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1.
Exp Neurol ; 267: 42-52, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25736265

RESUMO

In order to determine if the functional changes in the GABAergic system in the trigeminal spinal subnucleus caudalis (Vc) are involved in the mechanisms underlying extraterritorial neuropathic pain in the orofacial region following inferior alveolar nerve transection (IANX), mechanical noxious behavior, phosphorylated extracellular signal-regulated kinase (pERK) immunohistochemistry and single neuronal activity were analyzed in vesicular GABA transporter (VGAT)-VenusA rats expressing fluorescent protein and the VGAT in Vc neurons. The number of VGAT-VenusA positive neurons was significantly reduced in IANX rats than naive and sham rats at 7days after nerve transection. The number of VGAT-VenusA positive pERK-immunoreactive (IR) cells was significantly increased in IANX rats at 21days after IAN transection compared with naive and sham rats. The background activity and mechanical-evoked responses of Vc nociceptive neurons were significantly depressed after intrathecal application of the GABA receptor agonist muscimol in sham rats but not in IANX rats. Furthermore, the expression of potassium-chloride co-transporter 2 (KCC2) in the Vc was significantly reduced in IANX rats compared with sham rats. The head-withdrawal threshold (HWT) to mechanical stimulation of the whisker pad skin was significantly decreased in IANX rats compared with sham rats on days 7 and 21 after IANX. The significant reduction of the HWT and significant increase in the number of VGAT-VenusA negative pERK-IR cells were observed in KCC2 blocker R-DIOA-injected rats compared with vehicle-injected rats on day 21 after sham treatment. These findings revealed that GABAergic Vc neurons might be reduced in their number at the early period after IANX and the functional changes might occur in GABAergic neurons from inhibitory to excitatory at the late period after IANX, suggesting that the neuroplastic changes occur in the GABAergic neuronal network in the Vc due to morphological and functional changes at different time periods following IANX and resulting in the extraterritorial neuropathic pain in the orofacial region following trigeminal nerve injury.


Assuntos
Hiperalgesia/etiologia , Bulbo/patologia , Neurônios/fisiologia , Limiar da Dor/fisiologia , Traumatismos do Nervo Trigêmeo/complicações , Ácido gama-Aminobutírico/metabolismo , Acetatos/farmacologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/genética , Animais , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Agonistas de Receptores de GABA-A/farmacologia , Proteína Glial Fibrilar Ácida/metabolismo , Indenos/farmacologia , Nervo Mandibular/patologia , Nervo Mandibular/cirurgia , Muscimol/farmacologia , Neurônios/efeitos dos fármacos , Estimulação Física , Ratos , Ratos Transgênicos , Tempo , Traumatismos do Nervo Trigêmeo/etiologia , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/genética , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/metabolismo
2.
Eur J Oral Sci ; 122(6): 391-6, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25371244

RESUMO

Orofacial cold hyperalgesia is known to cause severe persistent pain in the face following trigeminal nerve injury or inflammation, and transient receptor potential (TRP) vanilloid 1 (TRPV1) and TRP ankylin 1 (TRPA1) are thought to be involved in cold hyperalgesia. However, how these two receptors are involved in cold hyperalgesia is not fully understood. To clarify the mechanisms underlying facial cold hyperalgesia, nocifensive behaviors to cold stimulation, the expression of TRPV1 and TRPA1 in trigeminal ganglion (TG) neurons, and TG neuronal excitability to cold stimulation following facial capsaicin injection were examined in rats. The head-withdrawal reflex threshold (HWRT) to cold stimulation of the lateral facial skin was significantly decreased following facial capsaicin injection. This reduction of HWRT was significantly recovered following local injection of TRPV1 antagonist as well as TRPA1 antagonist. Approximately 30% of TG neurons innervating the lateral facial skin expressed both TRPV1 and TRPA1, and about 64% of TRPA1-positive neurons also expressed TRPV1. The TG neuronal excitability to noxious cold stimulation was significantly increased following facial capsaicin injection and this increase was recovered by pretreatment with TRPA1 antagonist. These findings suggest that TRPA1 sensitization via TRPV1 signaling in TG neurons is involved in cold hyperalgesia following facial skin capsaicin injection.


Assuntos
Capsaicina/efeitos adversos , Temperatura Baixa/efeitos adversos , Dor Facial/etiologia , Hiperalgesia/etiologia , Fármacos do Sistema Sensorial/efeitos adversos , Canais de Cátion TRPC/fisiologia , Acetanilidas/farmacologia , Anilidas/farmacologia , Animais , Comportamento Animal , Capsaicina/farmacologia , Cinamatos/farmacologia , Eletromiografia/instrumentação , Face , Temperatura Alta/efeitos adversos , Injeções Intradérmicas , Masculino , Condução Nervosa/efeitos dos fármacos , Condução Nervosa/fisiologia , Neurônios/química , Neurônios/efeitos dos fármacos , Estimulação Física , Purinas/farmacologia , Ratos , Ratos Sprague-Dawley , Reflexo/efeitos dos fármacos , Reflexo/fisiologia , Fármacos do Sistema Sensorial/farmacologia , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/fisiologia , Canal de Cátion TRPA1 , Canais de Cátion TRPC/análise , Canais de Cátion TRPC/antagonistas & inibidores , Canais de Cátion TRPV/análise , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Cátion TRPV/fisiologia , Gânglio Trigeminal/química , Gânglio Trigeminal/efeitos dos fármacos
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