ABSTRACT
OBJECTIVE Trigeminal pain is mostly uni-lateral orofacial,but pain sensitization often spreads to contralateral orofacial or distal body regions.Widespread trigeminal pain has more severe intensity,longer dura-tion,and wider distribution,accompanied by more serious comorbid emotional syndrome.Unfortunately,the first-line analgesics for neuropathic pain has limited effect on widespread pain along with unavoidable side effects.In-depth understanding of the pathogenesis of wide-spread trigeminal pain is urgently needed.METHODS Trigeminal pain was induced by partial transection of the infraorbital nerve(p-IONX)and evaluated by measur-ing nociceptive thresholds to mechanical or heat stimula-tion.Neuronal activity was evaluated by single-unit and patch clamp recordings.HMGB1 expression was mea-sured by immunohistochemistry.Antagonism of HMGB1 was achieved by injecting anti-HMGB1 monoclonal anti-body(mAb)intracerebrally or intraperitoneally.RESULTS P-IONX model induced not only orofacial algesia but also somatic algesia in hind paw.Spontaneous firing frequency of glutamatergic neurons in the ventral posteromedial tha-lamic nucleus(VPMGlu)as well as the amplitude and fre-quency of sEPSCs significantly increased after p-IONX.Moreover,calcium signal recording showed that VPMGlu became to be activated by the noxious mechanical stimu-lation given on the hind paw,suggesting that VPMGlu recruited somatic afferents after p-IONX.We further explored the upstream brain regions of VPMGlu by virus retrograde tracing.We found the afferents from the grac-ile nucleus/cuneate nucleus(Gr/Cu),which are involved in the conduction of somatic sensation,markedly increased.And chemogenetical inhibiting Gr/Cu-VPM circuit alleviated the widespread neuropathic pain.In addition,the expression of HMGB1 in the VPM was sig-nificantly increased after p-IONX.Local administration of anti-HMGB1 mAb in the VPM relieved widespread neuro-pathic pain in mice receiving p-IONX.CONCLUSION These results demonstrate that the remodeling of affer-ent neurons in VPM underlie the spreading of wide-spread trigeminal neuropathic pain.Highly expressed HMGB1 in VPM plays an important role in these patho-logical changes after nerve injury and systemic adminis-tration of anti-HMGB1 mAb concurrently relieves wide-spread pain.
ABSTRACT
The present study investigated the role of spinal glutamate recycling in the development of orofacial inflammatory pain or trigeminal neuropathic pain. Experiments were carried out on male Sprague-Dawley rats weighing between 230 and 280 g. Under anesthesia, a polyethylene tube was implanted in the atlanto-occipital membrane for intracisternal administration. IL-1β-induced inflammation was employed as an orofacial acute inflammatory pain model. IL-1β (10 ng) was injected subcutaneously into one vibrissal pad. We used the trigeminal neuropathic pain animal model produced by chronic constriction injury of the infraorbital nerve. DL-threo-β -benzyloxyaspartate (TBOA) or methionine sulfoximine (MSO) was administered intracisternally to block the spinal glutamate transporter and the glutamine synthetase activity in astroglia. Intracisternal administration of TBOA produced mechanical allodynia in naïve rats, but it significantly attenuated mechanical allodynia in rats with interleukin (IL)-1 β-induced inflammatory pain or trigeminal neuropathic pain. In contrast, intracisternal injection of MSO produced anti-allodynic effects in rats treated with IL-1β or with infraorbital nerve injury. Intracisternal administration of MSO did not produce mechanical allodynia in naive rats. These results suggest that blockade of glutamate recycling induced pro-nociception in naïve rats, but it paradoxically resulted in anti-nociception in rats experiencing inflammatory or neuropathic pain. Moreover, blockade of glutamate reuptake could represent a new therapeutic target for the treatment of chronic pain conditions.
Subject(s)
Animals , Humans , Male , Rats , Amino Acid Transport System X-AG , Anesthesia , Astrocytes , Chronic Pain , Constriction , Glutamate-Ammonia Ligase , Glutamic Acid , Hyperalgesia , Inflammation , Interleukins , Membranes , Methionine Sulfoximine , Models, Animal , Neuralgia , Polyethylene , Rats, Sprague-Dawley , RecyclingABSTRACT
La gabapentina es un agente útil para el alivio de la neuralgia del trigémino y el dolor orofacial fantasma. Sin embargo, existe poca información sobre el efecto antinociceptivo de la gabapentina en los modelos de dolor orofacial. En este trabajo se investigó el efecto antinociceptivo de la gabapentina sobre el acicalado facial en la rata, provocado por la inyección de la formalina, un paradigma de dolor orofacial. La dosis de 10 mg/kg IP de la gabapentina produjo una drástica disminución del acicalado facial en la fase I y II indicando un claro efecto antinociceptivo. Sin embargo, en la dosis de 1 mg/kg IP, la gabapentina tuvo un efecto antinociceptivo sólo en la fase I. La D-serina (100 µg, ICV) no produjo efecto inyectada sola y no antagonizó el efecto antinociceptivo de la gabapentina. Por el contrario, la combinación de la gabapentina-1 mg/kg IP más D-serina redujo significativamente el acicalado facial en la fase II. Este resultado muestra una diferencia con estudios en que la gabapentina induce antinocicepción en la prueba de la formalina en la pata de la rata sólo en la fase II y la D-serina antagoniza a la gabapentina. Los resultados se discuten en relación al proceso de dolor en la pata posterior versus la estimulación dolorosa orofacial.
Gabapentin is a useful agent for the relief of trigeminal neuralgia and orofacial phantom pain. However, there is scarce information on the gabapentin analgesic effect in orofacial pain models. We tested the analgesic action of gabapentin on the formalin-induced face grooming in the rat, an orofacial pain paradigm. IP Gabapentin (10 mg/kg), induced a drastic reduction in face grooming during phase I and II, indicating a clear-cut antinociceptive effect. However, at 1 mg/kg, gabapentin had an analgesic effect only on phase I. D-serine (100 µg, ICV) was silent when given alone and did not antagonize the antinociceptive effect of gabapentin. On the contrary, gabapentin 1 mg/kg plus D-serine significantly reduced face grooming in phase II. These results show a difference between gabapentin induced orofacial analgesia and previous studies showing gabapentin-induced hind paw analgesia in the formalin test, only during phase II, as well as D-serine antagonism of gabapentin. The results are discussed in terms of different pain processing of hind paw, versus orofacial nociceptive stimulation.
Subject(s)
Animals , Rats , Analgesics/therapeutic use , Pain Measurement/methods , Facial Pain/therapy , Trigeminal Neuralgia/therapyABSTRACT
The authors report a cases of the epidermoid cyst which manifested neuralgia on the 2nd and 3rd brances of the trigeminal nerve. The tumor was located in the cerebelloponitine angle, Lt. The cyst content and tumor capsule surrounding the trigeminal nerve were removed. After surgery, the chief complaint disappeared and other complications were absent. In the patient, the computed tomography scan demonstrated a hypodense tumor not enhanced by contrast material. With magnetic resonance imaging, the tumor showed a intermediate signal intensity between the brain and CSF on the T1-seighted image and an increased signal intensity relative to brain CSF on T2-weighted image. In the patient with trigeminal pain, we have to evaluate the causes of the pain radiologically.