Cerebral decreases in opioid receptor binding in patients with central neuropathic pain measured by [11C]diprenorphine binding and PET

Eur J Pain. 2004 Oct;8(5):479-85. doi: 10.1016/j.ejpain.2003.11.017.

Abstract

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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Analgesics / pharmacology
  • Binding, Competitive
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / physiopathology*
  • Diprenorphine / metabolism
  • Diprenorphine / pharmacokinetics
  • Down-Regulation / physiology*
  • Drug Resistance / physiology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Models, Neurological
  • Neural Pathways / diagnostic imaging
  • Neural Pathways / metabolism
  • Neural Pathways / physiopathology
  • Opioid Peptides / metabolism
  • Pain, Intractable / diagnostic imaging
  • Pain, Intractable / etiology
  • Pain, Intractable / physiopathology*
  • Positron-Emission Tomography
  • Predictive Value of Tests
  • Radioligand Assay
  • Receptors, Opioid / metabolism*
  • Stroke / complications*
  • Thalamus / diagnostic imaging
  • Thalamus / metabolism
  • Thalamus / physiopathology

Substances

  • Analgesics
  • Opioid Peptides
  • Receptors, Opioid
  • Diprenorphine