Antinociceptive action of oxytocin involves inhibition of potassium channel currents in lamina II neurons of the rat spinal cord

<p>Abstract</p> <p>Background</p> <p>Growing evidence in the literature shows that oxytocin (OT) has a strong spinal anti-nociceptive action. Oxytocinergic axons originating from a subpopulation of paraventricular hypothalamic neurons establish synaptic contacts with lamina II interneurons but little is known about the functional role of OT with respect to neuronal firing and excitability.</p> <p>Results</p> <p>Using the patch-clamp technique, we have recorded lamina II interneurons in acute transverse lumbar spinal cord slices of rats (15 to 30 days old) and analyzed the OT effects on action potential firing ability. In the current clamp mode, we found that bath application of a selective OT-receptor agonist (TGOT) reduced firing in the majority of lamina II interneurons exhibiting a bursting firing profile, but never in those exhibiting a single spike discharge upon depolarization. Interestingly, OT-induced reduction in spike frequency and increase of firing threshold were often observed, leading to a conversion of the firing profile from repetitive and delayed profiles into phasic ones and sometimes further into single spike profile. The observed effects following OT-receptor activation were completely abolished when the OT-receptor agonist was co-applied with a selective OT-receptor antagonist. In current and voltage clamp modes, we show that these changes in firing are strongly controlled by voltage-gated potassium currents. More precisely, transient I_Acurrents and delayed-rectifier currents were reduced in amplitude and transient I_Acurrent was predominantly inactivated after OT bath application.</p> <p>Conclusion</p> <p>This effect of OT on the firing profile of lamina II neurons is in good agreement with the antinociceptive and analgesic properties of OT described <it>in vivo</it>.</p

Gabapentin for overactive bladder and nocturia after anticholinergic failure

INTRODUCTION: We reviewed our experience with the use of gabapentin to treat symptoms of overactive bladder (OAB) and nocturia in patients who have failed conventional anticholinergic therapy. METHODS: Thirty-one patients referred to us with refractory (OAB) and/or nocturia were treated with oral gabapentin. All the patients had tried or remained on antimuscarinic drugs during treatment. Twenty-four of 31 complained of bothersome symptoms during day and night and the other seven had primary complaints of nocturia. Initial gabapentin doses ranged from 100-300 mg at bedtime. Dose was slowly titrated up to 3,000 mg based on patients' symptomatology and tolerability. RESULTS:The mean age was 51 years old (range 27-78). There were 13 men and 18 women. The median steady state dose chosen by the patient after initial titration was 600 mg/day. Fourteen of 31 patients reported subjective improvement of their frequency and 8 have been on the medication for over 12 months with persistent efficacy. For the 14 improved patients, mean frequency/24 hours decreased from 14.1 &plusmn; 2.2 to10.0 + 2.1. Three patients with primary nocturia reported improvement from a mean of 4.0 &plusmn; 1.3 to 1.0 &plusmn; 0.3 episodes/night. Six patients stopped taking the drug within one month due to side effects mostly described as drowsiness or lethargy. CONCLUSION: Fourteen of 31 patients with refractory (OAB) and nocturia improved with oral gabapentin. Gabapentin was generally well tolerated and can be considered in selective patients when conventional modalities have failed

Warm-coding deficits and aberrant inflammatory pain in mice lacking P2X3 receptors

ATP activates damage-sensing neurons (nociceptors) and can evoke a sensation of pain(1). The ATP receptor P2X(3) is selectively expressed by nociceptors(2,3) and is one of seven ATP-gated, cation-selective ion channels(4-6). Here we demonstrate that ablation of the P2X(3) gene results in the loss of rapidly desensitizing ATP-gated cation currents in dorsal root ganglion neurons, and that the responses of nodose ganglion neurons to ATP show altered kinetics and pharmacology resulting from the loss of expression of P2X(2/3) heteromultimers. Null mutants have normal sensorimotor function. Behavioural responses to noxious mechanical and thermal stimuli are also normal, although formalin-induced pain behaviour is reduced. In contrast, deletion of the P2X(3) receptor causes enhanced thermal hyperalgesia in chronic inflammation. Notably, although dorsal-horn neuronal responses to mechanical and noxious heat application are normal, P2X(3)-null mice are unable to code the intensity of non-noxious 'warming' stimuli