Pain/Grief/ Depression, Fatigue Studies

Although morphine has been the gold-standard treatment for postoperative and chronic cancer pain for two centuries, a growing body of evidence is showing that opiate-based painkillers can stimulate the growth and spread of cancer cells. Two new studies advance that argument and demonstrate how shielding lung cancer cells from opiates reduces cell proliferation, invasion and migration in both cell-culture and mouse models.

The reports--presented November 18, 2009, at "Molecular Targets and Cancer Therapeutics," a joint meeting in Boston of the American Association for Cancer Research, the National Cancer Institute, and the European Organization for Research and Treatment of Cancer--highlight the mu opiate receptor, where morphine works, as a potential therapeutic target.

"If confirmed clinically, this could change how we do surgical anesthesia for our cancer patients," said Patrick A. Singleton, PhD, assistant professor of medicine at the University of Chicago Medical Center and principal author of both studies. "It also suggests potential new applications for this novel class of drugs which should be explored."

The proposition that opiates influence cancer recurrence, prompted by several unrelated clinical and laboratory studies, has gradually gained support. It started with a 2002 palliative-care trial in which patients who received spinal rather than systemic pain relief survived longer. Soon after that, Singleton's colleague, anesthesiologist Jonathan Moss, noticed that several cancer patients receiving a selective opiate blocker in a compassionate-use protocol lived longer than expected. Two recent retrospective studies found that breast and prostate cancer patients who received regional rather than general anesthesia had fewer recurrences.

In February, 2009, the Anesthesia Patient Safety Foundation highlighted the issue.

SOURCE: Pain Foundation

12/21/07 FDA Medwatch ALERT:

FDA issued an update that highlights important information on appropriate prescribing, dose selection, and the safe use of the fentanyl transdermal system (patch). FDA previously issued a Public Health Advisory and Information for Healthcare Professionals in July 2005 regarding the appropriate and safe use of the transdermal system. However, the Agency continues to receive reports of death and life-threatening adverse events related to fentanyl overdose that have occurred when the fentanyl patch was used to treat pain in opioid-naive patients and when opioid-tolerant patients have applied more patches than prescribed, changed the patch too frequently, and exposed the patch to a heat source. The fentanyl patch is only indicated for use in patients with persistent, moderate to severe chronic pain who have been taking a regular, daily, around-the-clock narcotic pain medicine for longer than a week and are considered to be opioid-tolerant.

Patients must avoid exposing the patch to excessive heat as this promotes the release of fentanyl from the patch and increases the absorption of fentanyl through the skin which can result in fatal overdose. Directions for prescribing and using the fentanyl patch must be followed exactly to prevent death or other serious side effects from fentanyl overdose.

Read the complete 2007 MedWatch Safety Summary including a link to the FDA Public Health Advisory and Information for Healthcare Professionals Sheet regarding this issue at:

Morphine Alternative for Pain Control

All pain is apparently not created equal and, according to University of California, San Francisco researchers, some people may be better served if they use a new combination of older drugs to control their pain.

``The combination of two 'old' narcotics...which have fewer side effects and less abuse potential than the currently used narcotics (such as morphine and fentanyl), may be very useful in the treatment of moderate to severe pain,'' senior author Dr. Jon D. Levine told Reuters Health.

Levine and his colleagues have been exploring a class of painkillers called kappa-opioids, which in low to moderate doses have fewer side effects and are less likely to be habit-forming than morphine. An older family of drugs, kappa-opioids are thought to be relatively ineffective painkillers. In fact, one particular kappa-opioid--nalbuphine--actually increases pain in men, when given in low doses, and has no effect on pain in women.

However, the investigators found that the drug does appear to be an effective painkiller in both men and women when given in combination with another medication, known as naloxone, according to a report in the June 14th issue of the Journal of Pain. In the study of 56 patients undergoing dental surgery, adding naloxone--a drug that blocks opioids--to nalbuphine relieved pain effectively in both men and women.

The combination may offer an alternative when it comes to relieving moderate to severe pain, according to the report. And the study adds to previous research that has found that men and women experience pain differently, and thus may respond differently to painkillers.

``I think that the kappa-opioid analgesics currently available have two mechanisms of action, one that decreases pain, and one that makes it worse,'' Levine said. In men, apparently, there is a predominance of the pain-worsening mechanism.

Naloxone in combination with nalbuphine is able to knock out the pain-enhancing effect in both males and females, and eliminate the gender difference seen with the kappa-opioid, Levine explained.

Asked about how such a gender difference might have arisen, Levine speculated that it may be due to the different types of pain historically experienced by men and women. He noted that women need to cope with the pain of childbearing while men have typically been exposed to more injury-related pain.

