diprenorphine and Stroke

Central neuropathic pain (CNP) is pain resulting from damage to the central nervous system. Up till now, it has not been possible to identify a common lesion or pharmacological deficit in these patients. This preliminary study in a group of patients with CNP with predominantly post-stroke pain, demonstrates that there is significantly less opioid receptor binding in a number of cortical and sub-cortical structures that are mostly, but not exclusively, within the medial pain system in patients compared to age-matched pain-free controls. The reductions in opioid receptor binding within the medial system were observed mainly in the dorsolateral (Brodman area 10) and anterior cingulate (Brodman area 24 with some extension into area 23) and insula cortices and the thalamus. There were also reductions in the lateral pain system within the inferior parietal cortex (Brodman area 40). These changes in binding could not be accounted for by the cerebral lesions shown by CT or MRI, which were outside the areas of reduced binding and the human pain system. To our knowledge this is the first systematic demonstration of a reduction in opioid receptor-binding capacity in neurones within the human nociceptive system in patients with CNP. This may be a key common factor resulting in undamped nociceptor activity within some of the structures that are predominantly within the medial nociceptive system. If confirmed, these findings may explain why certain patients with CNP require high doses of synthetic opiates to achieve optimum analgesia. The findings also raise the possibility of new pharmacological approaches to treatment.

Topics: Aged; Analgesics; Binding, Competitive; Cerebral Cortex; Diprenorphine; Down-Regulation; Drug Resistance; Female; Humans; Male; Middle Aged; Models, Neurological; Neural Pathways; Opioid Peptides; Pain, Intractable; Positron-Emission Tomography; Predictive Value of Tests; Radioligand Assay; Receptors, Opioid; Stroke; Thalamus

Based on concepts that endogenous opioids participate in neural transmission of pain, the present study in central poststroke pain (CPSP) patients investigated changes in opioid receptor (OR) binding in neural structures centrally involved in the processing of pain. Five patients with central pain after lesions in the brain stem, thalamus or parietal cortex and twelve healthy volunteers underwent a [11C]diprenorphine positron emission tomography study. Binding potentials were calculated using a reference region model in all subjects. Statistical parametric mapping was applied for t-statistical analysis on voxel-basis. Binding potential values for each individual were extracted from a volume of interest at each identified significant peak. Spectral analysis was applied for quantification of global values. Significant regional reduced 11C-diprenorphine binding (corrected for multiple tests) was detected in contralateral thalamus, parietal, secondary somatosensory, insular and lateral prefrontal cortices, and along the midline in anterior cingulate, posterior cingulate and midbrain gray matter. Individual extracted binding values disclosed a reduced binding in these regions in all patients independent from the particular lesion site. The poststroke pain syndrome is associated with a characteristic pattern of reduced OR binding within the neural circuitry processing pain. It is suggested that an imbalance of excitatory-inhibitory mechanisms in certain brain structures, as evidenced in decreased [11C]diprenorphine binding, is one of the causes or the consequences of poststroke pain.

Topics: Aged; Brain Mapping; Carbon Radioisotopes; Central Nervous System; Diprenorphine; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Pain; Radiopharmaceuticals; Receptors, Opioid; Stroke; Tomography, Emission-Computed