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Chronic 'pathological' pain is sustained by mechanisms of peripheral and central sensitization, which are being increasingly investigated at the molecular and cellular levels. The molecular determinants of nociceptive sensitization are natural targets for potential analgesic drugs used in the treatment of different forms of pain. Most of these determinants are common to all forms of chronic pain, and it is therefore not surprising that drugs specifically targeted for the treatment of neuropathic pain are effective in relieving nociceptive inflammatory pain and vice versa. The molecular mechanisms of sensitization that occur in peripheral nociceptors and the dorsal horns of the spinal cord are putative targets for context-dependent drugs, i.e. drugs that are able to discriminate between 'normal' and 'pathological' pain transmission. Among these, pregabalin and gabapentin bind to the alpha(2)delta subunit of voltage-sensitive Ca2+ channels, which sustain the enhanced release of pain transmitters at the synapses between primary afferent fibres and second-order sensory neurons under conditions of chronic pain. Pregabalin in particular represents a remarkable example of a context-dependent analgesic drug that acts at a critical step of nociceptive sensitization. Preclinical and clinical data suggest that pregabalin is more than a structural and functional analogue of gabapentin and may be effective in the treatment of nociceptive inflammatory pain that is resistant to gabapentin.

The effects of chronic haloperidol and sulpiride treatment on nigral GABA content were investigated in rats. Chronic sulpiride treatment is capable of inducing an increase in nigral GABA content whilst no significant effect is observed following chronic haloperidol treatment at the doses used. The different effects of haloperidol and sulpiride on nigral GABA content were related to the different neuropharmacological spectrum of the two drugs.

Nigral and striatal GABA contents were assayed in male rats treated chronically with haloperidol or sulpiride, two dopamine-receptor blocking agents that have different neuropharmacological spectra in regard to their biochemical, behavioural, and clinical properties. No great difference was observed between the chronic effects of haloperidol and sulpiride on nigral and striatal GABA content. However, low doses (30 micrograms/kg, intraperitoneally) of the dopamine-receptor agonist apomorphine, injected 12 h after the discontinuation of chronic haloperidol or chronic sulpiride treatment, induced opposite changes in nigral GABA levels suggesting the existence of a different "status" of the dopamine receptors during the 12 h-period following the withdrawal of haloperidol or sulpiride.