanism for mechanical stimuli was facilitated in the secondary hyperalgesic area.