``It may be that there are multiple mechanisms in the brain for dealing with different aspects of pain and that males and females make differential use of these multiple (the body's own) pain control circuits,'' he added.

The team's next step will be to find out who can benefit the most from the drug combination.

There ``are a lot of other pain syndromes in which we would like to test this therapy,'' Levine noted. ``We also very much want to figure out the exact mechanism for the pain enhancing component of the effect of kappa-opiates (narcotics) that appears to be much greater in males.''

SOURCE: Journal of Pain 2000;1:122-127.

Thanks to Penny Stern, MD, Reuters Health

ALSO SEE: NON-Toxic Methods for 'natural' pain, fatigue relief in Studies section.

Depression Issues

Br J Cancer, 7/02

Foods/Nutrients for Grieving, Depression, Stress
Unstuck: Your Guide to the Seven Stage Journey Out of Depression
Redheads Need More Anesthesia

University of Lousiville study, 10/02

Redheads Respond to Pain Killers Better
Endogenous Opioid Function Differs Men/Women
For Neuropathy: Possibilities

Various sources

Systemic Artemin & Neuropathy
Treatment & Care of Neurotoxicity
Oral Cannabinoids: Neuropathic Pain
Ascorbic Acid for Charcot-Marie-Tooth Disease
Urea Cream Used w/Hand Foot Syndrome:Capecitabine
Vit E Neuroprotective w/Cisplatin
Acetyl-L Carnitine Improves Diabetic Neuropathy
Acupuncture Reduces Pain, Neuropathy
Anodyne Therapy for Neuropathy
Treatment of (alcoholic) Polyneuropathy w/ Vit B Complex
Oral Glutamine Effective Prevents Oxaliplatin-Induced Neuropathy Colorectal Ca Pts
Divorce/Widowhood on Cancer Risk

Cancer Epi Bio & Prev,9/03

Mourners' Rights

Studies, articles, etc.

FDA Letter to Amgen
Newsletter on NeoRecormon
Fatigue & Impact on Quality of Life
Acupuncture for Postchemo Fatigue
L-carnitine Supplmntatn in Ca Pts w/Fatigue
Polarity Therapy for Fatigue: Pilot Study
Home-based Walking Reduces Fatigue
Moderate Exercise during Radiation Tx Reduces Fatigue
Yoga for Fatigue After Breast Ca Treatment

Studies, articles, LINKS

Adverse Effects of Morphine-Strategies
Giving Patients Better Ways to Talk About Pain
Cancer Pain Management-Decision Trial
Use of Methadone for Cancer Pain
Pain Needs Relief - Study Demonstrates
Quebec: Issues in Cancer Pain Mgment
Onco Nurses Evidence-Based Mgmnt:PAIN
Natural Pain Reduction Methods
PAIN:Chat Info
Pain Relief Ball after Hysterectomy/C-section
Implantable Pain Pumps/QOL
How Arnica Works - Herbal Remedy for Aches & Bruises
Pain w/Lumpectomy & RTx
Synthetic Sea Snail Venom:PAIN relief
NCPB Improves Pain Relief BUT Not QoL/Survival
Canadian Co Tests Puffer Fish Drug for Pain
Drug Enforcement Administration
Cancer Pain Assessment Tool in Korea; Validation
Pain and Pain Treatment
Pediatric Pain & Acupuncture
When Should we Define the Response Rates:Treatment of Bone Mets by Palliative RadiotTx?
Chronic pain & Inadequate Blood levels of vitamin D
PAIN: Recommendations of a task group Great Britain/Ireland
Brain Scans Show Pts in Minimally Conscious State Feel Pain
On Pain Issues - article by Kenneth Schueler
Mgment of Opioid-Induced GI Effects

Pharmacotherapy, 2002 Abstract & Intro

Pathophysiology of Opioid-Induced Nausea
Summary, Drugs for Treating Nausea, Constipation
References Opioid and GI Effects
Ultra Low-dose Naltrexone:Prevent Opioid Trouble
Pain Management is Often Inadequate: Pharmacists View
Phantom Pain After Mastectomy

J Pain, 2/04

Venlafaxine X R & Prevntn Postmastectomy Pain
Marijuana  & Pain Relief

Study 8/00 show may work when morphine fails with spine/nerve injuries (possibly neuropathy from taxanes?)

Management of Pain: Systemic Review
MS & Cannabis-Pain Relief
Analgesic Effect of Synthetic Cannabinoid CT-3
Singer Melissa Etheridge Says Med MJ Helped Chemo
Cannabinoids: Pain Relief, REVIEW
Synthetic Cannabinoid Nabilone Improves Pain & Symptom Mgmnt in ca pts
Medical MJ reduces Post-op Pain
Med MJ and Peripheral Neuropathy

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