TLR8 in the Trigeminal Ganglion Contributes to the Maintenance of Trigeminal Neuropathic Pain in Mice / 神经科学通报·英文版

Trigeminal neuropathic pain (TNP) is a significant health problem but the involved mechanism has not been completely elucidated. Toll-like receptors (TLRs) have recently been demonstrated to be expressed in the dorsal root ganglion and involved in chronic pain. Here, we show that TLR8 was persistently increased in the trigeminal ganglion (TG) neurons in model of TNP induced by partial infraorbital nerve ligation (pIONL). In addition, deletion or knockdown of Tlr8 in the TG attenuated pIONL-induced mechanical allodynia, reduced the activation of ERK and p38-MAPK, and decreased the expression of pro-inflammatory cytokines in the TG. Furthermore, intra-TG injection of the TLR8 agonist VTX-2337 induced pain hypersensitivity. VTX-2337 also increased the intracellular Ca

Botulinum toxin-A injections as therapy for chronic painful post-traumatic trigeminal neuropathy: case report / Injeções de toxina botulínica-A como terapia para dor neuropática trigeminal pós-traumática crônica: relato de caso

Painful post-traumatic trigeminal neuropathy (PTTN) involves spontaneous and evoked pain, of moderate to severe intensity, continuous and described as burning or shooting. The first line treatment is pharmacological. However, botulinum toxin - A (BoNT-A) can be used when medications cannot control pain. This article describes the use of BoNT-A in a case of PTTN refractory to conventional pharmacological treatment. A 44-year-old male patient presented with an 8-years history of pain in the lower left second molar region. Pain was burning, lasting for seconds, with multiple pain episodes per day. Diagnosis hypothesis was PTTN. After no improvement with conventional pharmacological treatment, injections of BoNT-A were elected. Somatosensory assessment showed a significant reduction in visual analog scale for touch, cold and pinprick sensitivity. Likewise, patient's impression of change in pain significantly improved after BoNT-A injections. Our results suggest that BoNT-A could be used as a treatment for PTTN refractory to conventional treatments. (AU)

A neuropatia trigeminal pós-traumática dolorosa (PTTN) envolve dor espontânea e evocada, de intensidade moderada a grave, contínua e descrita como queimante ou lascinante. O tratamento de primeira linha é farmacológico. No entanto, a toxina botulínica - A (BoNT-A) pode ser usada quando os medicamentos não conseguem controlar a dor. Este artigo descreve o uso da BoNT-A em um caso de PTTN refratário ao tratamento farmacológico convencional. Paciente de sexo masculino, 44 anos, com 8 anos de dor na região do segundo molar inferior esquerdo. A dor foi descrita como queimante, com duração de segundos e com vários episódios por dia. A hipótese de diagnóstico foi PTTN. Após nenhuma melhora com o tratamento farmacológico convencional, as injeções de BoNT-A foram eleitas. A avaliação somatossensorial mostrou uma redução significativa na escala visual analógica para sensibilidade ao toque, frio e picada após BoNT-A. Da mesma forma, a impressão de mudança do paciente na dor melhorou significativamente após as injeções de BoNT-A. Nossos resultados sugerem que o BoNT-A poderia ser usada como tratamento para PTTN refratário a tratamentos convencionais. (AU)

Preemptive application of QX-314 attenuates trigeminal neuropathic mechanical allodynia in rats

The aim of the present study was to examine the effects of preemptive analgesia on the development of trigeminal neuropathic pain. For this purpose, mechanical allodynia was evaluated in male Sprague-Dawley rats using chronic constriction injury of the infraorbital nerve (CCI-ION) and perineural application of 2% QX-314 to the infraorbital nerve. CCI-ION produced severe mechanical allodynia, which was maintained until postoperative day (POD) 30. An immediate single application of 2% QX-314 to the infraorbital nerve following CCI-ION significantly reduced neuropathic mechanical allodynia. Immediate double application of QX-314 produced a greater attenuation of mechanical allodynia than a single application of QX-314. Immediate double application of 2% QX-314 reduced the CCI-ION-induced upregulation of GFAP and p-p38 expression in the trigeminal ganglion. The upregulated p-p38 expression was co-localized with NeuN, a neuronal cell marker. We also investigated the role of voltage-gated sodium channels (Navs) in the antinociception produced by preemptive application of QX-314 through analysis of the changes in Nav expression in the trigeminal ganglion following CCI-ION. Preemptive application of QX-314 significantly reduced the upregulation of Nav1.3, 1.7, and 1.9 produced by CCI-ION. These results suggest that long-lasting blockade of the transmission of pain signaling inhibits the development of neuropathic pain through the regulation of Nav isoform expression in the trigeminal ganglion. Importantly, these results provide a potential preemptive therapeutic strategy for the treatment of neuropathic pain after nerve injury.