Neuropathic pain may be effectively relieved by electric stimulation of the spinal cord (SCS). However, the underlying mechanisms for the ensuing pain relief are poorly understood. In a rat model of neuropathy displaying hypersensitivity to innocuous tactile stimuli, (allodynia), we have earlier demonstrated that SCS may normalise withdrawal response thresholds. In the present study, using microdialysis, it is shown that SCS induces a decreased release of the dorsal horn excitatory amino acids (EAA), glutamate and aspartate, concomitant with an increase of the GABA release. Local perfusion with a GABA(B)-receptor antagonist in the dorsal horn transiently abolishes the SCS-induced suppression of the EAA release. Thus, the effect of SCS on neuropathic pain and allodynia may be due to an activation of local GABAergic mechanisms inhibiting the EAA release which is chronically elevated in such conditions.

Our results indicate that the development of allodynia, a common symptom in neuropathic pain states, may be linked to a decreased spinal release of GABA. We suggest that an SCS-induced release of GABA could be important for the suppression of allodynia observed in rats after SCS. Similar mechanisms could also be involved in the SCS-induced alleviation of pain in patients with peripheral neuropathy.

Skilled forelimb use was studied in rats with unilateral lesions of the sensorimotor cortex, the caudate-putamen, or the dopaminergic nigrostriatal bundle, in a task involving reaching for food. Limb preference and efficiency were evaluated, as well as the relationship between limb use, spontaneous, and methamphetamine-induced rotation bias, both preoperatively and postoperatively. To induce use of the nonpreferred limb, a bracelet, which prevented reaching but not other movements, was attached to the forearm of the preferred forelimb. Whereas small cortical lesions of the forepaw area of the sensorimotor cortex mildly influenced limb preference and use, larger lesions changed preference. Furthermore, medium-sized sensorimotor cortex lesions impaired contralateral limb use, although surprising recovery occurred on the forced tests with the bracelet. Large cortical lesions abolished effective reaching even on the forced tests. Impairments similar to those following sensorimotor cortex lesions were also obtained following small and large caudate-putamen lesions. By contrast, unilateral dopamine depletions not only blocked use of the limb contralateral to the depletion but also impaired use of the ipsilateral limb. There was recovery in use of the ipsilateral forelimb but not the contralateral forelimb. Correlational analysis showed a weak relation between methamphetamine-induced rotation and limb preference preoperatively but no significant relation between these two variables postoperatively. The similarity in the deficits following sensorimotor cortex lesions and basal ganglia lesions suggests that skilled forelimb use depends upon a shared neural organization within the two systems.

We describe a Bayesian inference scheme for quantifying the active physiology of neuronal ensembles using local field recordings of synaptic potentials. This entails the inversion of a generative neural mass model of steady-state spectral activity. The inversion uses Expectation Maximization (EM) to furnish the posterior probability of key synaptic parameters and the marginal likelihood of the model itself. The neural mass model embeds prior knowledge pertaining to both the anatomical [synaptic] circuitry and plausible trajectories of neuronal dynamics. This model comprises a population of excitatory pyramidal cells, under local interneuron inhibition and driving excitation from layer IV stellate cells. Under quasi-stationary assumptions, the model can predict the spectral profile of local field potentials (LFP). This means model parameters can be optimised given real electrophysiological observations. The validity of inferences about synaptic parameters is demonstrated using simulated data and experimental recordings from the medial prefrontal cortex of control and isolation-reared Wistar rats. Specifically, we examined the maximum a posteriori estimates of parameters describing synaptic function in the two groups and tested predictions derived from concomitant microdialysis measures. The modelling of the LFP recordings revealed (i) a sensitization of post-synaptic excitatory responses, particularly marked in pyramidal cells, in the medial prefrontal cortex of socially isolated rats and (ii) increased neuronal adaptation. These inferences were consistent with predictions derived from experimental microdialysis measures of extracellular glutamate levels.