RESUMEN
Recent observations suggest the involvement of adenosine in the peripheral antinociceptive effect of amitriptyline in nerve-injury-induced neuropathic pain. The aim of the present investigation was to evaluate, firstly, the peripheral and systemic effects of amitriptyline on tactile allodynia in the streptozotocin (STZ)-induced diabetic rat model of neuropathic pain and, secondly, whether caffeine coadministration affects the actions of amitriptyline. Diabetes was induced by a single intraperitoneal (i.p.) injection of STZ (50 mg/kg), and tactile allodynia was detected by application of von Frey filaments to the ventral surface of the hindpaw. Both systemic (0.5-2.0 mg/kg, i.p.) and peripheral (10-100 nmol, subcutaneously (s.c.)) administration of amitriptyline were found to produce increases in paw withdrawal thresholds, at higher doses. Coadministration of caffeine (5 mg/kg, i.p.; 1500 nmol, s.c.), at doses which produced no effect on its own, partially reversed systemic and local anti-allodynic effects of amitriptyline. These results indicate an anti-allodynic effect of both peripheral and systemic amitriptyline, and suggest the involvement of endogenous adenosine in the action of amitriptyline in this rat model of painful diabetic neuropathy. These data also suggest that topical application of tricyclic antidepressants may be useful in treating neuropathic pain in diabetics.
Asunto(s)
Adenosina/metabolismo , Amitriptilina/farmacología , Analgésicos/farmacología , Neuropatías Diabéticas/tratamiento farmacológico , Hiperalgesia/tratamiento farmacológico , Neuralgia/tratamiento farmacológico , Nociceptores/efectos de los fármacos , Nervios Periféricos/efectos de los fármacos , Animales , Antidepresivos Tricíclicos/farmacología , Cafeína/farmacología , Diabetes Mellitus Experimental/complicaciones , Neuropatías Diabéticas/metabolismo , Neuropatías Diabéticas/fisiopatología , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas/fisiología , Femenino , Hiperalgesia/metabolismo , Hiperalgesia/fisiopatología , Neuralgia/metabolismo , Neuralgia/fisiopatología , Nociceptores/metabolismo , Nociceptores/fisiopatología , Dimensión del Dolor/efectos de los fármacos , Umbral del Dolor/efectos de los fármacos , Umbral del Dolor/fisiología , Nervios Periféricos/metabolismo , Nervios Periféricos/fisiopatología , Inhibidores de Fosfodiesterasa/farmacología , Estimulación Física , Ratas , Ratas Sprague-DawleyRESUMEN
The response to opioids is reduced in neuropathic pain states. We examined the effect of the combination of morphine (0.1 mg/kg) and magnesium sulfate (125 mg/kg) on behavioral signs of neuropathic pain in spinal nerve ligated rats. Administered alone, neither drug produced any effect, but the combination exerted a significant anti-allodynic effect, which was partially reversed by naloxone. These results suggest that combining low doses of magnesium sulfate with opiates might be an alternative in treating neuropathic pain, with reduced risk of side effects.