RESUMEN
BACKGROUND: We investigated the role of the central NMDA receptor NR2 subunits in the modulation of nociceptive behavior and p-p38 MAPK expression in a rat model with compression of the trigeminal nerve root. To address this possibility, changes in air-puff thresholds and pin-prick scores were determined following an intracisternal administration of NR2 subunit antagonists. We also examined effects of NR2 subunit antagonists on the p-p38 MAPK expression. RESULTS: Experiments were carried out using male Sprague-Dawley rats weighing (200-230 g). Compression of the trigeminal nerve root was performed under pentobarbital sodium (40 mg/kg) anesthesia. Compression of the trigeminal nerve root produced distinct nociceptive behavior such as mechanical allodynia and hyperalgesia. Intracisternal administration of 10 or 20 µg of D-AP5 significantly increased the air-puff threshold and decreased the pin-prick scores in a dose-dependent manner. The intracisternal administration of PPPA (1, 10 µg), or PPDA (5, 10 µg) increased the air-puff threshold and decreased the pin-prick scores ipsilateral as well as contralateral to the compression of the trigeminal root. Compression of the trigeminal nerve root upregulated the expression of p-p38 MAPK in the ipsilateral medullary dorsal horn which was diminished by D-AP5, PPPA, PPDA, but not Ro25-6981. CONCLUSIONS: Our findings suggest that central NMDA receptor NR2 subunits play an important role in the central processing of trigeminal neuralgia-like nociception in rats with compression of the trigeminal nerve root. Our data further indicate that the targeted blockade of NR2 subunits is a potentially important new treatments strategy for trigeminal neuralgia-like nociception.
Asunto(s)
Conducta Animal , Nociceptores/metabolismo , Radiculopatía/enzimología , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Raíces Nerviosas Espinales/patología , Nervio Trigémino/patología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Conducta Animal/efectos de los fármacos , Compuestos de Diazonio/administración & dosificación , Compuestos de Diazonio/farmacología , Vías de Administración de Medicamentos , Masculino , Actividad Motora/efectos de los fármacos , Nociceptores/efectos de los fármacos , Nociceptores/patología , Fenoles/administración & dosificación , Fenoles/farmacología , Fosforilación/efectos de los fármacos , Piperidinas/administración & dosificación , Piperidinas/farmacología , Piridinas/administración & dosificación , Piridinas/farmacología , Radiculopatía/patología , Radiculopatía/fisiopatología , Ratas , Ratas Sprague-Dawley , Receptores de N-Metil-D-Aspartato/metabolismo , Raíces Nerviosas Espinales/efectos de los fármacos , Raíces Nerviosas Espinales/enzimología , Raíces Nerviosas Espinales/fisiopatología , Nervio Trigémino/efectos de los fármacos , Nervio Trigémino/enzimología , Nervio Trigémino/fisiopatología , Regulación hacia Arriba/efectos de los fármacosRESUMEN
The present study investigated the role of peripheral opioid receptors in mustard oil-induced nociceptive behavior and inflammation in the masseter muscles of lightly anesthetized rats. Experiments were carried out on male Sprague-Dawley rats weighing between 300 and 400 g. After initial anesthesia with sodium pentobarbital (40 mg/kg, i.p.), one femoral vein was cannulated and connected to an infusion pump for the intravenous infusion of sodium pentobarbital. The rate of infusion was adjusted to provide a constant level of anesthesia. Mustard oil (MO, 30 microl) was injected into the mid-region of the left masseter muscle via a 30-gauge needle. Intramuscularly-administered morphine significantly reduced shaking behavior but not MO-induced inflammation. Intramuscular pretreatment with naloxone, an opioid receptor antagonist, reversed antinociception produced by intramuscularly-administered morphine, while intracisternal administration of naloxone did not affect the antinociception of peripheral morphine. Pretreatment with d-Pen-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), a mu opioid receptor antagonist, but not naltrindole, a delta opioid receptor antagonist, nor norbinaltorphimine (nor-BNI), a kappa opioid receptor antagonist, reversed intramuscularly-administered morphine-induced antinociception. These results indicate that intramuscularly-administered morphine produces antinociception in craniofacial muscle nociception and that this intramuscularly-administered morphine-induced antinociception is mediated by a peripheral mu opioid receptor. Our observations further support the clinical approach of administering opioids in the periphery for the treatment of craniofacial muscle nociception.