Chronic Pain - Andreas S. Beutler

Cancer Pain

Chronic pain affects >60 percent of patients with cancer. Opioids in the class of morphine are the cornerstone of treatment. While adoption of this treatment approach has improved results, it fails in a significant number of patients. Recent studies report failure rates of 12 to 66 percent for medical pain therapy. Public interest in this health issue is considerable. "Pain Control in Advanced Cancer" was ranked among the top 20 health care priorities by the Institute of Medicine in the 2003 report "Priority Areas for National Action". Rodent model studies performed by other groups suggest that cancer pain might respond differently to analgesic therapies than other forms of chronic pain.

Laboratory research performed in our laboratory pursues the long-term goal of developing new analgesic treatment options for patients suffering from cancer pain.

Opioid Analgesics, the Standard-of-Care for Severe Pain, are Effective but Limited by Side-Effects

Opioid drugs like morphine are the mainstay for the treatment of most severe chronic pain states and their increased use has generally improved outcomes. However, opioids fail in a significant number of patients due to side-effects. Recent studies in cancer pain patients report failure rates of 12 to 66 percent for medical pain therapy. To elucidate causes of pain treatment failure, Weiss et al. studied the attitude of patients with severe pain (including cancer- and non-cancer pain states) towards their prescribed opioid doses. Of 514 patients treated for pain, 73 percent experienced moderate to severe pain. Yet, 60 percent of this group (i.e. those with unrelieved pain) did not wish to increase their opioid dose. 10 percent even wished to reduce it. Major reasons given by patients for not wanting additional therapy with opioids were the mental side effects (sedation, cognitive failure, hallucinations) as well as the physical side effects (constipation, nausea) at the prescribed dose level. A "Clinical Crossroads" discussion presented the dilemma in the words of a 44-year old woman with lung cancer: "So the biggest trade-off is that I'm in pain in order to stay lucid. I want to be awake and know everything that's going on, for as long as humanly possible. I do not want to die in pain. I do not want to be in pain. But I want to know what is going on around me." Prepro-β-endorphin (ppβEP) is a therapeutic gene developed in our laboratory, which harnesses the therapeutic potency of opioids while reducing opioid side effects through superior drug delivery (using gene vectors) as shown by our recent work.

Gene therapy for pain using Adeno-Associated Virus (AAV) is a novel strategy developed in our laboratory, which — we hope — will become an option for patients in the future. Gene therapy is currently under pre-clinical development in our group.

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