Clinical research in pain management at Memorial Sloan-Kettering Cancer Center involves specialists in the fields of neurology, anesthesiology, psychiatry and psychology, and pharmacology, among others. Our work is built on a solid scientific foundation of the study of the nature of pain and the characteristics of traditional and novel methods of pain relief.
Specific areas of focus include the development of better analgesics for pain, the study of the neurological and molecular basis of pain, and the creation of better methods to enable patients to describe and rate their levels of pain.
Among our recent research accomplishments:
- Our investigators are collaborating with those from other institutions to understand the genetic basis for variability of analgesic responsiveness in cancer pain syndromes. Researchers are analyzing blood samples of patients with post-operative pain to correlate SNP (or other genetic) differences in the opiate receptor gene with the relative efficacy of specific opioids. The hypothesis is that genetic signatures might guide clinicians in tailoring therapy to individuals. Three manuscripts are being prepared to describe the correlations between analgesia, dose of self-administered morphine, and opioid-related side effects, as well as correlation between these clinical data and plasma levels of morphine, M-3-G, M-6-G, and patient's age and renal function. Neuropsychopharmacol 2005;30:417-422. [PubMed Abstract]
- We have isolated and cloned more than 40 splice variants of the mu opioid receptorMOR-1 from mice, rats and humans. Most of these variants have no sequence variation in the opioid binding pocket and therefore will show similar affinities with specific opioid ligands. Nevertheless, the splice variants do show differences of rank-order potencies and intrinsic activities for various opioid ligands. The implication is that basing criteria for the discovery of more selective mu opioids mainly on enhanced receptor affinity (the traditional criterion of medicinal chemists) may be shortsighted, and a fuller accounting of a candidate drug's therapeutic potential may need to take intrinsic activity into account. Neurosci 2005;133:209-220. [PubMed Abstract]
- We are studying d-methadone, which may be uniquely advantageous in the treatment of neuropathic pain in patients with chronic cancer pain. D-methadone has been noted to antagonize the receptors critical to the development and maintenance of neuropathic pain states, while not causing problematic opiate-related side effects or addiction.
- Memorial Sloan-Kettering Cancer Center investigators have demonstrated a profound synergy for analgesia, but not for gastrointestinal motility inhibition, when morphine and methadone are co-administered systemically to mice. In collaboration with the Department of Urology, this study explores the implications of this finding for patients suffering from postoperative pain. Optimal pain control is being gauged by patient reports. Assuming that a synergistic analgesic effect of morphine and methadone is suggested, a phase III study will be implemented. The ultimate goal is to ascertain whether patients can achieve good pain control with lower dosages of morphine, thus minimizing side effects and addictive potential.
- Our investigators have sought to identify key molecules involved in pain sensation. They have successfully blocked the NMDA receptor, an important factor in the mediation of pain sensation in the spinal cord. This technique offers a method for the study of pain pathways on a molecular level and will aid in the development of medications with fewer side effects.
- Following a pilot trial showing the feasibility of using acupuncture for post-thoracotomy pain, a placebo-controlled randomized controlled trial is underway to compare epidural analgesia with and without acupuncture for post-thoracotomy pain relief. Our researchers are also assessing the use of acupuncture for pain and neck dysfunction following head and neck surgery. BMC Anesthesiol 2006;6:5. [PubMed Abstract]
